... Services HIV Overview What is a Preventive HIV Vaccine? (Last updated 2/20/2017; last reviewed 2/ ... preventive HIV vaccine. What is a preventive HIV vaccine? A preventive HIV vaccine is given to people ...
McNicholl, Janet M.
ABSTRACT Biomedical preventions for HIV, such as vaccines, microbicides or pre-exposure prophylaxis (PrEP) with antiretroviral drugs, can each only partially prevent HIV-1 infection in most human trials. Oral PrEP is now FDA approved for HIV-prevention in high risk groups, but partial adherence reduces efficacy. If combined as biomedical preventions (CBP) an HIV vaccine could provide protection when PrEP adherence is low and PrEP could prevent vaccine breakthroughs. Other types of PrEP or microbicides may also be partially protective. When licensed, first generation HIV vaccines are likely to be partially effective. Individuals at risk for HIV may receive an HIV vaccine combined with other biomedical preventions, in series or in parallel, in clinical trials or as part of standard of care, with the goal of maximally increasing HIV prevention. In human studies, it is challenging to determine which preventions are best combined, how they interact and how effective they are. Animal models can determine CBP efficacy, whether additive or synergistic, the efficacy of different products and combinations, dose, timing and mechanisms. CBP studies in macaques have shown that partially or minimally effective candidate HIV vaccines combined with partially effective oral PrEP, vaginal PrEP or microbicide generally provided greater protection than either prevention alone against SIV or SHIV challenges. Since human CBP trials will be complex, animal models can guide their design, sample size, endpoints, correlates and surrogates of protection. This review focuses on animal studies and human models of CBP and discusses implications for HIV prevention. PMID:27679928
Lindegger, Graham; Quayle, Michael; Ndlovu, Moses
This study forms part of the preparation of communities for HIV-preventive vaccine trials in South Africa. On the basis of the assumption that attitudes to any HIV vaccine or vaccine trials will partly be influenced by experiences of vaccination in general, this study aimed to investigate knowledge of, attitudes to, and experiences of vaccination…
Phanuphak, Nittaya; Lo, Ying-Ru; Shao, Yiming; Solomon, Sunil Suhas; O'Connell, Robert J.; Tovanabutra, Sodsai; Chang, David; Kim, Jerome H.
Abstract An overall decrease of HIV prevalence is now observed in several key Asian countries due to effective prevention programs. The decrease in HIV prevalence and incidence may further improve with the scale-up of combination prevention interventions. The implementation of future prevention trials then faces important challenges. The opportunity to identify heterosexual populations at high risk such as female sex workers may rapidly wane. With unabating HIV epidemics among men who have sex with men (MSM) and transgender (TG) populations, an effective vaccine would likely be the only option to turn the epidemic. It is more likely that efficacy trials will occur among MSM and TG because their higher HIV incidence permits smaller and less costly trials. The constantly evolving patterns of HIV-1 diversity in the region suggest close monitoring of the molecular HIV epidemic in potential target populations for HIV vaccine efficacy trials. CRF01_AE remains predominant in southeast Asian countries and MSM populations in China. This relatively steady pattern is conducive to regional efficacy trials, and as efficacy warrants, to regional licensure. While vaccines inducing nonneutralizing antibodies have promise against HIV acquisition, vaccines designed to induce broadly neutralizing antibodies and cell-mediated immune responses of greater breadth and depth in the mucosal compartments should be considered for testing in MSM and TG. The rationale and design of efficacy trials of combination prevention modalities such as HIV vaccine and preexposure prophylaxis (PrEP) remain hypothetical, require high adherence to PrEP, are more costly, and present new regulatory challenges. The prioritization of prevention interventions should be driven by the HIV epidemic and decided by the country-specific health and regulatory authorities. Modeling the impact and cost–benefit may help this decision process. PMID:26107771
Voronin, Yegor; Phogat, Sanjay
The symposium "HIV/AIDS: Vaccines and Alternate Strategies for Treatment and Prevention" brought together HIV vaccine researchers to discuss the latest developments in the field. From basic discoveries in virus diversity and mechanisms of neutralization by antibodies to nonhuman primate research and clinical trials of vaccine candidates in volunteers, scientists are making great strides in understanding the mechanisms that may protect against HIV and pathways to achieve this protection through vaccination.
Nikolic, Damjan S; Piguet, Vincent
HIV-1, herpes simplex virus type 2 (HSV-2), and human papillomavirus (HPV), among other sexually transmitted infections, represent a major burden for global health. Initial insights into the mucosal transmission of these viral pathogens have raised optimism with regard to the rapid generation of protective vaccines. Nevertheless, setbacks for HIV-1 and HSV-2 vaccines have seriously challenged the initial enthusiasm. Recently, two new vaccines that efficiently prevented HPV infection have renewed the hope that vaccinal prevention of viral mucosal sexually transmitted infections is possible. HIV-1 and HSV-2 differ from HPV, and each virus needs to be tackled with a distinct approach. However, vaccines are not the only possible answer. Topically applied agents (microbicides) are an attractive alternative in the prevention of HIV-1 and HSV-2 mucosal transmission. Progress in understanding the mechanisms of genital transmission of HIV-1 and HSV-2 is required for successful vaccine or microbicide candidates to emerge from current approaches.
Sticchi, Laura; Bruzzone, Bianca; Caligiuri, Patrizia; Rappazzo, Emanuela; Lo Casto, Michele; De Hoffer, Laura; Gustinetti, Giulia; Viscoli, Claudio; Di Biagio, Antonio
Background Even in the era of highly active antiretroviral therapy (HAART), HIV-infected subjects are at higher risk of complications from vaccine-preventable diseases than those uninfected. The current international guidelines strongly recommend that these patients should receive all the routine childhood vaccinations. Although these children represent an appropriate target for immunization, the available data indicate suboptimal coverage rates. Methods To evaluate seroprotection/seropositivity rates and vaccination coverage against the common vaccine-preventable diseases, all patients with vertically transmitted HIV-1 infection who attended San Martino Hospital were enrolled. Blood samples were collected for testing antibodies against diphtheria, tetanus, hepatitis A and B viruses by Enzyme-Linked ImmunoSorbent Assay and polioviruses by microneutralization test. In order to assess immunization coverage, retrospectively was recorded the vaccination history collecting data from Regional Immunization Database. Results A total of 39 perinatally HIV-1 infected patients were included in the study. At the time of serum was obtained, the mean age was 18,1 years (range: 6–28). The median CD4+ T-lymphocyte count was 702 cells/mm3 (2–1476 cells/mm3). Twenty-nine (74.4%) patients were found with HIV RNA load < 50 copies/mL. The proportion of subjects with protective anti-tetanus and anti-HBs were 43.6% and 30.8%, respectively. Seroprotection rates about 20% against rubella and measles were found, less than 20% against all the other antigens investigated. In particular, all patients resulted susceptible to mumps. High immunization rates were observed for polio and HBV (100% and 92.3%, respectively) and suboptimal for diphtheria-tetanus (84.6%). For the other recommended vaccines the rates were generally low. None of the patients received varicella vaccine doses. Conclusions As in the HAART era the vertically acquired HIV infection has become a chronic treatable disease
Bailey, Theodore C.; Sugarman, Jeremy
The advent of pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) as means of HIV prevention raises issues of justice concerning how most fairly and equitably to apportion resources in support of the burgeoning variety of established HIV treatment and prevention measures and further HIV research, including HIV vaccine research. We apply contemporary approaches to social justice to assess the ethical justification for allocating resources in support of HIV vaccine research given competing priorities to support broad implementation of HIV treatment and prevention measures, including TasP and PrEP. We argue that there is prima facie reason to believe that a safe and effective preventive HIV vaccine would offer a distinct set of ethically significant benefits not provided by current HIV treatment or prevention methods. It is thereby possible to justify continued support for HIV vaccine research despite tension with priorities for treatment, prevention, and other research. We then consider a counter-argument to such a justification based on the uncertainty of successfully developing a safe and effective preventive HIV vaccine. Finally, we discuss how HIV vaccine research might now be ethically designed and conducted given the new preventive options of TasP and PrEP, focusing on the ethically appropriate standard of prevention for HIV vaccine trials. PMID:24033297
Bailey, Theodore C; Sugarman, Jeremy
The advent of pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) as means of HIV prevention raises issues of justice concerning how most fairly and equitably to apportion resources in support of the burgeoning variety of established HIV treatment and prevention measures and further HIV research, including HIV vaccine research. We apply contemporary approaches to social justice to assess the ethical justification for allocating resources in support of HIV vaccine research given competing priorities to support broad implementation of HIV treatment and prevention measures, including TasP and PrEP. We argue that there is prima facie reason to believe that a safe and effective preventive HIV vaccine would offer a distinct set of ethically significant benefits not provided by current HIV treatment or prevention methods. It is thereby possible to justify continued support for HIV vaccine research despite tension with priorities for treatment, prevention, and other research. We then consider a counter-argument to such a justification based on the uncertainty of successfully developing a safe and effective preventive HIV vaccine. Finally, we discuss how HIV vaccine research might now be ethically designed and conducted given the new preventive options of TasP and PrEP, focusing on the ethically appropriate standard of prevention for HIV vaccine trials.
... NIAID). /* // ** // */ Prevention Research Vaccines Microbicides Related Topics on AIDS.gov Clinical Trials Immune System 101 HIV Vaccine ... Be the Generation Last revised: 12/09/2016 AIDS.gov HIV/AIDS Basics • Federal Resources • Using New ...
Lally, Michelle; Goldsworthy, Richard; Sarr, Moussa; Kahn, Jessica; Brown, Larry; Peralta, Ligia; Zimet, Greg
Purpose Placebo and randomization are important concepts that must be understood before youth can safely participate in HIV vaccine studies or other biomedical trials for HIV prevention. These concepts are central to the phenomenon of preventive misconception which may be associated with an increase in risk behavior among study participants related to mistaken beliefs. Persuasive messaging, traditionally used in the field of marketing, could enhance educational efforts associated with randomized clinical trials. Methods Two educational brochures were designed to increase knowledge about HIV vaccine clinical trials via 1 and 2-sided persuasive messaging. Through the Adolescent Medicine Trials Network, 120 youth were enrolled, administered a mock HIV vaccine trial consent, and then randomized to receive either no supplemental information or one of the two brochures. Results The 2-sided brochure group in which common clinical trial misconceptions were acknowledgedand then refuted had significantly higher scores on knowledge of randomization and interpretation of side effects than the consent-only control group, and willingness to participate in an HIV vaccine trial was not decreased with the use of this brochure. Conclusion Two sided persuasive messaging improves understanding of the concepts of randomization and placebo among youth who would consider participating in an HIV vaccine trial. Further evaluation of this approach should be considered for at-risk youth participating in an actual trial of a biomedical intervention for HIV prevention. PMID:24613097
Harmon, Thomas; Guo, Wei; Stover, John; Wu, Zunyou; Kaufman, Joan; Schneider, Kammerle; Liu, Li; Feng, Liao; Schwartländer, Bernard
China's commitment to implementing established and emerging HIV/AIDS prevention and control strategies has led to substantial gains in terms of access to antiretroviral treatment and prevention services, but the evolving and multifaceted HIV/AIDS epidemic in China highlights the challenges of maintaining that response. This study presents modeling results exploring the potential impact of HIV vaccines in the Chinese context at varying efficacy and coverage rates, while further exploring the potential implications of vaccination programs aimed at reaching populations at highest risk of HIV infection. A preventive HIV vaccine would add a powerful tool to China's response, even if not 100% efficacious or available to the full population.
Tan, Hyon-Xhi; Kent, Stephen J; De Rose, Robert
HIV is primarily transmitted to women via the cervicovaginal mucosa, with the infection remaining localized for several days prior to systemic dissemination and irreversible damage to the immune system. The early phase during which HIV infection is localized and exhibits little or no viral diversity presents a vantage point for HIV vaccines that stimulate T-cell mediated clearance. CD(8+) resident memory T-cells (TRM) are positioned at mucosal entry sites and are established upon resolution of infection by mucosal pathogens. TRM cells are long-lived and locally patrol mucosal tissues. Upon antigenic reactivation, the sentinel-like functions of TRM cells mediate rapid clearance of subsequent infection by recruitment of additional immune cells from circulation and initiate a tissue-wide antiviral state, thus preventing the recurrence of disease. These properties are ideally suited for an HIV vaccine aimed at halting the infection cycle of HIV during the earliest phases. In this review, we summarize recent vaccine developments from parallel research areas incorporating the use of live mucosal vectors complemented with chemokine-regulating compounds, which can induce the seeding of the vaginal mucosa with TRM cells. We present the proposition that similar novel vaccine regimens can be translated into approaches for future HIV vaccines aimed at inducing heightened immunity in vaginal tissues against HIV.
Nearly everywhere that AIDS has been found, HIV infection is fast spreading. No one is known to have recovered from HIV infection. There is no vaccine to cure AIDS (Population Reports, 1989 and The Hindu, dated 9.3.2000). Until a cure or vaccine for HIV infection is found, the only way to prevent the spread of the disease is by changing people's behaviour through AIDS education programmes (Population Reports, 1986). Many national governments are using broadcast, print media, personal contact, counselling methods, etc., to educate people on AIDS and safer sex. Thus, the best vaccine is the 'Social Vaccine.' Social vaccine involves spreading education on how to protect oneself, hundred percent condom use, and changing sexual behaviour. In fact, the social vaccine was so successful in Thailand that the infection rate has come down by 50 per cent (The Hindu, dated 9.3.2000). Truck drivers, prostitutes, and young adults are considered high risk groups for HIV/AIDS in India. An action research study was conducted in Chittoor District of Andhra Pradesh (India) among truck drivers. As part of this study, different strategies, namely mass media, personal contact, group discussion, folk media, and counselling, were adopted to provide AIDS education, to encourage increase in condom use for safer sex, and bring changes in their sexual behaviour. The strategies adopted in this study greatly enhanced the knowledge of the truck drivers on AIDS, changed their attitudes on sex, increased the use of condoms, and modified their sexual behaviour. Thus, the social vaccine would help spread education on AIDS, bring changes in the sexual behaviour of the people, increase condom use, and thus help to prevent the AIDS scourge throughout the world. The social vaccine suggested in this study can also be extended to all the high risk group population for successful prevention of this dreadful disease in the world.
Huang, Yunda; Karuna, Shelly T; Janes, Holly; Frahm, Nicole; Nason, Martha; Edlefsen, Paul T; Kublin, James G; Corey, Lawrence; McElrath, M Juliana; Gilbert, Peter B
Phase 1 preventive HIV vaccine trials are often designed as randomized, double-blind studies with the inclusion of placebo recipients. Careful consideration is needed to determine when the inclusion of placebo recipients is highly advantageous and when it is optional for achieving the study objectives of assessing vaccine safety, tolerability and immunogenicity. The inclusion of placebo recipients is generally important to form a reference group that ensures fair evaluation and interpretation of subjective study endpoints, or endpoints whose levels may change due to exposures besides vaccination. In some settings, however, placebo recipients are less important because other data sources and tools are available to achieve the study objectives.
Andrasik, Michele Peake; Yoon, Ro; Mooney, Jessica; Broder, Gail; Bolton, Marcus; Votto, Teress; Davis-Vogel, Annet
Observed seroincidence and prevalence rates in male-to-female (MTF) transgender individuals highlight the need for effective targeted HIV prevention strategies for this community. In order to develop an effective vaccine that can be used by transgender women, researchers must understand and address existing structural issues that present barriers to this group's participation in HIV vaccine clinical trials. Overcoming barriers to participation is important for ensuring HIV vaccine acceptability and efficacy for the MTF transgender community. To explore barriers and facilitators to MTF transgender participation in preventive HIV vaccine clinical trials, the HIV Vaccine Trials Network conducted focus groups among transgender women in four urban areas (Atlanta, Boston, Philadelphia, and San Francisco). Barriers and facilitators to engagement of transgender women in preventive HIV vaccine clinical trials led to the following recommendations: (a) transgender cultural competency training, (b) creating trans-friendly environments, (c) true partnerships with local trans-friendly organizations and health care providers, (d) protocols that focus on transgender specific issues, and (e) data collection and tracking of transgender individuals. These results have implications for the conduct of HIV vaccine trials, as well as engagement of transgender women in research programs in general.
Yoon, Ro; Mooney, Jessica; Broder, Gail; Bolton, Marcus; Votto, Teress; Davis-Vogel, Annet
Observed seroincidence and prevalence rates in male to female (MTF) transgender individuals highlight the need for effective targeted HIV prevention strategies for this community. In order to develop an effective vaccine that can be used by transgender women, researchers must understand and address existing structural issues that present barriers to this group’s participation in HIV vaccine clinical trials. Overcoming barriers to participation is important for ensuring HIV vaccine acceptability and efficacy for the MTF transgender community. To explore barriers and facilitators to MTF transgender participation in preventive HIV vaccine clinical trials, the HIV Vaccine Trials Network (HVTN) conducted focus groups among transgender women in four urban areas (Atlanta, Boston, Philadelphia and San Francisco). Barriers and facilitators to engagement of transgender women in preventive HIV vaccine clinical trials led to the following recommendations: (1) transgender cultural competency training; (2) creating trans-friendly environments; (3) true partnerships with local trans-friendly organizations and health care providers; (4) protocols that focus on transgender specific issues; and (5) data collection and tracking of transgender individuals. These results have implications for the conduct of HIV vaccine trials, as well as engagement of transgender women in research programs in general. PMID:23446435
Janes, Holly; Gilbert, Peter; Buchbinder, Susan; Kublin, James; Sobieszczyk, Magdalena E; Hammer, Scott M
The HIV prevention landscape is evolving rapidly, and future efficacy trials of candidate vaccines, which remain the best long-term option for stemming the HIV epidemic, will be conducted in the context of partially effective nonvaccine prevention modalities. It is essential that these trials provide for valid and efficient evaluation of vaccine efficacy and immune correlates. The availability of partially effective prevention modalities presents opportunities to study their interactions with vaccines to maximally reduce HIV incidence. This article proposes an approach for conducting future vaccine efficacy trials in the context of background use of partially effective nonvaccine prevention modalities, and for conducting future vaccine efficacy trials that provide nonvaccine prevention modalities in one or more of the randomized study groups. Strategies are discussed for responding to emerging evidence on nonvaccine prevention modalities during ongoing vaccine trials. Next-generation HIV vaccine efficacy trials will almost certainly be more complex in their design and implementation but may become more relevant to at-risk populations and better suited to the ultimate goal of reducing HIV incidence at the population level.
Wallace, Mark R.
Abstract Vaccines are critical components for protecting HIV-infected adults from an increasing number of preventable diseases. However, missed opportunities for vaccination among HIV-infected persons persist, likely due to concerns regarding the safety and efficacy of vaccines, as well as the changing nature of vaccine guidelines. In addition, the optimal timing of vaccination among HIV-infected adults in regards to HIV stage and receipt of antiretroviral therapy remain important questions. This article provides a review of the current recommendations regarding vaccines among HIV-infected adults and a comprehensive summary of the evidence-based literature of the benefits and risks of vaccines among this vulnerable population. PMID:25029589
Barouch, Dan H; Klasse, Per Johan; Dufour, Jason; Veazey, Ronald S; Moore, John P
Vaccination and the application of a vaginal microbicide have traditionally been considered independent methods to prevent the sexual transmission of HIV-1 to women. Both techniques can be effective in macaque models, and limited efficacy has been observed in clinical trials for each. Here, we have addressed whether vaccines and microbicides can be used together to provide reinforced protection against virus challenge of rhesus macaques. In two separate experiments, four groups of animals were vaccinated with a T-cell-based adenovirus (Ad) vectored vaccine aimed at reducing postinfection viral loads and/or a partially effective dose of a vaginal microbicide aimed at blocking infection of a high-dose vaginal challenge with SIVmac251 or SHIV-162P3. In the first study, the only two protected animals were in the group that received Ad26/Ad5HVR48 vaccine vectors combined with the fusion inhibitor T-1249 as the vaginal microbicide before SIVmac251 challenge. In the second study, vaccination with Ad35/Ad26 vectors combined with the CCR5 inhibitor maraviroc as the vaginal microbicide led to significant reductions of both acquisition of infection and postinfection viral loads following SHIV-SF162P3 challenge. As expected, the vaccine by itself reduced viral loads but had no acquisition effect, whereas the microbicide had a partial acquisition effect but minimal impact on viral loads. For both measures of protective efficacy, the vaccine-microbicide combination differed more from controls than did either separate intervention. Overall, the data suggest that vaccines and microbicides are complementary techniques that may protect better when used together than separately.
Webster, Diane E; Thomas, Merlin C; Pickering, Raelene; Whyte, Andrew; Dry, Ian B; Gorry, Paul R; Wesselingh, Steve L
Although educational programs have had some impact, immunization against HIV will be necessary to control the AIDS pandemic. To be effective, vaccination will need to be accessible and affordable, directed against multiple antigens, and delivered in multiple doses. Plant-based vaccines that are heat-stable and easy to produce and administer are suited to this type of strategy. Pilot studies by a number of groups have demonstrated that plant viral expression systems can produce HIV antigens in quantities that are appropriate for use in vaccines. In addition, these plant-made HIV antigens have been shown to be immunogenic. However, given the need for potent cross-clade humoral and T-cell immunity for protection against HIV, and the uncertainty surrounding the efficacy of protein subunit vaccines, it is most likely that plant-made HIV vaccines will find their niche as booster immunizations in prime-boost vaccination schedules.
Albright, Kendra S.; Gavigan, Karen
HIV/AIDS infections are growing at an alarming rate for young adults. In 2009, youth, ages 13-29, accounted for 39% of all new HIV infections in the U.S. (Division of HIV/ AIDS Prevention, Centers for Disease Control (CDC), 2011). South Carolina ranks eighth in the nation for new HIV cases, while the capital city of Columbia ranks seventh…
This study analyses the priorities of public donors in funding HIV prevention by either integrated condom programming or HIV preventive microbicides and vaccines in the period between 2000 and 2008. It further compares the public funding investments of the USA government and European governments, including the EU, as we expect the two groups to invest differently in HIV prevention options, because their policies on sexual and reproductive health and rights are different. We use two existing officially UN endorsed databases to compare the public donor funding streams for HIV prevention of these two distinct contributors. In the period 2000-2008, the relative share of public funding for integrated condom programming dropped significantly, while that for research on vaccines and microbicides increased. The European public donors gave a larger share to condom programming than the United States, but exhibited a similar downward trend in favour of funding research on vaccines and microbicides. Both public donor parties invested progressively more in research on vaccines and microbicides rather than addressing the shortage of condoms and improving access to integrated condom programming in developing countries. PMID:21192787
... Services HIV Overview What is a Therapeutic HIV Vaccine? (Last updated 10/17/2016; last reviewed 10/ ... from the body. What is a therapeutic HIV vaccine? A therapeutic HIV vaccine is a vaccine that’s ...
Fuchs, Jonathan D.; Sobieszczyk, Magdalena E.; Madenwald, Tamra; Grove, Doug; Karuna, Shelly T.; Andrasik, Michele; Sherwat, Adam; Broder, Gail; Mayer, Kenneth; Koblin, Beryl; Hammer, Scott
In November 2010, the iPrEx study reported that pre-exposure prophylaxis (PrEP) with daily tenofovir disoproxil fumarate/emtricitabine reduced HIV infections by 44% among men who have sex with men and subsequent trials corroborated efficacy among heterosexual men and women. During regularly scheduled follow-up visits from January-March 2011, participants in an ongoing phase 2b vaccine efficacy trial completed an anonymous web survey about PrEP. Among 376 respondents, 17% reported they were very likely to use PrEP in the next year. Non-white participants were more likely to use PrEP. Among those with some level of interest, intent to use PrEP was greatest if the drug were available through the clinical trial or health insurance. Most (91%) believed taking PrEP would not change their willingness to stay in the vaccine trial and few thought it would affect recruitment. As key stakeholders, currently enrolled trial participants can offer vital input about emerging prevention technologies that may affect the design of future HIV vaccine and non-vaccine prevention trials. PMID:23614998
Rafferty, Hannah; Sibeko, Sengeziwe; Rowland-Jones, Sarah
The human immunodeficiency virus (HIV) burden in women continues to increase, and heterosexual contact is now the most common route of infection worldwide. Effective protection of women against HIV-1 infection may require a vaccine specifically targeting mucosal immune responses in the female genital tract (FGT). To achieve this goal, a much better understanding of the immunology of the FGT is needed. Here we review the architecture of the immune system of the FGT, recent studies of potential methods to achieve the goal of mucosal protection in women, including systemic-prime, mucosal-boost, FGT-tropic vectors and immune response altering adjuvants. Advances in other fields that enhance our understanding of female genital immune correlates and the interplay between hormonal and immunological systems may also help to achieve protection of women from HIV infection. PMID:25408686
Fuchs, Jonathan D; Sobieszczyk, Magdalena E; Madenwald, Tamra; Grove, Doug; Karuna, Shelly T; Andrasik, Michele; Sherwat, Adam; Broder, Gail; Mayer, Kenneth; Koblin, Beryl; Hammer, Scott
In November 2010, the iPrEx study reported that preexposure prophylaxis (PrEP) with daily tenofovir disoproxil fumarate/emtricitabine reduced HIV infections by 44% among men who have sex with men and subsequent trials corroborated efficacy among heterosexual men and women. During regularly scheduled follow-up visits from January to March 2011, participants in an ongoing phase 2b vaccine efficacy trial completed an anonymous Web survey about PrEP. Among 376 respondents, 17% reported they were very likely to use PrEP in the next year. Nonwhite participants were more likely to use PrEP. Among those with some level of interest, intent to use PrEP was greatest if the drug were available through the clinical trial or health insurance. Most (91%) believed taking PrEP would not change their willingness to stay in the vaccine trial and few thought it would affect recruitment. As key stakeholders, currently enrolled trial participants can offer vital input about emerging prevention technologies that may affect the design of future HIV vaccine and nonvaccine prevention trials.
Etcheverry, M. Florencia; Evans, Jennifer L.; Sanchez, Emilia; Mendez-Arancibia, Eva; Meroño, Mercé; Gatell, José M.; Page, Kimberly; Joseph, Joan
The potential for implementation of HIV vaccine trials in hard-to-reach female sex workers in an inner city area of Barcelona, Spain was assessed via a study of HIV risk, willingness to participate and the success of retention strategies. In 130 women, serological HIV status, behavioral risk exposures and willingness to participate in future HIV vaccine trials were recorded every six months using a confidential questionnaire. An enhanced retention (ER) strategy was compared with a control retention (CR) strategy comprising the recording of data on appointment cards. HIV seroincidence and retention rates were estimated. Retention rates after 6 and 12 mo of follow-up in the ER group were 76% and 69% respectively compared with 16% and 13% in the CR group. Among the ER group 97% were willing to participate in HIV vaccine trials at baseline and, after 12 mo of follow-up. Willingness was significantly associated with higher HIV risk exposure, and higher education level. Successfully retaining these cohorts over time in settings with a high HIV seroincidence rate is an ongoing challenge that will need to be addressed to ensure participation in future trials. Furthermore, as we have demonstrated, the fact that retaining hard-to-reach populations is difficult should not exclude this target population for HIV vaccine and prevention trials. PMID:23291931
... medicines to treat HIV (called antiretroviral therapy, or ART) the right way, every day. They can keep ... to treat HIV infection (called antiretroviral therapy, or ART) the right way, every day and his or ...
The best long-term hope for controlling the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) pandemic is a safe, effective and affordable preventive vaccine, but its development has encountered unprecedented scientific challenges. The first phase I trial of an HIV vaccine was conducted in 1987. Subsequently, more than 30 candidate vaccines have been tested in over 60 phase I/II trials, involving approximately 10 000 healthy volunteers. Most of these trials have been conducted in the USA and Europe, but several have also been conducted in developing countries. The first phase III trials began in the USA in 1998 and in Thailand in 1999 to assess the efficacy of the first generation of HIV vaccines (based on the HIV envelope protein, gp120); the results will be available within the next 1-2 years. To accelerate the development of an HIV vaccine, additional candidate vaccines must be evaluated in parallel in both industrialized and developing countries. This will require international collaboration and coordination and critical ethical issues will need to be addressed. To ensure that future HIV vaccines contribute to the overall HIV/AIDS prevention effort, we should begin planning now on how best to use them. PMID:11799445
Sayles, Jennifer N.; Macphail, Catherine L.; Newman, Peter A.; Cunningham, William E.
Developing and disseminating a preventive HIV vaccine is a primary scientific and public health objective. However, little is known about HIV vaccine acceptability in the high prevalence setting of South Africa—where young adults are likely to be targeted in early dissemination efforts. In 2007, we conducted six focus groups (n=42) with South Africans aged 18-24 years old. We used a deductive framework approach to identify key motivators and barriers to future HIV vaccine uptake. Participants identified HIV testing, HIV stigma, mistrust of the health care system, and concerns about sexual disinhibition as barriers to vaccine uptake. For women, family members and friends were strong motivators for vaccine uptake, while men were more likely to see vaccines as an opportunity to stop using HIV prevention strategies such as condoms and partner reductions. Implications of these findings for developing HIV vaccine dissemination strategies and policy in South Africa are discussed. PMID:19509123
Day, Tracey A.; Kublin, James G.
The past few years have witnessed many promising advances in HIV prevention strategies involving pre-exposure prophylaxis approaches. Some may now wonder whether an HIV vaccine is still needed, and whether developing one is even possible. The partial efficacy reported in the RV144 trial and the encouraging results of the accompanying immune correlates analysis suggest that an effective HIV vaccine is achievable. These successes have provided a large impetus and guidance for conducting more HIV vaccine trials. A key lesson learned from RV144 is that assessment of HIV acquisition is now a feasible and valuable primary objective for HIV preventive vaccine trials. In this article we review how RV144 and other HIV vaccine efficacy trials have instructed the field and highlight some of the HIV vaccine concepts in clinical development. After a long and significant investment, HIV vaccine clinical research is paying off in the form of valuable lessons that, if applied effectively, will accelerate the path toward a safe and effective vaccine. Together with other HIV prevention approaches, preventive and therapeutic HIV vaccines will be invaluable tools in bringing the epidemic to an end. PMID:24033299
Vanniasinkam, T; Ertl, H C J
The AIDS epidemic continues to spread throughout nations of Africa and Asia and is by now threatening to undermine the already frail infrastructure of developing countries in Sub-Saharan Africa that are hit the hardest. The only option to stem this epidemic is through inexpensive and efficacious vaccines that prevent or at least blunt HIV-1 infections. Despite decades of pre-clinical and clinical research such vaccines remain elusive. Most anti-viral vaccines act by inducing protective levels of virus-neutralizing antibodies. The envelope protein of HIV-1, the sole target of neutralizing antibodies, is constantly changing due to mutations, B cell epitopes are masked by heavy glycosylation and the protein's structural unfolding upon binding to its CD4 receptor and chemokine co-receptors. Efforts to induce broadly cross-reactive virus-neutralizing antibodies able to induce sterilizing or near sterilizing immunity to HIV-1 have thus failed. Studies have indicated that cell-mediated immune responses and in particular CD8+ T cell responses to internal viral proteins may control HIV-1 infections without necessarily preventing them. Adenoviral vectors expressing antigens of HIV-1 are eminently suited to stimulate potent CD8+ T cell responses against transgene products, such as antigens of HIV-1. They performed well in pre-clinical studies in rodents and nonhuman primates and are currently in human clinical trials. This review summarizes the published literature on adenoviral vectors as vaccine carriers for HIV-1 and discusses advantages and disadvantages of this vaccine modality.
Skinner, G R; Davies, J A; Sheasby, M; Mahmood, N
A candidate HIV subunit vaccine NFU.Ac.HIV[JM] was prepared by detergent and formaldehyde treatment of HIV-infected JM cells. The preparation contained HIV polypeptides at 200, 118, 70, 41 and 24 kD, with reactivity by immunoblotting of approximately fifteen virus-specific polypeptides including polypeptides at 119, 55, 41 and 24 kD, which may represent gp 120, p55, gp41 and p24, respectively. The content of gp120 was estimated to be 5 micrograms/ml. The vaccine was immunogenic in a rabbit, inducing neutralising antibody and reactivity by ELISA and by immunoblotting against a number of HIV polypeptides including those of molecular weights 24, 41, 55 nd 120 kD. The vaccine contained no infectious HIV or reverse transcriptase enzyme activity.
Lema, D; Garcia, A; De Sanctis, J B
The scope of the article is to review the different approaches that have been used for HIV vaccines. The review is based on articles retrieved by PubMed and clinical trials from 1990 up to date. The article discusses virus complexity, protective and non-protective immune responses against the virus, and the most important approaches for HIV vaccine development.
Summary Despite three decades of intensive research efforts, the development of an effective prophylactic vaccine against HIV remains an unrealized goal in the global campaign to contain the HIV/AIDS pandemic. Recent characterization of novel epitopes for inducing broadly neutralizing antibodies (BnAbs) has fueled research in the design and synthesis of new, well-defined antigenic constructs for the development of HIV envelope-directed vaccines. The present review will cover previous and recent efforts toward the design of synthetic vaccines based on the HIV viral envelope (Env) glycoproteins, with special emphasis on examples from our own laboratories. The biological evaluation of some of the most representative vaccine candidates, in terms of their antigenicity and immunogenicity, will also be discussed to illustrate the current state-of-the-art toward the development of fully synthetic HIV vaccines. PMID:25824661
Fernández-Tejada, Alberto; Haynes, Barton F; Danishefsky, Samuel J
Despite three decades of intensive research efforts, the development of an effective prophylactic vaccine against HIV remains an unrealized goal in the global campaign to contain the HIV/AIDS pandemic. Recent characterization of novel epitopes for inducing broadly neutralizing antibodies has fueled research in the design and synthesis of new, well-defined antigenic constructs for the development of HIV envelope-directed vaccines. The present review will cover previous and recent efforts toward the design of synthetic vaccines based on the HIV viral envelope glycoproteins, with special emphasis on examples from our own laboratories. The biological evaluation of some of the most representative vaccine candidates, in terms of their antigenicity and immunogenicity, will also be discussed to illustrate the current state-of-the-art toward the development of fully synthetic HIV vaccines.
Koff, Wayne C; Russell, Nina D; Walport, Mark; Feinberg, Mark B; Shiver, John W; Karim, Salim Abdool; Walker, Bruce D; McGlynn, Margaret G; Nweneka, Chidi Victor; Nabel, Gary J
Human immunodeficiency virus (HIV), the etiologic agent that causes AIDS, is the fourth largest killer in the world today. Despite the remarkable achievements in development of anti-retroviral therapies against HIV, and the recent advances in new prevention technologies, the rate of new HIV infections continue to outpace efforts on HIV prevention and control. Thus, the development of a safe and effective vaccine for prevention and control of AIDS remains a global public health priority and the greatest opportunity to eventually end the AIDS pandemic. Currently, there is a renaissance in HIV vaccine development, due in large part to the first demonstration of vaccine induced protection, albeit modest, in human efficacy trials, a generation of improved vaccine candidates advancing in the clinical pipeline, and newly defined targets on HIV for broadly neutralizing antibodies. The main barriers to HIV vaccine development include the global variability of HIV, lack of a validated animal model, lack of correlates of protective immunity, lack of natural protective immune responses against HIV, and the reservoir of infected cells conferred by integration of HIV's genome into the host. Some of these barriers are not unique to HIV, but generic to other variable viral pathogens such as hepatitis C and pandemic influenza. Recommendations to overcome these barriers are presented in this document, including but not limited to expansion of efforts to design immunogens capable of eliciting broadly neutralizing antibodies against HIV, expansion of clinical research capabilities to assess multiple immunogens concurrently with comprehensive immune monitoring, increased support for translational vaccine research, and engaging industry as full partners in vaccine discovery and development.
Moodley, Nishila; Gray, Glenda; Bertram, Melanie
Abstract Despite comprising 0.7% of the world population, South Africa is home to 18% of the global human immunodeficiency virus (HIV) prevalence. Unyielding HIV subepidemics among adolescents threaten national attempts to curtail the disease burden. Should an HIV vaccine become available, establishing its point of entry into the health system becomes a priority. This study assesses the impact of school-based HIV vaccination and explores how variations in vaccine characteristics affect cost-effectiveness. The cost per quality adjusted life year (QALY) gained associated with school-based adolescent HIV vaccination services was assessed using Markov modeling that simulated annual cycles based on national costing data. The estimation was based on a life expectancy of 70 years and employs the health care provider perspective. The simultaneous implementation of HIV vaccination services with current HIV management programs would be cost-effective, even at relatively higher vaccine cost. At base vaccine cost of US$ 12, the incremental cost effectiveness ratio (ICER) was US$ 43 per QALY gained, with improved ICER values yielded at lower vaccine costs. The ICER was sensitive to duration of vaccine mediated protection and variations in vaccine efficacy. Data from this work demonstrate that vaccines offering longer duration of protection and at lower cost would result in improved ICER values. School-based HIV vaccine services of adolescents, in addition to current HIV prevention and treatment health services delivered, would be cost-effective. PMID:26825890
Excler, Jean-Louis; Robb, Merlin L; Kim, Jerome H
The development of a safe and effective preventive HIV-1 vaccine remains a public health priority. Despite scientific difficulties and disappointing results, HIV-1 vaccine clinical development has, for the first time, established proof-of-concept efficacy against HIV-1 acquisition and identified vaccine-associated immune correlates of risk. The correlate of risk analysis showed that IgG antibodies against the gp120 V2 loop correlated with decreased risk of HIV infection, while Env-specific IgA directly correlated with increased risk. The development of vaccine strategies such as improved envelope proteins formulated with potent adjuvants and DNA and vectors expressing mosaics, or conserved sequences, capable of eliciting greater breadth and depth of potentially relevant immune responses including neutralizing and non-neutralizing antibodies, CD4+ and CD8+ cell-mediated immune responses, mucosal immune responses, and immunological memory, is now proceeding quickly. Additional human efficacy trials combined with other prevention modalities along with sustained funding and international collaboration remain key to bring an HIV-1 vaccine to licensure.
Chapman, Rosamund; Chege, Gerald; Shephard, Enid; Stutz, Helen; Williamson, Anna-Lise
HIV-1 has resulted in a devastating AIDS pandemic. An effective HIV/AIDS vaccine that can be used to either, prevent HIV infection, control infection or prevent progression of the disease to AIDS is needed. In this review we discuss the use of Mycobacterium bovis BCG, the tuberculosis vaccine, as a vaccine vector for an HIV vaccine. Numerous features make BCG an attractive vehicle to deliver HIV antigens. It has a good safety profile, elicits long-lasting cellular immune responses and in addition manufacturing costs are affordable, a necessary consideration for developing countries. In this review we discuss the numerous factors that influence generation of a genetically stable recombinant BCG vaccine for HIV. PMID:20353397
Sayles, Jennifer N.; Macphail, Catherine L.; Newman, Peter A.; Cunningham, William E.
Developing and disseminating a preventive HIV vaccine is a primary scientific and public health objective. However, little is known about HIV vaccine acceptability in the high-prevalence setting of South Africa--where young adults are likely to be targeted in early dissemination efforts. This study reports on six focus groups (n = 42) conducted in…
Vaccinations for Adults with HIV Infection The table below shows which vaccinations you should have to protect your health if ... sure you and your healthcare provider keep your vaccinations up to date. Vaccine Do you need it? ...
Liu, Jun; Ostrowski, Mario
A phase III clinical trial finished in Thailand recently showed that an ALVAC HIV-1 vaccine prime-gp120 protein boost vaccination regimen could modestly protect persons from HIV-1 infection, demonstrating that development of an effective and safe HIV-1 preventive vaccine is possible. ALVAC HIV-1 vaccines are candidate HIV-1 vaccines based on canarypox vectors. Previous clinical trials proved that ALVAC HIV-1 vaccines were safe but weak in immunogenicity when used in human subjects. We have been exploring to use tumor necrosis factor superfamily (TNFSF) members as adjuvants to enhance the immunogenicity of ALVAC HIV-1 vaccines. In this commentary, we will summarize our findings in using two TNFSF molecules, CD40L and OX40L, as adjuvants for an ALVAC HIV-1 vaccine in mouse model. We will also briefly discuss the challenges and prospects of using TNFSF molecules as adjuvants for HIV-1 vaccines in humans.
Pavot, Vincent; Rochereau, Nicolas; Lawrence, Philip; Girard, Marc P; Genin, Christian; Verrier, Bernard; Paul, Stéphane
In spite of several attempts over many years at developing a HIV vaccine based on classical strategies, none has convincingly succeeded to date. As HIV is transmitted primarily by the mucosal route, particularly through sexual intercourse, understanding antiviral immunity at mucosal sites is of major importance. An ideal vaccine should elicit HIV-specific antibodies and mucosal CD8⁺ cytotoxic T-lymphocyte (CTL) as a first line of defense at a very early stage of HIV infection, before the virus can disseminate into the secondary lymphoid organs in mucosal and systemic tissues. A primary focus of HIV preventive vaccine research is therefore the induction of protective immune responses in these crucial early stages of HIV infection. Numerous approaches are being studied in the field, including building upon the recent RV144 clinical trial. In this article, we will review current strategies and briefly discuss the use of adjuvants in designing HIV vaccines that induce mucosal immune responses.
Long, Elisa F; Brandeau, Margaret L; Owens, Douglas K
Estimating the potential health benefits and expenditures of a partially effective HIV vaccine is an important consideration in the debate about whether HIV vaccine research should continue. We developed an epidemic model to estimate HIV prevalence, new infections, and the cost-effectiveness of vaccination strategies in the U.S. Vaccines with modest efficacy could prevent 300,000-700,000 HIV infections and save $30 billion in healthcare expenditures over 20 years. Targeted vaccination of high-risk individuals is economically efficient, but difficulty in reaching these groups may mitigate these benefits. Universal vaccination is cost-effective for vaccines with 50% efficacy and price similar to other infectious disease vaccines.
Haynes, Barton F.
Development of a safe and effective vaccine for HIV is a major global priority. However, to date, efforts to design an HIV vaccine with methods used for development of other successful viral vaccines have not succeeded due to HIV diversity, HIV integration into the host genome, and ability of HIV to consistently evade anti-viral immune responses. Recent success in isolation of potent broadly neutralizing antibodies (bnAbs), discovery of mechanisms of bnAb induction, and in discovery of atypical mechanisms of CD8 T cell killing of HIV-infected cells, have opened new avenues for strategies for HIV vaccine design. PMID:26056742
Saunders, Kevin O; Rudicell, Rebecca S; Nabel, Gary J
There is renewed optimism that the goal of developing a highly effective AIDS vaccine is attainable. The HIV-1 vaccine field has seen its first trial of a vaccine candidate that prevents infection. Although modest in efficacy, this finding, along with the recent discovery that the human immune system can produce broadly neutralizing antibodies capable of inhibiting greater than 90% of circulating viruses, provides a guide for the rational design of vaccines and protection by passive immunization. Together, these findings will help shape the next generation of HIV vaccines.
Liu, Zuqiang; Xiao, Yi; Chen, Ying-Hua
Vaccines play important roles in preventing infectious diseases caused by different pathogens. However, some pathogens such as HIV-1 challenge current vaccine strategy. Poor immunogenicity and the high mutation rate of HIV-1 make great difficulties in inducing potent immune responses strong enough to prevent infection via vaccination. Epitope-vaccine, which could intensively enhance predefined epitope-specific immune responses, was suggested as a new strategy against HIV-1 and HIV-1 mutation. Epitope-vaccines afford powerful approaches to elicit potent, broad and complete immune protection against not only primary homologous viral isolates but also heterologous viral mutants. Although most studies are still preliminary now, epitope-vaccine as a novel strategy against the AIDS epidemic has great developmental potential. To trigger T-cell-dependent IgG antibody responses and improve affinities of the epitope-specific antibodies, approaches such as recombinant multi-epitope-vaccination and prime-boosting vaccination were suggested. Cellular immune responses, especially CTL responses, could also be elicited and enhanced in addition to humoral immune responses. Developed epitope-vaccines activating both arms of the immune system would benefit prevention and immunotherapy not only against HIV but also other chronic infections.
Kumar, Rajiv; Engwerda, Christian
Leishmaniasis is a parasitic disease that encompasses a range of clinical manifestations affecting people in tropical and subtropical regions of the world. Epidemiological and experimental data indicate that protection from disease can be achieved in most people. In addition, we know how the host immune system must respond to infection in order to control parasite growth. However, there is still no vaccine for use in humans. Here, we review our understanding of host immunity following Leishmania infection and also discuss recent advances in the development of vaccines to prevent leishmaniasis, highlighting a new promising approach that targets the parasite hemoglobin receptor. PMID:25505961
Novak, Richard M.; Metch, Barbara; Buchbinder, Susan; Cabello, Robinson; Donastorg, Yeycy; Figoroa, John-Peter; Adbul-Jauwad, Hend; Joseph, Patrice; Koenig, Ellen; Metzger, David; Sobieszycz, Magda; Tyndall, Mark; Zorilla, Carmen
Objectives Report of risk behavior, HIV incidence, and pregnancy rates among women participating in the Step Study, a phase IIB trial of MRKAd5 HIV-1 gag/pol/nef vaccine in HIV-negative individuals who were at high risk of HIV-1. Design Prospective multicenter, double-blinded, placebo-controlled trial Methods Women were from North American (NA) and Caribbean and South America (CSA) sites. Risk behavior was collected at screening and 6-month intervals. Differences in characteristics between groups were tested with Chi-square, two-sided Fisher’s exact tests, and Wilcoxon rank sum tests. Generalized estimating equation models were used to assess behavioral change. Results Among 1134 enrolled women, the median number of male partners was 18; 73.8% reported unprotected vaginal sex, 15.9% unprotected anal sex and 10.8% evidence of a sexually transmitted infection in the 6 months prior to baseline. With 3344 person-years (p–y) of follow up, there were 15 incident HIV infections: incidence rate was 0.45 per 100/p-y (95% CI 0.25, 0.74). Crack cocaine use in both regions (relative risk [RR]=2.4 [1.7,3.3]) and in CSA, unprotected anal sex (RR=6.4 [3.8. 10.7]) and drug use (RR=4.1 [2.1, 8.0]) were baseline risk behaviors associated with HIV acquisition. There was a marked reduction in risk behaviors after study enrollment with some recurrence in unprotected vaginal sex. Of 963 non-sterilized women, 304 (31.6%) became pregnant. Conclusions Crack cocaine use and unprotected anal sex are important risk criteria to identify high-risk women for HIV efficacy trials. Pregnancy during the trial was a common occurrence and needs to be considered in trial planning for prevention trials in women. PMID:23807272
Despite the tremendous efforts to develop a successful human immunodeficiency virus (HIV) vaccine, the quest for a safe and effective HIV vaccine seems to be remarkably long and winding. Disappointing results from previous clinical trials of VaxGen's AIDSVAXgp120 vaccine and MRKAd5 HIV-1 Gag/Pol/Nef vaccine emphasize that understanding the correlates of immune protection in HIV infection is the key to solve the puzzle. The modest vaccine efficacy from RV144 trial and the successive results obtained from the correlate of risk analysis have reinvigorated the HIV vaccine research field leading to various novel strategies. This paper will review the brief history and recent advances in HIV vaccine development. PMID:26866018
Clark, K; Cavicchi, J; Jensen, K; Fitzgerald, R; Bennett, A; Kowalski, S P
Global access to advanced vaccine technologies is challenged by the interrelated components of intellectual property (IP) management strategies, technology transfer (legal and technical) capabilities and the capacity necessary for accelerating R&D, commercialization and delivery of vaccines. Due to a negative association with the management of IP, patents are often overlooked as a vast resource of freely available, information akin to scientific journals as well as business and technological information and trends fundamental for formulating policies and IP management strategies. Therefore, a fundamental step towards facilitating global vaccine access will be the assembly, organization and analysis of patent landscapes, to identify the amount of patenting, ownership (assignees) and fields of technology covered. This is critical for making informed decisions (e.g., identifying licensees, building research and product development collaborations, and ascertaining freedom to operate). Such information is of particular interest to the HIV vaccine community where the HIV Vaccine Enterprise, have voiced concern that IP rights (particularly patents and trade secrets) may prevent data and materials sharing, delaying progress in research and development of a HIV vaccine. We have compiled and analyzed a representative HIV vaccine patent landscape for a prime-boost, DNA/adenoviral vaccine platform, as an example for identifying obstacles, maximizing opportunities and making informed IP management strategy decisions towards the development and deployment of an efficacious HIV vaccine.
Ross, Anna Laura; Bråve, Andreas; Scarlatti, Gabriella; Manrique, Amapola; Buonaguro, Luigi
The search for an HIV/AIDS vaccine is steadily moving ahead, generating and validating new concepts in terms of novel vectors for antigen delivery and presentation, new vaccine and adjuvant strategies, alternative approaches to design HIV-1 antigens for eliciting protective cross-neutralising antibodies, and identification of key mechanisms in HIV infection and modulation of the immune system. All these different perspectives are contributing to the unprecedented challenge of developing a protective HIV-1 vaccine. The high scientific value of this massive effort is its great impact on vaccinology as a whole, providing invaluable scientific information for the current and future development of new preventive vaccine as well as therapeutic knowledge-based infectious-disease and cancer vaccines.
Gallo, Robert C
Human immunodeficiency virus (HIV) genome integration indicates that persistent sterilizing immunity will be needed for a successful vaccine candidate. This suggests a need for broad antibodies targeting the Env protein. Immunogens targeting gp120 have been developed that block infection in monkeys and mimic the modest success of the RV144 clinical trial in that protection is short-lived following a decline in antibody-depending cell-mediated cytotoxicity-like antibodies. Attempts to induce antibody persistence have been complicated by a loss of efficacy, presumably by increasing the number of HIV-target cells. The key seems to be achieving an immune balance.
A Polyvalent Clade B Virus-Like Particle HIV Vaccine Combined with Partially Protective Oral Preexposure Prophylaxis Prevents Simian–Human Immunodeficiency Virus Infection in Macaques and Primes for Virus-Amplified Immunity
Ross, Ted M.; Pereira, Lara E.; Luckay, Amara; McNicholl, Janet M.; García-Lerma, J. Gerardo; Heneine, Walid; Eugene, Hermancia S.; Pierce-Paul, Brooke R.; Zhang, Jining; Hendry, R. Michael
Abstract Vaccination and preexposure prophylaxis (PrEP) with antiretrovirals have shown only partial protection from HIV-1 infection in human trials. Oral Truvada (emtricitabine/tenofovir disoproxil fumarate) is FDA approved as PrEP but partial adherence reduces efficacy. If combined as biomedical preventions (CBP), an HIV vaccine could protect when PrEP adherence is low and PrEP could prevent vaccine breakthroughs. The efficacy of combining oral PrEP with an HIV vaccine has not been evaluated in humans. We determined the efficacy of combining a DNA/virus-like particle (VLP) vaccine with partially effective intermittent PrEP in Indian rhesus macaques (RM). Eight RM received intramuscular inoculations of five DNA plasmids encoding four HIV-1 Clade B primary isolate Envs and SIVmac239 Gag (at weeks 0 and 4), followed by intramuscular and intranasal inoculations of homologous Gag VLPs and four Env VLPs (at weeks 12, 16, and 53). At week 61, we initiated weekly rectal exposures with heterologous SHIV162p3 (10 TCID50) along with oral Truvada (TDF, 22 mg/kg; FTC 20 mg/kg) dosing 2 h before and 22 h after each exposure. This PrEP regimen previously demonstrated 50% efficacy. Five controls (no vaccine, no PrEP) received weekly SHIV162p3. All controls were infected after a median of four exposures; the mean peak plasma viral load (VL) was 3.9×107 vRNA copies/ml. CBP protected seven of eight (87.5%) RM. The one infected CBP RM had a reduced peak VL of 8.8×105 copies/ml. SHIV exposures during PrEP amplified Gag and Env antibody titers in protected RM. These results suggest that combining oral PrEP with HIV vaccines could enhance protection against HIV-1 infection. PMID:24914761
Voronin, Yegor; Zinszner, Helene; Karg, Carissa; Brooks, Katie; Coombs, Robert; Hural, John; Holt, Renee; Fast, Pat; Allen, Mary; Allen, Mary; Busch, Michael; Fast, Pat; Fruth, Ulrich; Golding, Hana; Khurana, Surender; Mulenga, Joseph; Peel, Sheila; Schito, Marco; Voronin, Yegor; Barnabas, Nomampondo; Bentsen, Christopher; Graham, Barney; Gray, Glenda; Levin, Andrew; McCluskey, Margaret; O'Connell, Robert; Snow, Bill; Ware, Mark
Antibody-inducing vaccines are a major focus in the preventive HIV vaccine field. Because the most common tests for HIV infection rely on detecting antibodies to HIV, they may also detect antibodies induced by a candidate HIV vaccine. The detection of vaccine-induced antibodies to HIV by serological tests is most commonly referred to as vaccine-induced sero-reactivity (VISR). VISR can be misinterpreted as a sign of HIV infection in a healthy study participant. In a participant who has developed vaccine-induced antibodies, accurate diagnosis of HIV infection (or lack thereof) may require specialized tests and algorithms (differential testing) that are usually not available in community settings. Organizations sponsoring clinical testing of preventive HIV vaccine candidates have an ethical obligation not only to inform healthy volunteers about the potential problems associated with participating in a clinical trial but also to help manage any resulting issues. This article explores the scope of VISR-related issues that become increasingly prevalent as the search for an effective HIV vaccine continues and will be paramount once a preventive vaccine is deployed. We also describe ways in which organizations conducting HIV vaccine trials have addressed these issues and outline areas where more work is needed. PMID:25649349
Corey, Lawrence; Nabel, Gary J; Dieffenbach, Carl; Gilbert, Peter; Haynes, Barton F; Johnston, Margaret; Kublin, James; Lane, H Clifford; Pantaleo, Giuseppe; Picker, Louis J; Fauci, Anthony S
Developing a vaccine against the human immunodeficiency virus (HIV) poses an exceptional challenge. There are no documented cases of immune-mediated clearance of HIV from an infected individual, and no known correlates of immune protection. Although nonhuman primate models of lentivirus infection have provided valuable data about HIV pathogenesis, such models do not predict HIV vaccine efficacy in humans. The combined lack of a predictive animal model and undefined biomarkers of immune protection against HIV necessitate that vaccines to this pathogen be tested directly in clinical trials. Adaptive clinical trial designs can accelerate vaccine development by rapidly screening out poor vaccines while extending the evaluation of efficacious ones, improving the characterization of promising vaccine candidates and the identification of correlates of immune protection.
Kegeles, Susan M.; Johnson, Mallory O.; Strauss, Ronald P.; Ralston, Brady; Hays, Robert B.; Metzger, David S.; McLellan-Lemal, Eleanor; MacQueen, Kathleen M.
Developing an effective vaccine remains a critical long-term approach to HIV prevention. Every efficacy trial should be responsive to the concerns of participating communities because the successful development of an HIV preventive vaccine will require long-term involvement of people who have been marginalized and who distrust the government and…
Verma, Ramesh; Khanna, Pardeep; Chawla, Suraj; Dhankar, Mukesh
HIV infection is a major public health problem especially in the developing countries. Once a person infects with HIV, it remained infected for lifelong. The advanced stage developed after 10–15 y of HIV infection that stage is called acquired immunodeficiency syndrome (AIDS). From 1990 to 2000 the number of people living with HIV rose from 8 million to 27 million; since the beginning of the HIV/AIDS epidemic, AIDS has claimed almost 39million lives so far. Till now, there is no cure for HIV infection; however, after the introduction of effective treatment with antiretroviral (ARV) drugs the HIV individual can enjoy healthy and productive lives. Vaccine is safe and cost-effective to prevent illness, impairment, disability and death. Like other vaccines, a preventive HIV vaccine could help save millions of lives. All vaccines work the same way i.e. the antigen stimulate the immune system and develop antibodies. The ultimate goal is to develop a safe and effective vaccine that protects people worldwide from getting infected with HIV. However, some school of thought that vaccine may protects only some HIV people, it could have a major impact on the rates of transmission of HIV and this will help in control of epidemic, especially in populations where high rate of HIV transmission. In the past, some scientist doubted on the development of an effective polio vaccine, but now we are near to eradicate the polio from the world this is possible because of successful vaccination programmes. HIV vaccine research is aided by the not-for-profit International AIDS/HIV vaccine Initiative (IAVI), which helps to support and coordinate vaccine research, development, policy and advocacy around the world. Although the challenges for scientist are intimidating but scientists remain hopeful that they can develop safe and effective HIV vaccines for patients in future. PMID:26212081
Moodley, Nishila; Gray, Glenda; Bertram, Melanie
Despite comprising 0.7% of the world population, South Africa is home to 18% of the global human immunodeficiency virus (HIV) prevalence. Unyielding HIV subepidemics among adolescents threaten national attempts to curtail the disease burden. Should an HIV vaccine become available, establishing its point of entry into the health system becomes a priority. This study assesses the impact of school-based HIV vaccination and explores how variations in vaccine characteristics affect cost-effectiveness. The cost per quality adjusted life year (QALY) gained associated with school-based adolescent HIV vaccination services was assessed using Markov modeling that simulated annual cycles based on national costing data. The estimation was based on a life expectancy of 70 years and employs the health care provider perspective. The simultaneous implementation of HIV vaccination services with current HIV management programs would be cost-effective, even at relatively higher vaccine cost. At base vaccine cost of US$ 12, the incremental cost effectiveness ratio (ICER) was US$ 43 per QALY gained, with improved ICER values yielded at lower vaccine costs. The ICER was sensitive to duration of vaccine mediated protection and variations in vaccine efficacy. Data from this work demonstrate that vaccines offering longer duration of protection and at lower cost would result in improved ICER values. School-based HIV vaccine services of adolescents, in addition to current HIV prevention and treatment health services delivered, would be cost-effective.
Tanner, Helen; Dalgleish, Angus
Since the human immunodeficiency virus (HIV-1) pandemic began, few prophylactic vaccines have reached phase III trials. Only one has shown partial efficacy in preventing HIV-1 infection. The introduction of antiretroviral therapy (ART) has had considerable success in controlling infection and reducing transmission but in so doing has changed the nature of HIV-1 infection for those with access to ART. Access, compliance, and toxicity alongside the emergence of serious non-AIDS morbidity and the sometimes poor immune reconstitution in ART-treated patients have emphasized the need for additional therapies. Such therapy is intended to contribute to control of HIV-1 infection, permit structured treatment interruptions, or even establish a functional cure of permanently suppressed and controlled infection. Both immunotherapy and therapeutic vaccination have the potential to reach these goals. In this review, the latest developments in immunotherapy and therapeutic vaccination are discussed. PMID:24991420
... conjugate vaccine series which protects against meningococcal disease Hepatitis B vaccine series to protect against hepatitis B HPV vaccine ... conjugate vaccine series which protects against meningococcal disease Hepatitis B vaccine series to protect against hepatitis B HPV vaccine ...
Van Der Ryst, E
According to animal studies, DNA vaccines employ the genes encoding proteins of pathogens or tumors, in contrast to the more conventional vaccine approaches. In addition, DNA vaccinations do not involve infectious agents, proteins are expressed in their natural form resulting to better recognition of viral proteins by the antibodies, and both strong and durable cellular immune responses as well as neutralizing antibodies are induced. Altogether, this makes DNA vaccinations one of the most promising future candidates in the field of HIV vaccines. However, safety of DNA vaccines should be examined before these vaccines can be considered for large-scale clinical trials in humans. The question of a possible induction of anti-DNA antibodies, with the consequent development of autoimmune manifestations is emphasized. Another is the possible integration of DNA with insertional mutagenesis, which could lead to tumor formation and development of immunologic tolerance of antigen production persists.
Fonseca, Maria Goretti P.; Forsythe, Steven; Menezes, Alexandre; Vuthoori, Shilpa; Possas, Cristina; Veloso, Valdiléa; de Fátima Lucena, Francisca; Stover, John
Background The AIDS epidemic in Brazil remains concentrated in populations with high vulnerability to HIV infection, and the development of an HIV vaccine could make an important contribution to prevention. This study modeled the HIV epidemic and estimated the potential impact of an HIV vaccine on the number of new infections, deaths due to AIDS and the number of people receiving ARV treatment, under various scenarios. Methods and Findings The historical HIV prevalence was modeled using Spectrum and projections were made from 2010 to 2050 to study the impact of an HIV vaccine with 40% to 70% efficacy, and 80% coverage of adult population, specific groups such as MSM, IDU, commercial sex workers and their partners, and 15 year olds. The possibility of disinhibition after vaccination, neglecting medium- and high-risk groups, and a disease-modifying vaccine were also considered. The number of new infections and deaths were reduced by 73% and 30%, respectively, by 2050, when 80% of adult population aged 15–49 was vaccinated with a 40% efficacy vaccine. Vaccinating medium- and high-risk groups reduced new infections by 52% and deaths by 21%. A vaccine with 70% efficacy produced a great decline in new infections and deaths. Neglecting medium- and high-risk population groups as well as disinhibition of vaccinated population reduced the impact or even increased the number of new infections. Disease-modifying vaccine also contributed to reducing AIDS deaths, the need for ART and new HIV infections. Conclusions Even in a country with a concentrated epidemic and high levels of ARV coverage, such as Brazil, moderate efficacy vaccines as part of a comprehensive package of treatment and prevention could have a major impact on preventing new HIV infections and AIDS deaths, as well as reducing the number of people on ARV. Targeted vaccination strategies may be highly effective and cost-beneficial. PMID:20668523
Kerwat, Klaus; Goedecke, Marcel; Wulf, Hinnerk
Vaccinations are among the most efficient and important preventive medical procedures. Modern vaccines are well tolerated. In Germany there are no longer laws for mandatory vaccinations, either for the general public or for medical personnel. Vaccinations are now merely "officially recommended" by the top health authorities on the basis of recommendations from the Standing Committee on Vaccinations (STIKO) of the Robert Koch Institute (RKI) according to § 20 para 3 of the Protection against Infection law (IfSG). The management of vaccine damage due to officially recommended vaccinations is guaranteed by the Federal States. Whereas vaccinations in childhood are generally considered to be a matter of course, the willingness to accept them decreases markedly with increasing age. In the medical sector vaccinations against, for example, hepatitis B are well accepted while other vaccinations against, for example, whooping cough or influenza are not considered to be so important. The fact that vaccinations, besides offering protection for the medical personnel, may also serve to protect the patients entrusted to medical care from nosocomial infections is often ignored.
Shapiro, Stuart Z
Realization of individual and public health benefit from an HIV vaccine requires clinical testing to demonstrate efficacy. To facilitate clinical testing, preclinical HIV vaccine developers should consider the realities of clinical practice and the conduct of clinical trials in product design. There are several essentially different approaches to prophylactic HIV vaccine design: (1) induce immunity that allows infection but reduces initial peak viremia and viral load set point; (2) induce immunity that allows infection but controls viremia to below the level of detection; (3) induce immunity that allows infection but promotes viral clearance before disease (classic vaccine approach); (4) induce "sterilizing immunity" that prevents acquisition of infection. Each approach presents different challenges for clinical product development. Current clinical trial practices and evolving treatment standards may make it infeasible to perform an efficacy trial of a preventive vaccine that only modestly reduces viremia. A vaccine that promotes control of viremia to below the level of detection is testable but will require extended follow-up to determine how long virus control persists; once control is lost boosting with the same vaccine may not be useful. A vaccine that permits infection but promotes subsequent complete clearance of the virus from the body will require the development and validation of an effective assay for virus clearance. A vaccine that prevents acquisition of infection is the most straightforward to test in the clinic, but escalating costs require more attention by vaccine developers to understanding how the vaccine works and the breadth of protection. All types of vaccine require attention to effect size to ensure adequate powering of efficacy trials.
Soon after HIV was discovered as the cause of AIDS in 1983–1984, there was an expectation that a preventive vaccine would be rapidly developed. The first HIV vaccine paradigm was aimed at inducing neutralizing antibodies, with numerous recombinant envelope proteins tested in clinical trials. It came to an end in 2003, with the negative results from the VaxGen trials in North America and Thailand. The second paradigm aimed at inducing CD8+ T-cell responses, and it led to the development of DNA vaccines and of live-recombinant viral vectors, especially poxviruses and adenoviruses (Ad). The concept was tested in the STEP and Phambili trials, using an Ad5 vector. The trials were stopped in 2007, after an interim review of STEP showed that the vaccine failed to prevent HIV infection or to decrease virus load in vaccinated volunteers who became infected, and even enhanced HIV acquisition in a subpopulation of vaccinated individuals. The current wave of vaccine development is attempting to induce more complex immune responses and exploring novel approaches. The RV 144 trial in Thailand, which assessed the protective efficacy of a prime-boost protocol using a canarypox vectors followed by gp120 boosts, showed 31.2% efficacy in preventing HIV acquisition and presumptive immune correlates have been identified. The field is now exploring new leads that include the rational design of novel immunogens based on epitopes recognized by broadly neutralizing antibodies, live replication-competent vectors and the role of potentially protective non-neutralizing antibodies.
Liu, Huan; Bi, Wenwen; Wang, Qian; Lu, Lu; Jiang, Shibo
This paper analyzes the main trend of the development of acquired immunodeficiency syndrome (AIDS) vaccines in recent years. Designing an HIV-1 vaccine that provides robust protection from HIV-1 infection remains a challenge despite many years of effort. Therefore, we describe the receptor binding domain of gp120 as a target for developing AIDS vaccines. And we recommend some measures that could induce efficiently and produce cross-reactive neutralizing antibodies with high binding affinity. Those measures may offer a new way of the research and development of the potent and broad AIDS vaccines.
Screening for the community-based, phase III, prime-boost HIV vaccine trial conducted in Thailand (also referred to as "RV144") began in September 2003 and concluded in December 2005 in Rayong and Chon Buri provinces. During this period 26,676 persons were consented and screened for vaccine trial eligibility in a separate protocol ("RV148") at 47 screening sites, of which 26,548 were tested for HIV, and 16,402 were ultimately enrolled in RV144 and received at least one vaccination or corresponding placebo injection. Fifty-eight percent of those enrolled in RV148 were men and roughly half of the men and women were married. A slight majority was born in the provinces in which the study was conducted. The median age was 23 (IQR 20-26) and most had achieved a level of education that was higher than grade 9, which is compulsory for Thai citizens. The prevalence of confirmed HIV infection was 1.6%; among persons who did not return for confirmatory testing, it was 2.0%. Eighty-three percent were infected with CRF01_AE strains (formerly subtype E) as determined by serological typing. The estimated incidence of HIV infection using a capture EIA assay was 0.19 per 100 person-years. Female sex, older age, single marital status, and lower educational attainment were associated with HIV infection. Persons who reported working in the fishing or sex-work industries were more frequently infected (2.4% and 4.1%, respectively), but accounted for a small percent of the tested population in RV148 (0.7% and 0.6%, respectively), reflecting the overall low-risk of HIV in this study. Those screened for eligibility but did not participate in the vaccine trial were not substantially different from enrolled vaccine trial subjects.
Lakhashe, Samir K; Silvestri, Guido; Ruprecht, Ruth M
Development of a safe and effective prophylactic HIV-1 vaccine presents unique challenges. The pessimism following the failure of two HIV-1 vaccine concepts in clinical trials, HIV-1 gp120 and an adenovirus-based approach to induce only cellular immune responses, has been replaced by cautious optimism engendered by the RV144 trial outcome, the isolation of several new broadly reactive neutralizing monoclonal antibodies, and recent primate model data indicating prevention of viral acquisition by active or passive immunization. Intense efforts are underway to optimize immunogen design, adjuvants, and the tools for preclinical evaluation of candidate vaccines in primates, where correlates of protection can be examined in detail - as proof-of-concept for clinical trials.
Safrit, Jeffrey T; Fast, Patricia E; Gieber, Lisa; Kuipers, Hester; Dean, Hansi J; Koff, Wayne C
Human immunodeficiency virus (HIV) is the cause of one of the most lethal pandemics in human history, although in recent years access to highly effective anti-retroviral therapy has provided new hope worldwide. Transmission of HIV by sexual contact, childbirth and injection drug use has been reduced, but 2 million are newly infected each year, and much of the transmission is from people who do not know their status. In addition to known methods, a preventive vaccine is needed to end the pandemic. The extraordinary mutability and genetic diversity of HIV is an enormous challenge, but vaccines are being designed for broad coverage. Computer-aided design of mosaic immunogens, incorporating many epitopes from the entire genome or from conserved regions aim to induce CD8+ T cells to kill virus-infected cells or inhibit virus replication, while trimeric envelope proteins or synthetic mimics aim to induce broadly reactive neutralizing antibodies similar to those cloned from some infected patients. Induction of more potent and durable responses may require new adjuvants or replicating chimeric vectors chimeras that bear HIV genes. Passive or genetic delivery of broadly neutralizing antibodies may provide broad protection and/or lead to insights for vaccine designers. Proof-of-concept trials in non-human primates and in one human efficacy trial have provided scientific clues for a vaccine that could provide broad and durable protection against HIV. The use of vaccines to destroy HIV reservoirs as part of therapy or cure is now also being explored.
Burton, Dennis R.; Ahmed, Rafi; Barouch, Dan H.; Butera, Salvatore T.; Crotty, Shane; Godzik, Adam; Kaufmann, Daniel E.; McElrath, M. Juliana; Nussenzweig, Michel C.; Pulendran, Bali; Scanlan, Chris N.; Schief, William R.; Silvestri, Guido; Streeck, Hendrik; Walker, Bruce D.; Walker, Laura M.; Ward, Andrew B.; Wilson, Ian A.; Wyatt, Richard
Despite numerous attempts over many years to develop an HIV vaccine based on classical strategies, none has convincingly succeeded to date. A number of approaches are being pursued in the field, including building upon possible efficacy indicated by the recent RV144 clinical trial, which combined two HIV vaccines. Here, we argue for an approach based, in part, on understanding the HIV envelope spike and its interaction with broadly neutralizing antibodies (bnAbs) at the molecular level and using this understanding to design immunogens as possible vaccines. BnAbs can protect against virus challenge in animal models and many such antibodies have been isolated recently. We further propose that studies focused on how best to provide T cell help to B cells that produce bnAbs are crucial for optimal immunization strategies. The synthesis of rational immunogen design and immunization strategies, together with iterative improvements, offers great promise for advancing toward an HIV vaccine. PMID:23084910
Dimitrov, Dobromir; Kublin, James G; Ramsey, Scott; Corey, Lawrence
As HIV-1 envelope immune responses are critical to vaccine related protection, most candidate HIV vaccines entering efficacy trials are based upon a clade specific design. This need for clade specific vaccine prototypes markedly reduces the implementation of potentially effective HIV vaccines. We utilized a mathematical model to determine the effectiveness of immediate roll-out of a non-clade matched vaccine with reduced efficacy compared to constructing clade specific vaccines, which would take considerable time to manufacture and test in safety and efficacy trials. We simulated the HIV epidemic in San Francisco (SF) and South Africa (SA) and projected effectiveness of three vaccination strategies: i) immediate intervention with a 20-40% vaccine efficacy (VE) non-matched vaccine, ii) delayed intervention by developing a 50% VE clade-specific vaccine, and iii) immediate intervention with a non-matched vaccine replaced by a clade-specific vaccine when developed. Immediate vaccination with a non-clade matched vaccine, even with reduced efficacy, would prevent thousands of new infections in SF and millions in SA over 30 years. Vaccination with 50% VE delayed for five years needs six and 12 years in SA to break-even with immediate 20 and 30% VE vaccination, respectively, while not able to surpass the impact of immediate 40% VE vaccination over 30 years. Replacing a 30% VE with a 50% VE vaccine after 5 years reduces the HIV acquisition by 5% compared to delayed vaccination. The immediate use of an HIV vaccine with reduced VE in high risk communities appears desirable over a short time line but higher VE should be the pursued to achieve strong long-term impact. Our analysis illustrates the importance of developing surrogate markers (correlates of protection) to allow bridging types of immunogenicity studies to support more rapid assessment of clade specific vaccines.
Frew, Paula M.; Macias, Wendy; Chan, Kayshin; Harding, Ashley C.
During the past two decades of the HIV/AIDS pandemic, several recruitment campaigns were designed to generate community involvement in preventive HIV vaccine clinical trials. These efforts utilized a blend of advertising and marketing strategies mixed with public relations and community education approaches to attract potential study participants to clinical trials (integrated marketing communications). Although more than 30,000 persons worldwide have participated in preventive HIV vaccine studies, no systematic analysis of recruitment campaigns exists. This content analysis study was conducted to examine several United States and Canadian recruitment campaigns for one of the largest-scale HIV vaccine trials to date (the “Step Study”). This study examined persuasive features consistent with the Elaboration Likelihood Model (ELM) including message content, personal relevance of HIV/AIDS and vaccine research, intended audiences, information sources, and other contextual features. The results indicated variation in messages and communication approaches with gay men more exclusively targeted in these regions. Racial/ethnic representations also differed by campaign. Most of the materials promote affective evaluation of the information through heuristic cueing. Implications for subsequent campaigns and research directions are discussed. PMID:19609373
Frew, Paula M; Macias, Wendy; Chan, Kayshin; Harding, Ashley C
During the past two decades of the HIV/AIDS pandemic, several recruitment campaigns were designed to generate community involvement in preventive HIV vaccine clinical trials. These efforts utilized a blend of advertising and marketing strategies mixed with public relations and community education approaches to attract potential study participants to clinical trials (integrated marketing communications). Although more than 30,000 persons worldwide have participated in preventive HIV vaccine studies, no systematic analysis of recruitment campaigns exists. This content analysis study was conducted to examine several United States and Canadian recruitment campaigns for one of the largest-scale HIV vaccine trials to date (the "Step Study"). This study examined persuasive features consistent with the Elaboration Likelihood Model (ELM) including message content, personal relevance of HIV/AIDS and vaccine research, intended audiences, information sources, and other contextual features. The results indicated variation in messages and communication approaches with gay men more exclusively targeted in these regions. Racial/ethnic representations also differed by campaign. Most of the materials promote affective evaluation of the information through heuristic cueing. Implications for subsequent campaigns and research directions are discussed.
Kamali, Anatoli; Price, Matt A.; Lakhi, Shabir; Karita, Etienne; Inambao, Mubiana; Sanders, Eduard J.; Anzala, Omu; Latka, Mary H.; Bekker, Linda-Gail; Kaleebu, Pontiano; Asiki, Gershim; Ssetaala, Ali; Ruzagira, Eugene; Allen, Susan; Farmer, Paul; Hunter, Eric; Mutua, Gaudensia; Makkan, Heeran; Tichacek, Amanda; Brill, Ilene K.; Fast, Pat; Stevens, Gwynn; Chetty, Paramesh; Amornkul, Pauli N.; Gilmour, Jill
HIV epidemiology informs prevention trial design and program planning. Nine clinical research centers (CRC) in sub-Saharan Africa conducted HIV observational epidemiology studies in populations at risk for HIV infection as part of an HIV prevention and vaccine trial network. Annual HIV incidence ranged from below 2% to above 10% and varied by CRC and risk group, with rates above 5% observed in Zambian men in an HIV-discordant relationship, Ugandan men from Lake Victoria fishing communities, men who have sex with men, and several cohorts of women. HIV incidence tended to fall after the first three months in the study and over calendar time. Among suspected transmission pairs, 28% of HIV infections were not from the reported partner. Volunteers with high incidence were successfully identified and enrolled into large scale cohort studies. Over a quarter of new cases in couples acquired infection from persons other than the suspected transmitting partner. PMID:25602351
Kamali, Anatoli; Price, Matt A; Lakhi, Shabir; Karita, Etienne; Inambao, Mubiana; Sanders, Eduard J; Anzala, Omu; Latka, Mary H; Bekker, Linda-Gail; Kaleebu, Pontiano; Asiki, Gershim; Ssetaala, Ali; Ruzagira, Eugene; Allen, Susan; Farmer, Paul; Hunter, Eric; Mutua, Gaudensia; Makkan, Heeran; Tichacek, Amanda; Brill, Ilene K; Fast, Pat; Stevens, Gwynn; Chetty, Paramesh; Amornkul, Pauli N; Gilmour, Jill
HIV epidemiology informs prevention trial design and program planning. Nine clinical research centers (CRC) in sub-Saharan Africa conducted HIV observational epidemiology studies in populations at risk for HIV infection as part of an HIV prevention and vaccine trial network. Annual HIV incidence ranged from below 2% to above 10% and varied by CRC and risk group, with rates above 5% observed in Zambian men in an HIV-discordant relationship, Ugandan men from Lake Victoria fishing communities, men who have sex with men, and several cohorts of women. HIV incidence tended to fall after the first three months in the study and over calendar time. Among suspected transmission pairs, 28% of HIV infections were not from the reported partner. Volunteers with high incidence were successfully identified and enrolled into large scale cohort studies. Over a quarter of new cases in couples acquired infection from persons other than the suspected transmitting partner.
Dhalla, Shayesta; Poole, Gary
HIV vaccine preparedness studies (VPS) are important precursors to HIV vaccine trials. As well, they contribute to an understanding of motivators and barriers for participation in hypothetical HIV vaccine trials. Motivators can take the form of altruism and a desire for social benefits. Perceived personal benefits, including psychological, personal, and financial well-being, may also motivate participation. The authors performed a systematic review of HIV VPS using the Cochrane Database for Systematic Reviews, Medline, PubMed, Embase, and Google Scholar. The authors independently searched the literature for individual HIV VPS that examined motivators of participation in a hypothetical HIV vaccine trial, using the same search strategy. As the denominators employed in the literature varied across studies, the denominators were standardized to the number of respondents per survey item, regardless of their willingness to participate (WTP) in an HIV vaccine trial. The authors retrieved eight studies on social benefits (i.e., altruism) and 11 studies on personal benefits conducted in the Organization for Economic Co-operation and Development (OECD) countries, as well as 19 studies on social benefits and 20 studies on personal benefits in the non-OECD countries. Various different forms of altruism were found to be the major motivators for participation in an HIV vaccine trial in both the OECD and the non-OECD countries. In a large number of studies, protection from HIV was cited as a personal motivator for participation in a hypothetical HIV vaccine trial in the OECD and the non-OECD countries. Knowledge of motivators can inform and target recruitment for HIV vaccine trials, although it must be remembered that hypothetical motivators may not always translate into motivators in an actual vaccine trial.
Cervical cancer can be prevented with HPV vaccines. NCI-supported researchers helped establish HPV as a cause of cervical cancer. They also helped create the first HPV vaccines, were involved in the vaccine trials, and contribute to ongoing studies.
Korber, Bette; Hraber, Peter Thomas; Wagh, Kshitij; ...
In this study, a key unresolved challenge for developing an effective HIV-1 vaccine is the discovery of strategies to elicit immune responses that are able to cross-protect against a significant fraction of the diverse viruses that are circulating worldwide. Here, we summarize some of the immunological implications of HIV-1 diversity, and outline the rationale behind several polyvalent vaccine design strategies that are currently under evaluation. Vaccine-elicited T-cell responses, which contribute to the control of HIV-1 in natural infections, are currently being considered in both prevention and treatment settings. Approaches now in preclinical and human trials include full proteins in novelmore » vectors, concatenated conserved protein regions, and polyvalent strategies that improve coverage of epitope diversity and enhance the cross-reactivity of responses. While many barriers to vaccine induction of broadly neutralizing antibody (bNAb) responses remain, epitope diversification has emerged as both a challenge and an opportunity. Recent longitudinal studies have traced the emergence of bNAbs in HIV-1 infection, inspiring novel approaches to recapitulate and accelerate the events that give rise to potent bNAb in vivo. In this review, we have selected two such lineage-based design strategies to illustrate how such in-depth analysis can offer conceptual improvements that may bring us closer to an effective vaccine.« less
Schiffner, Torben; Sattentau, Quentin J; Dorrell, Lucy
The focus of most current HIV-1 vaccine development is on antibody-based approaches. This is because certain antibody responses correlated with protection from HIV-1 acquisition in the RV144 phase III trial, and because a series of potent and broad spectrum neutralizing antibodies have been isolated from infected individuals. Taken together, these two findings suggest ways forward to develop a neutralizing antibody-based vaccine. However, understanding of the correlates of protection from disease in HIV-1 and other infections strongly suggests that we should not ignore CTL-based research. Here we review recent progress in the field and highlight the challenges implicit in HIV-1 vaccine design and some potential solutions.
Rubens, Muni; Ramamoorthy, Venkataraghavan; Saxena, Anshul; Shehadeh, Nancy; Appunni, Sandeep
HIV/AIDS is a leading cause of mortality and morbidity worldwide. In spite of successful interventions and treatment protocols, an HIV vaccine would be the ultimate prevention and control strategy. Ever since identification of HIV/AIDS, there have been meticulous efforts for vaccine development. The specific aim of this paper is to review recent vaccine efficacy trials and associated advancements and discuss the current challenges and future directions. Recombinant DNA technologies greatly facilitated development of many viral products which were later incorporated into vectors for effective vaccines. Over the years, a number of scientific approaches have gained popularity and include the induction of neutralizing antibodies in late 1980s, induction of CD8 T cell in early 1990s, and combination approaches currently. Scientists have hypothesized that stimulation of right sequences of somatic hypermutations could induce broadly reactive neutralizing antibodies (bnAbs) capable of effective neutralization and viral elimination. Studies have shown that a number of host and viral factors affect these processes. Similarly, eliciting specific CD8 T cells immune responses through DNA vaccines hold future promises. In summary, future studies should focus on the continuous fight between host immune responses and ever-evasive viral factors for effective vaccines. PMID:26579546
Rappuoli, Rino; Aderem, Alan
Acquired immune deficiency syndrome (AIDS), malaria and tuberculosis collectively cause more than five million deaths per year, but have nonetheless eluded conventional vaccine development; for this reason they represent one of the major global public health challenges as we enter the second decade of the twenty-first century. Recent trials have provided evidence that it is possible to develop vaccines that can prevent infection by human immunodeficiency virus (HIV) and malaria. Furthermore, advances in vaccinology, including novel adjuvants, prime-boost regimes and strategies for intracellular antigen presentation, have led to progress in developing a vaccine against tuberculosis. Here we discuss these advances and suggest that new tools such as systems biology and structure-based antigen design will lead to a deeper understanding of mechanisms of protection which, in turn, will lead to rational vaccine development. We also argue that new and innovative approaches to clinical trials will accelerate the availability of these vaccines.
Newman, Peter A.; Seiden, Danielle S.; Roberts, Kathleen J.; Kakinami, Lisa; Duan, Naihua
Existing knowledge and beliefs related to HIV vaccines provide an important basis for the development of risk communication messages to support future HIV vaccine dissemination. This study explored HIV vaccine mental models among adults from segments of the population disproportionately affected by HIV/AIDS. Nine focus groups were conducted with…
West, Anthony P.; Scharf, Louise; Scheid, Johannes F.; Klein, Florian; Bjorkman, Pamela J.; Nussenzweig, Michel C.
Despite 30 years of effort, there is no effective vaccine for HIV-1. However, antibodies can prevent HIV-1 infection in humanized mice and macaques when passively transferred. New single-cell-based methods have uncovered many broad and potent donor-derived antibodies, and structural studies have revealed the molecular bases for their activities. The new data suggest why such antibodies are difficult to elicit and inform HIV-1 vaccine development efforts. In addition to protecting against infection, the newly identified antibodies can suppress active infections in mice and macaques, suggesting they could be valuable additions to anti-HIV-1 therapies and to strategies to eradicate HIV-1 infection. PMID:24529371
Cooper, Curtis; Thorne, Anona
Clinical experience suggests Oculorespiratory Syndrome (ORS) following influenza vaccination is rare in HIV but this is not well evaluated. We assessed ORS incidence in a randomized influenza vaccine trial of HIV participants. The overall incidence was 0.8% suggesting that influenza vaccine ORS incidence is reduced in HIV.
Hoffmann, Dieter; Seebach, Judith; Cosma, Antonio; Goebel, Frank D; Strimmer, Korbinian; Schätzl, Hermann M; Erfle, Volker
With HIV persisting lifelong in infected persons, therapeutic vaccination is a novel alternative concept to control virus replication. Even though CD8 and CD4 cell responses to such immunizations have been demonstrated, their effects on virus replication are still unclear. In view of this fact, we studied the impact of a therapeutic vaccination with HIV nef delivered by a recombinant modified vaccinia Ankara vector on viral diversity. We investigated HIV sequences derived from chronically infected persons before and after therapeutic vaccination. Before immunization the mean +/- se pairwise variability of patient-derived Nef protein sequences was 0.1527 +/- 0.0041. After vaccination the respective value was 0.1249 +/- 0.0042, resulting in a significant (P<0.0001) difference between the two time points. The genes vif and 5'gag tested in parallel and nef sequences in control persons yielded a constant amino acid sequence variation. The data presented suggest that Nef immunization induced a selective pressure, limiting HIV sequence variability. To our knowledge this is the first report directly linking therapeutic HIV vaccination to decreasing diversity in patient-derived virus isolates.
Bart, Kenneth J.
While morbidity and mortality from vaccine preventable diseases have declined, some college students remain susceptible to measles, rubella, diptheria, tetanus, or polio. Colleges and universities have the opportunity to ensure protection of students, faculty, and employees by establishing and enforcing immunization requirements. (Author/DF)
Haase, Ashley T
In this introductory essay on the landscape of HIV prevention, my intent is to provide context for the subsequent topics discussed at the Symposium on Hormone Regulation of the Mucosal Environment in the female reproductive tract (FRT) and the Prevention of HIV infection: FRT immunity, mucosal microenvironment and HIV prevention, and the risk and impact of hormonal contraceptives on HIV transmission.
Alio, Amina P.; Fields, Sheldon D.; Humes, Damon L.; Bunce, Catherine A.; Wallace, Stephaun E.; Lewis, Cindi; Elder, Heather; Wakefield, Steven; Keefer, Michael C.
Men who sleep with men (MSM) and transgender individuals of color, the largest demographic in the House Ball community (HBC) are amongst the group at highest risk for HIV infection in the United States. The HBC have limited access to culturally appropriate HIV education. This study aimed to develop a partnership with HBC leaders to uncover strategies for increasing HIV prevention knowledge, including participation in HIV vaccine trials. To this end a research institution-community-HBC partnership was established. In-depth qualitative and quantitative data were collected from the 14 HBC leaders in western New York, revealing that knowledge of HIV and related vaccine trials was limited. Barriers to increasing HIV knowledge included fear of peer judgment, having inaccurate information about HIV, and lack of education. Among the HBC, community partnerships will further aid in the development of future HIV prevention programs and increase individuals’ willingness to participate in future HIV vaccine trials. PMID:25642120
Gu, Linlin; Li, Zan C; Krendelchtchikov, Alexandre; Krendelchtchikova, Valentina; Wu, Hongju; Matthews, Qiana L
Adenoviral vectors have been used for a variety of vaccine applications including cancer and infectious diseases. Traditionally, Ad-based vaccines are designed to express antigens through transgene expression of a given antigen. For effective vaccine development it is often necessary to express or present multiple antigens to the immune system to elicit an optimal vaccine as observed preclinically with mosaic/polyvalent HIV vaccines or malaria vaccines. Due to the wide flexibility of Ad vectors they are an ideal platform for expressing large amounts of antigen and/or polyvalent mosaic antigens. Ad vectors that display antigens on their capsid surface can elicit a robust humoral immune response, the "antigen capsid-incorporation" strategy. The adenoviral hexon protein has been utilized to display peptides in the majority of vaccine strategies involving capsid incorporation. Based on our abilities to manipulate hexon HVR2 and HVR5, we sought to manipulate HVR1 in the context of HIV antigen display for the first time ever. More importantly, peptide incorporation within HVR1 was utilized in combination with other HVRs, thus creating multivalent vectors. To date this is the first report where dual antigens are displayed within one Ad hexon particle. These vectors utilize HVR1 as an incorporation site for a seven amino acid region of the HIV glycoprotein 41, in combination with six Histidine incorporation within HVR2 or HVR5. Our study illustrates that these multivalent antigen vectors are viable and can present HIV antigen as well as His6 within one Ad virion particle. Furthermore, mouse immunizations with these vectors demonstrate that these vectors can elicit a HIV and His6 epitope-specific humoral immune response.
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Brown, Jennifer L.; Sales, Jessica M.; DiClemente, Ralph J.
Background Combination HIV prevention interventions that integrate efficacious behavioral and biomedical strategies offer the potential to reduce new HIV infections. Purpose We overview the efficacy data for three biomedical HIV prevention approaches: microbicides, pre-exposure prophylaxis (PrEP), and an HIV vaccination, review factors associated with differential acceptability and uptake of these methods, and suggest strategies to optimize the effectiveness and dissemination of combination HIV prevention approaches. Methods A narrative review was conducted highlighting key efficacy data for microbicides, PrEP, and an HIV vaccination and summarizing acceptability data for each of the three biomedical HIV prevention approaches. Recommendations for the integration and dissemination of combined behavioral and biomedical HIV prevention approaches are provided. Results To date, microbicides and an HIV vaccination have demonstrated limited efficacy for the prevention of HIV. However, PrEP has demonstrated efficacy in reducing HIV incident infections. A diverse array of factors influences both hypothetical willingness and actual usage of each biomedical prevention method. Conclusions Strategies to effectively integrate and evaluate combination HIV prevention interventions are urgently needed. PMID:25216985
Kim, Peter S; Read, Sarah W
HIV/AIDS is a global pandemic and is the leading infectious cause of death among adults. Although antiretroviral (ARV) therapy has dramatically improved the quality of life and increased the life expectancy of those infected with HIV, life-long suppressive treatment is required and a cure for HIV infection remains elusive; frequency of dosing and drug toxicity as well as the development of viral resistance pose additional limitations. Furthermore, preventative measures such as a vaccine or microbicide are urgently needed to curb the rate of new infections. The capabilities inherent to nanotechnology hold much potential for impact in the field of HIV treatment and prevention. This article reviews the potential for the multidisciplinary field of nanotechnology to advance the fields of HIV treatment and prevention.
Yu, Mingke; Vajdy, Michael
Importance of the field There are currently over thirty million people infected with HIV and there are no vaccines available to prevent HIV infections or disease. The genitourinary, rectal and oral mucosa are the mucosal HIV transmission routes. An effective vaccine that can induce both systemic and local mucosal immunity is generally accepted as a major means of protection against mucosal HIV transmission and AIDS. What the reader will gain Structure and cells that comprise the oral, vaginal and rectal mucosa pertaining to HIV transmission and vaccination strategies through each mucosal route to prevent mucosal and systemic infection will be discussed. Areas covered in this review Covering publications from 1980’s through 2010, mucosal transmission of HIV and current and previous approaches to vaccinations are discussed. Take home message Although oral transmission of HIV is far less common than vaginal and rectal transmissions, infections through this route do occur through oral sex as well as vertically from mother to child. Mucosal vaccination strategies against oral and other mucosal HIV transmissions are under intense research but the lack of consensus on immune correlates of protection and lack of safe and effective mucosal adjuvants and delivery systems hamper progress towards a licensed vaccine. PMID:20624114
de la Briére, Alice; Berenguerb, Marc; Destombesa, Christelle
Vaccines against hepatitisA and B are today available and effective. The prevention of hepatitis is thereby based on the reduction of the risk of infection, notably among drug users. France is experimenting with a supervised drug consumption room. For professionals, information, training and physical means of protection are essential to avoid contamination. The operating theatre is an example of a treatment area which is particularly concerned.
Wang, Qian; Bi, Wenwen; Zhu, Xiaojie; Li, Haoyang; Qi, Qianqian; Yu, Fei; Lu, Lu; Jiang, Shibo
A key barrier against developing preventive and therapeutic human immunodeficiency virus (HIV) vaccines is the inability of viral envelope glycoproteins to elicit broad and potent neutralizing antibodies. However, in the presence of fusion inhibitor enfuvirtide, we show that the nonneutralizing antibodies induced by the HIV type 1 (HIV-1) gp41 N-terminal heptad repeat (NHR) domain (N63) exhibit potent and broad neutralizing activity against laboratory-adapted HIV-1 strains, including the drug-resistant variants, and primary HIV-1 isolates with different subtypes, suggesting the potential of developing gp41-targeted HIV therapeutic vaccines.
Vaccines to prevent HIV remain desperately needed, but a number of challenges, including retroviral integration, establishment of anatomic reservoir sites, high sequence diversity, and heavy envelope glycosylation. have precluded development of a highly effective vaccine. DNA vaccines have been utilized as candidate HIV vaccines because of their ability to generate cellular and humoral immune responses, the lack of anti-vector response allowing for repeat administration, and their ability to prime the response to viral-vectored vaccines. Because the HIV epidemic has disproportionately affected the developing world, the favorable thermostability profile and relative ease and low cost of manufacture of DNA vaccines offer additional advantages. In vivo electroporation (EP) has been utilized to improve immune responses to DNA vaccines as candidate HIV-1 vaccines in standalone or prime-boost regimens with both proteins and viral-vectored vaccines in several animal models and, more recently, in human clinical trials. This chapter describes the preclinical and clinical development of candidate DNA vaccines for HIV-1 delivered by EP, including challenges to bringing this technology to the developing world.
Rolland, Morgane; Edlefsen, Paul T; Larsen, Brendan B; Tovanabutra, Sodsai; Sanders-Buell, Eric; Hertz, Tomer; deCamp, Allan C; Carrico, Chris; Menis, Sergey; Magaret, Craig A; Ahmed, Hasan; Juraska, Michal; Chen, Lennie; Konopa, Philip; Nariya, Snehal; Stoddard, Julia N; Wong, Kim; Zhao, Hong; Deng, Wenjie; Maust, Brandon S; Bose, Meera; Howell, Shana; Bates, Adam; Lazzaro, Michelle; O'Sullivan, Annemarie; Lei, Esther; Bradfield, Andrea; Ibitamuno, Grace; Assawadarachai, Vatcharain; O'Connell, Robert J; deSouza, Mark S; Nitayaphan, Sorachai; Rerks-Ngarm, Supachai; Robb, Merlin L; McLellan, Jason S; Georgiev, Ivelin; Kwong, Peter D; Carlson, Jonathan M; Michael, Nelson L; Schief, William R; Gilbert, Peter B; Mullins, James I; Kim, Jerome H
The RV144 trial demonstrated 31% vaccine efficacy at preventing human immunodeficiency virus (HIV)-1 infection. Antibodies against the HIV-1 envelope variable loops 1 and 2 (Env V1 and V2) correlated inversely with infection risk. We proposed that vaccine-induced immune responses against V1/V2 would have a selective effect against, or sieve, HIV-1 breakthrough viruses. A total of 936 HIV-1 genome sequences from 44 vaccine and 66 placebo recipients were examined. We show that vaccine-induced immune responses were associated with two signatures in V2 at amino acid positions 169 and 181. Vaccine efficacy against viruses matching the vaccine at position 169 was 48% (confidence interval 18% to 66%; P = 0.0036), whereas vaccine efficacy against viruses mismatching the vaccine at position 181 was 78% (confidence interval 35% to 93%; P = 0.0028). Residue 169 is in a cationic glycosylated region recognized by broadly neutralizing and RV144-derived antibodies. The predicted distance between the two signature sites (21 ± 7 Å) and their match/mismatch dichotomy indicate that multiple factors may be involved in the protection observed in RV144. Genetic signatures of RV144 vaccination in V2 complement the finding of an association between high V1/V2-binding antibodies and reduced risk of HIV-1 acquisition, and provide evidence that vaccine-induced V2 responses plausibly had a role in the partial protection conferred by the RV144 regimen.
Lee, Sung-Jae; Newman, Peter A.; Duan, Naihua; Cunningham, William E.
Background Decade-long delays in successful implementation of Hepatitis B vaccines and ongoing obstacles in HPV vaccine roll-out suggest the importance of an implementation science approach to prepare for the effective translation of future HIV vaccines from clinical trials into routine practice. The objective of this study wasto test HIV vaccine attitude items to develop reliable scales and to examine their association with HIV vaccine acceptability. Methods HIV vaccine attitude items were assessed as part of the L.A. VOICES survey, a large-scale study conducted among underserved residents of Los Angeles, to identify factors that may influence HIV vaccine acceptability. Participants (n=1,225) were randomly selected from public STD clinics, needle exchange sites and Latino community clinics using three-stage, venue-based time space sampling. Results Exploratory factor analysis across 20 items revealed four distinct factors—mistrust, HIV vaccine social concerns, risk compensation, and altruistic vaccination—with acceptable reliability coefficients for each subscale (Cronbach’s α range 0.61 – 0.84). We found no significant differences in reliability by gender or by vaccine acceptability. Risk compensation (Odds Ratio (OR) =1.49; 95% CI=[1.18, 1.89]; p=0.001) and altruistic vaccination (OR=1.40; 95% CI=[1.14, 1.71]; p=0.001) were significantly and positively associated with HIV vaccine acceptability. Conclusions We identified four HIV vaccine attitude scales with sound internal reliability parameters. In the aftermath of the first candidate vaccine to demonstrate efficacy against HIV infection, these scales may be helpful in bridging expectable research-to-practice gaps in future HIV vaccine dissemination among populations at risk. As HIV vaccine trials progress in the United States and globally, these measures also may be useful as a tool to assess and facilitate effective responses to community concerns about HIV vaccine trials and to target interventions
Ravert, Russell D.; Zimet, Gregory D.
Objective: To examine behavioral history, beliefs, and vaccine characteristics as predictors of HIV vaccine acceptability. Methods: Two hundred forty-five US under graduates were surveyed regarding their sexual history, risk beliefs, and likelihood of accepting hypothetical HIV vaccines. Results: Multivariate regression analysis indicated that…
van Haaren, Marlies M; van den Kerkhof, Tom L G M; van Gils, Marit J
So far, the development of a human immunodeficiency virus (HIV) vaccine has been unsuccessful. However, recent progress in the field of broadly neutralizing antibodies (bNAbs) has reinvigorated the search for an HIV vaccine. bNAbs develop in a minority of HIV infected individuals and passive transfer of these bNAbs to non-human primates provides protection from HIV infection. Studies in a number of HIV infected individuals on bNAb maturation alongside viral evolution and escape have shed light on the features important for bNAb elicitation. Here we review the observations from these studies, and how they influence the rational design of HIV vaccines.
Moodie, Zoe; Metch, Barbara; Bekker, Linda-Gail; Churchyard, Gavin; Nchabeleng, Maphoshane; Mlisana, Koleka; Laher, Fatima; Roux, Surita; Mngadi, Kathryn; Innes, Craig; Mathebula, Matsontso; Allen, Mary; Bentley, Carter; Gilbert, Peter B.; Robertson, Michael; Kublin, James; Corey, Lawrence; Gray, Glenda E.
Background The Phase 2b double-blinded, randomized Phambili/HVTN 503 trial evaluated safety and efficacy of the MRK Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine vs placebo in sexually active HIV-1 seronegative participants in South Africa. Enrollment and vaccinations stopped and participants were unblinded but continued follow-up when the Step study evaluating the same vaccine in the Americas, Caribbean, and Australia was unblinded for non-efficacy. Final Phambili analyses found more HIV-1 infections amongst vaccine than placebo recipients, impelling the HVTN 503-S recall study. Methods HVTN 503-S sought to enroll all 695 HIV-1 uninfected Phambili participants, provide HIV testing, risk reduction counseling, physical examination, risk behavior assessment and treatment assignment recall. After adding HVTN 503-S data, HIV-1 infection hazard ratios (HR vaccine vs. placebo) were estimated by Cox models. Results Of the 695 eligible, 465 (67%) enrolled with 230 from the vaccine group and 235 from the placebo group. 38% of the 184 Phambili dropouts were enrolled. Enrollment did not differ by treatment group, gender, or baseline HSV-2. With the additional 1286 person years of 503-S follow-up, the estimated HR over Phambili and HVTN 503-S follow-up was 1.52 (95% CI 1.08–2.15, p = 0.02, 82 vaccine/54 placebo infections). The HR was significant for men (HR = 2.75, 95% CI 1.49, 5.06, p = 0.001) but not for women (HR = 1.12, 95% CI 0.73, 1.72, p = 0.62). Conclusion The additional follow-up from HVTN 503-S supported the Phambili finding of increased HIV-1 acquisition among vaccinated men and strengthened the evidence of lack of vaccine effect among women. Trial Registration clinicaltrials.gov NCT00413725 SA National Health Research Database DOH-27-0207-1539 PMID:26368824
Wigfall, L T; Bynum, S A; Brandt, H M; Hébert, J R
Cervical cancer risk is increased among women living with HIV (WLH). Human papillomavirus (HPV) vaccination has been shown to be safe and immunogenic among WLH. We examined HPV vaccine awareness and HPV knowledge among WLH. This cross-sectional study collected data from 145 WLH between March 2011 and April 2012. An interviewer-administered survey assessed HPV vaccine awareness and knowledge. Stata/IC 13 was used to perform chi-square tests and multivariate logistic regression analyses. Our sample was 90 % non-Hispanic black and 64 % earned <$10,000/year. Few (38 %) had heard of the HPV vaccine. Half (50 %) knew that HPV caused cervical cancer. HPV vaccine awareness was ten times higher among WLH who knew HPV caused cervical cancer (OR = 10.17; 95 % CI 3.82-27.06). HPV vaccine awareness is low among WLH. Cancer prevention efforts aimed at raising awareness about the HPV vaccine and increasing knowledge about HPV are necessary first steps in reducing cervical cancer disparities among WLH.
... Resources Related Links Vaccines & Immunizations Rotavirus and the Vaccine (Drops) to Prevent It Language: English Español (Spanish) ... vaccine. Why should my child get the rotavirus vaccine? The rotavirus vaccine: Protects your child from rotavirus, ...
Ignatowicz, Lech; Mazurek, Jolanta; Leepiyasakulchai, Chaniya; Sköld, Markus; Hinkula, Jorma; Källenius, Gunilla; Pawlowski, Andrzej
Tuberculosis (TB) has emerged as the most prominent bacterial disease found in human immunodeficiency virus (HIV)-positive individuals worldwide. Due to high prevalence of asymptomatic Mycobacterium tuberculosis (Mtb) infections, the future HIV vaccine in areas highly endemic for TB will often be administrated to individuals with an ongoing Mtb infection. The impact of concurrent Mtb infection on the immunogenicity of a HIV vaccine candidate, MultiHIV DNA/protein, was investigated in mice. We found that, depending on the vaccination route, mice infected with Mtb before the administration of the HIV vaccine showed impairment in both the magnitude and the quality of antibody and T cell responses to the vaccine components p24Gag and gp160Env. Mice infected with Mtb prior to intranasal HIV vaccination exhibited reduced p24Gag-specific serum IgG and IgA, and suppressed gp160Env-specific serum IgG as compared to respective titers in uninfected HIV-vaccinated controls. Importantly, in Mtb-infected mice that were HIV-vaccinated by the intramuscular route the virus neutralizing activity in serum was significantly decreased, relative to uninfected counterparts. In addition mice concurrently infected with Mtb had fewer p24Gag-specific IFN-γ-expressing T cells and multifunctional T cells in their spleens. These results suggest that Mtb infection might interfere with the outcome of prospective HIV vaccination in humans. PMID:22848444
Whaley, Kevin J.; Mayer, Kenneth H.
Human immunodeficiency virus (HIV) may be transmitted through either cell-free virions or leukocytes harboring intracellular HIV in bodily fluids. In recent years, the early initiation of combination antiretroviral therapy leading to virological suppression has resulted in decreased HIV transmission to uninfected partners. Additionally, the efficacy of primary chemoprophylaxis with oral or topical antiretroviral regimens containing tenofovir (with or without emtricitabine) has been demonstrated. However, the efficacy of these approaches may be compromised by suboptimal adherence, decreased drug concentrations in mucosal compartments in women, and genital inflammation. Furthermore, in vitro studies on the effects of tenofovir on cell-associated HIV transmission have produced conflicting results. Preclinical studies suggest that combination preventive approaches may be most effective in stopping the transmission of HIV after mucosal exposure. Since the development of antibodies were found to correlate with protection in the only effective HIV vaccine trial, the administration of preformed mucosal and systemic antibodies may inform the development of safe and effective antibody-based oral, topical, and/or systemic preexposure prophylaxis agents and provide guidance in the development of HIV vaccines that effectively block cell-associated HIV transmission. PMID:25414423
Haynes, Barton F; Kelsoe, Garnett; Harrison, Stephen C; Kepler, Thomas B
Failure of immunization with the HIV-1 envelope to induce broadly neutralizing antibodies against conserved epitopes is a major barrier to producing a preventive HIV-1 vaccine. Broadly neutralizing monoclonal antibodies (BnAbs) from those subjects who do produce them after years of chronic HIV-1 infection have one or more unusual characteristics, including polyreactivity for host antigens, extensive somatic hypermutation and long, variable heavy-chain third complementarity-determining regions, factors that may limit their expression by host immunoregulatory mechanisms. The isolation of BnAbs from HIV-1-infected subjects and the use of computationally derived clonal lineages as templates provide a new path for HIV-1 vaccine immunogen design. This approach, which should be applicable to many infectious agents, holds promise for the construction of vaccines that can drive B cells along rare but desirable maturation pathways.
Rivas-Santiago, Bruno; Cervantes-Villagrana, Alberto R
It is estimated that there are approximately eight million new cases of active tuberculosis (TB) worldwide annually. There is only 1 vaccine available for prevention: bacillus Calmette-Guérin (BCG). This has variable efficacy and is only protective for certain extrapulmonary TB cases in children, therefore new strategies for the creation of novel vaccines have emerged. One of the promising approaches is the DNA vaccine, used as a direct vaccination or as a prime-boost vaccine. This review describes the experimental data obtained during the design of DNA vaccines for TB.
Haase, Ashley T
Measures to prevent sexual mucosal transmission of human immunodeficiency virus (HIV)-1 are urgently needed to curb the growth of the acquired immunodeficiency syndrome (AIDS) pandemic and ultimately bring it to an end. Studies in animal models and acute HIV-1 infection reviewed here reveal potential viral vulnerabilities at the mucosal portal of entry in the earliest stages of infection that might be most effectively targeted by vaccines and microbicides, thereby preventing acquisition and averting systemic infection, CD4 T-cell depletion and pathologies that otherwise rapidly ensue.
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When HIV was discovered and established as the cause of AIDS in 1983–1984, many people believed that a vaccine would be rapidly developed. However, 30 years have passed and we are still struggling to develop an elusive vaccine. In trying to achieve that goal, different scientific paradigms have been explored. Although major progress has been made in understanding the scientific basis for HIV vaccine development, efficacy trials have been critical in moving the field forward. Major lessons learned are: the development of an HIV vaccine is an extremely difficult challenge; the temptation of just following the fashion should be avoided; clinical trials are critical, especially large-scale efficacy trials; HIV vaccine research will require long-term commitment; and sustainable collaborations are needed to accelerate the development of an HIV vaccine. Concrete actions must be implemented with the sense of urgency imposed by the severity of the AIDS epidemic. PMID:26344345
Filice, G A; Pomeroy, C
Secondary infectious diseases contribute substantially to morbidity and mortality of people infected with human immunodeficiency virus (HIV). The authors developed comprehensive, practical recommendations for prevention of infectious complications in HIV-infected people. Recommendations are concerned with the pathogens that are more common or more severe in HIV-infected people. Several infectious complications can be prevented by avoiding ingestion of contaminated food or water. Zoonoses can be prevented by precautions to be taken in contacts with animals. The risk of several fungal diseases can be reduced if activities likely to lead to inhalation of spores are avoided. HIV-infected people should be advised how to lower adverse health effects of travel, especially international travel. The potential for infectious complications of sexual activity and illicit drug use should be stressed, and recommendations to reduce the risk are discussed. Recommendations for use of vaccines in HIV-infected people are reviewed. Blood CD4+ lymphocyte concentrations, tuberculin skin testing, Toxoplasma serology, and sexually transmitted disease screening should be performed in certain subsets of HIV-infected people. Guidelines for chemoprophylaxis against Pneumocystis carinii and tuberculosis are presented. Recent data suggest that intravenous immunoglobulin therapy may prevent bacterial infections in HIV-infected children. PMID:1910184
Smith, Kendall A; Andjelic, Sofija; Popmihajlov, Zoran; Kelly-Rossini, Liza; Sass, Aquanette; Lesser, Martin; Benkert, Steven; Waters, Cory; Ruitenberg, Joyce; Bellman, Paul
Objectives: To determine whether immunotherapy of chronic HIV-1 infection can prevent or attenuate viremia upon antiviral discontinuation. Design: This was a Phase II randomized, partially double blinded, 2×2 factorial study of three steps of 12 wk/step. Step I involved four groups: (1) vaccine placebo, (2) vaccine (ALVAC, vCP1452), (3) placebo + interleukin 2 (IL-2), and (4) vaccine + IL-2. Step II involved a 12-wk diagnostic treatment interruption (DTI). Step III involved an extension of the DTI for an additional 12 wk. Setting: The Weill-Cornell General Clinical Research Center. Participants: Chronically infected HIV-1 positive adults with undetectable HIV-1 levels and > 400 CD4+ T cells/μl. Interventions An HIV canarypox vaccine (vCP1452) and vaccine placebo, administered every 4 wk for four doses, and low-dose IL-2 administered daily for 12–24 wk. Outcome measures: Primary endpoints: (1) Proportion of participants with undetectable plasma HIV RNA during trial Step II, (2) mean log10 HIV RNA copies/ml ([HIV]) from weeks 21–25, and (3) proportion of individuals eligible for trial Step III. Results: 44 participants were randomized, but 16 withdrew or were withdrawn before completing Step II. As all participants underwent viral relapse in Step II, the study was terminated after 28 participants completed Step II. Among the four groups, there was no difference in mean [HIV] or the proportion of individuals with < log10 4.48 HIV; no difference between the mean [HIV] of the two groups that received ALVAC (n = 17) versus placebo (n = 11); and no significant difference between the mean [HIV] of the two groups that received IL-2 (n = 11) versus placebo (n = 17). Conclusions: Neither ALVAC (vCP1452) nor low-dose daily IL-2 nor their combination prevented the relapse of viremia upon discontinuation of antiviral therapy. PMID:17260026
Flash, Charlene; Krakower, Douglas; Mayer, Kenneth H.
With an estimated 2.6 million new HIV infections diagnosed annually, the world needs new prevention strategies to partner with condom use, harm reduction approaches for injection drug users, and male circumcision. Antiretrovirals can reduce the risk of mother-to-child HIV transmission and limit HIV acquisition after occupational exposure. Macaque models and clinical trials demonstrate efficacy of oral or topical antiretrovirals used prior to HIV exposure to prevent HIV transmission, ie pre-exposure prophylaxis (PrEP). Early initiation of effective HIV treatment in serodiscordant couples results in a 96% decrease in HIV transmission. HIV testing to determine serostatus and identify undiagnosed persons is foundational to these approaches. The relative efficacy of different approaches, adherence, cost and long-term safety will affect uptake and impact of these strategies. Ongoing research will help characterize the role for oral and topical formulations and help quantify potential benefits in sub-populations at risk for HIV acquisition. PMID:22351302
French, Neil; Gordon, Stephen B; Mwalukomo, Thandie; White, Sarah A; Mwafulirwa, Gershom; Longwe, Herbert; Mwaiponya, Martin; Zijlstra, Eduard E; Molyneux, Malcolm E; Gilks, Charles F
Background: Streptococcus pneumoniae is a leading and serious co-infection of HIV-infected adults, particularly in Africa. Prevention of disease by vaccination with the current 23-valent polysaccharide vaccine is sub-optimal. Protein conjugate vaccines offer a further option for protection but no data exist on their clinical efficacy in any adult population. Methods: We conducted a double-blind randomized placebo-controlled clinical efficacy trial of the seven-valent conjugate pneumococcal vaccine in predominantly HIV-infected Malawian adults who had recovered from documented invasive pneumococcal disease (IPD). Vaccine was given as a two dose schedule four weeks apart. The primary end-point was a further episode of IPD caused by a vaccine-serotype or serotype-6A (VST/6A) pneumococcus. Results: Between February 2003 and October 2007, 496 individuals (44% male, 88% HIV seropositive) were followed for 798 person years of observation. There were 67 IPD events in 52 individuals, all in the HIV infected sub-group. There were 24 VST/6A events (19 VST, five 6A) in 24 participants, 5 in vaccine and 19 in the placebo recipients, a vaccine efficacy of 74% (95% CI 30% - 90%). There were 73 deaths in the vaccine arm and 63 in the placebo arm, Hazard Ratio 1.18 (95% confidence intervals 0.84 -1.66). Compared to placebo, serious adverse events were significantly lower (3 vs 17, p = 0.002) and minor adverse events significantly higher (41 vs 13, p = 0.003 ) in vaccine recipients. Conclusions: The seven-valent pneumococcal conjugate vaccine protects HIV infected adults from recurrent IPD of vaccine serotype or serotype 6A. PMID:20200385
Pinkerton, Steven D.; Abramson, Paul R.
Biomedical, logistic, economic, social, and psychosocial issues related to the successful distribution and use of a vaccine for human immunodeficiency virus (HIV) are reviewed. A mathematical model is introduced as an aid in conceptualizing these issues. The HIV vaccine should be seen as an adjunct to behavioral modification. (SLD)
Cutler, Blayne; Justman, Jessica
Worldwide, nearly half of all individuals living with HIV are now women, who acquire the virus largely by heterosexual exposure. With an HIV vaccine likely to be years away, topical microbicide formulations applied vaginally or rectally are being investigated as another strategy for HIV prevention. A review of preclinical and clinical research on the development of microbicides formulated to prevent vaginal HIV transmission yielded 118 studies: 73 preclinical and 45 clinical. Preclinical research included in-vitro assays and cervical explant models, as well as animal models. Clinical research included phase I and II/IIb safety studies, and phase III efficacy studies. Whereas most phase I and phase II clinical trials have found microbicide compounds to be safe and well tolerated, phase III trials completed to date have not demonstrated efficacy in preventing HIV transmission. Topical microbicides are grouped into five classes of agents, based on where they disrupt the pathway of sexual transmission of HIV. These classes include surfactants/membrane disruptors, vaginal milieu protectors, viral entry inhibitors, reverse transcriptase inhibitors, and a fifth group whose mechanism is unknown. The trajectory of microbicide development has been toward agents that block more specific virus—host cell interactions. Microbicide clinical trials face scientifically and ethically complex issues, such as the choice of placebo gel, the potential for viral resistance, and the inclusion of HIV-infected participants. Assessment of combination agents will most likely advance this field of research. PMID:18992405
Globally, $200-250 million/year are devoted to HIV vaccine research. Most of those funds pay for basic research rather than product development. Moreover, most of the funds are aimed at the HIV strain commonly found in the US and Europe, and not at the strains common to Africa and other developing countries. While US President Bill Clinton set in 1997 a 10-year target for the development of an HIV vaccine, that target date is looking increasingly unlikely. International vaccine and pharmaceutical companies typically drive vaccine research and development. However, concern over the ultimate profitability of developing and marketing an HIV vaccine, and the fear of major litigation should an eventual vaccine go awry have caused such firms to shy away from investing large amounts of money into HIV vaccine development. These companies somehow have to be attracted back into the field. A World Bank special task force is slated to present its report by mid-1999 on possible funding mechanisms to promote HIV vaccine development. It remains to be resolved whether public funds could and should be used, perhaps through a pooled international vaccine development fund. 2 new International AIDS Vaccine Initiative projects are described.
Chin'ombe, Nyasha; Ruhanya, Vurayai
HIV/AIDS is an important public health problem globally. An affordable, easy-to-deliver and protective HIV vaccine is therefore required to curb the pandemic from spreading further. Recombinant Salmonella bacteria can be harnessed to vector HIV antigens or DNA vaccines to the immune system for induction of specific protective immunity. These are capable of activating the innate, humoral and cellular immune responses at both mucosal and systemic compartments. Several studies have already demonstrated the utility of live recombinant Salmonella in delivering expressed foreign antigens as well as DNA vaccines to the host immune system. This review gives an overview of the studies in which recombinant Salmonella bacteria were used to vector HIV/AIDS antigens and DNA vaccines. Most of the recombinant Salmonella-based HIV/AIDS vaccines developed so far have only been tested in animals (mainly mice) and are yet to reach human trials.
Neumann, Mary Spink; Finlayson, Teresa J; Pitts, Nicole L; Keatley, JoAnne
Transgender persons are at high risk for HIV infection, but prevention efforts specifically targeting these people have been minimal. Part of the challenge of HIV prevention for transgender populations is that numerous individual, interpersonal, social, and structural factors contribute to their risk. By combining HIV prevention services with complementary medical, legal, and psychosocial services, transgender persons' HIV risk behaviors, risk determinants, and overall health can be affected simultaneously. For maximum health impact, comprehensive HIV prevention for transgender persons warrants efforts targeted to various impact levels-socioeconomic factors, decision-making contexts, long-lasting protections, clinical interventions, and counseling and education. We present current HIV prevention efforts that reach transgender persons and present others for future consideration.
Mena, G; García-Basteiro, A L; Bayas, J M
Hepatitis B and A account for considerable morbidity and mortality worldwide. Immunization is the most effective means of preventing hepatitis B and A. However, the immune response to both hepatitis vaccines seems to be reduced in HIV-infected subjects. The aim of this review was to analyze the immunogenicity, safety, long-term protection and current recommendations of hepatitis B and A vaccination among HIV-infected adults. The factors most frequently associated with a deficient level of anti-HBs or IgG anti-HAV after vaccination are those related to immunosuppression (CD4 level and HIV RNA viral load) and to the frequency of administration and/or the amount of antigenic load per dose. The duration of the response to both HBV and HAV vaccines is associated with suppression of the viral load at vaccination and, in the case of HBV vaccination, with a higher level of antibodies after vaccination. In terms of safety, there is no evidence of more, or different, adverse effects compared with HIV-free individuals. Despite literature-based advice on the administration of alternative schedules, revaccination after the failure of primary vaccination, and the need for periodic re-evaluation of antibody levels, few firm recommendations are found in the leading guidelines.
Cicala, Claudia; Nawaz, Fatima; Jelicic, Katija; Arthos, James; Fauci, Anthony S
Although extraordinary progress has been made in the treatment and prevention of HIV infection, the AIDS pandemic continues to rage globally with 2.1 million infections and 1.6 million AIDS-related deaths reported in 2013. Until an effective vaccine is developed, new strategies for treatment and prevention are needed. Regarding the prevention of HIV infection, a major focus of prevention research in general and vaccine research in particular involves the interaction of the HIV-1 envelope protein gp120 with cell-surface receptors, with the hope that a greater understanding of these interactions will lead to the development of novel strategies aimed at preventing and even treating HIV-1 infection. Particular attention has been directed toward gaining a more precise understanding of the early events in transmission focusing on that critical window of time when HIV first establishes infection in the host. Here we describe some of the recent findings involving HIV-1 envelope interactions with cell surface receptors that are relevant to transmission and which may represent new opportunities to develop strategies to prevent HIV infection.
Aziz, M; Kessler, H; Huhn, G
Identification of perceptions about herpes zoster (HZ) disease, vaccine effectiveness and safety, and vaccine recommendations may impact immunization practices of physicians for HIV-infected patients. A survey was used to quantify knowledge of HZ as well as determine physician immunization perceptions and practices. There were 272/1700 respondents (16%). Correct answers for the incidence of varicella zoster virus (VZV) infection in adults and incidence of HZ in HIV-infected patients were recorded by 14% and 10% of providers, respectively. Providers reported poor knowledge of the incidence of disease recurrence in HIV-infected patients (41% correct), potency of HZ vaccine (47.5% correct) and mechanism of protection against reactivation of VZV (66% correct). Most (88%) agreed that HZ was a serious disease, and 73% believed that the burden of disease made vaccination important. A majority (75%) did not vaccinate HIV patients with HZ vaccine regardless of antiretroviral therapy status. Barriers to administration included safety concerns, concern that vaccine would not prevent HZ, risk of HZ dissemination, reimbursement issues and lack of Infectious Diseases Society of America (IDSA) guidelines. Only 38% of providers agreed that CDC guidelines were clear and 50% believed that clinical trials were needed prior to use of HZ vaccine in HIV-infected patients. Education about HZ is needed among HIV providers. Providers perceived vaccination as important, but data on vaccine safety and clear guidance from the CDC on this issue are lacking.
Kitchen, A D; Hewitt, P E
We report two instances of human immunodeficiency virus (HIV) serological screening reactivity in blood donations which were subsequently determined to be due to donor participation in HIV vaccine trials. Both donations were screen reactive with atypical patterns on confirmation; no definitive conclusion could be given for either donor. Subsequent questioning identified that both donors had been involved in HIV vaccine trials. In both cases the screening and confirmation identified the presence of HIV antibodies, although vaccine induced. While clinical trials of vaccines are important, the implications of some need careful consideration if they are not to adversely impact other areas of healthcare.
Koenig, Helen C; Garland, Joseph M; Weissman, Drew; Mounzer, Karam
Vaccination has been one of our most powerful tools to decrease morbidity and mortality from infectious diseases in the last century. It is critical to understand the evolving safety and efficacy data for vaccines in HIV-infected individuals as the number of people living with HIV in the United States and globally continues to increase. The quadrivalent human papillomavirus vaccine and the herpes zoster vaccine are newly licensed in the general population, and several studies have recently been published on the safety and efficacy of these vaccines in HIV populations. This manuscript reviews recent data for the vaccines most commonly administered in HIV patients and incorporates these data into our body of knowledge about the safety and efficacy of vaccines in this population. In addition, patient factors that predict response for each vaccine are discussed. Given the great burden of human papillomavirus and herpes zoster in HIV patients, we discuss the benefits and the challenges of vaccinating HIV patients with the human papillomavirus and herpes zoster vaccines. This review provides information that clinicians need to make real-time decisions in the absence of large-scale trials in the HIV population.
Muessig, Kathryn E.; Cohen, Myron S.
Serodiscordant couples play an important role in maintaining the global HIV epidemic. This review summarizes biobehavioral and biomedical HIV prevention options for serodiscordant couples focusing on advances in 2013 and 2014, including World Health Organization guidelines and best-evidence for couples counseling, couples-based interventions, and the use of antiviral agents for prevention. In the past few years marked advances have been made in HIV prevention for serodiscordant couples and numerous ongoing studies are continuously expanding HIV prevention tools, especially in the area of pre-exposure prophylaxis. Uptake and adherence to antiviral therapy remains a key challenge. Additional research is needed to develop evidence-based interventions for couples, and especially for male-male couples. Randomized trials have demonstrated the prevention benefits of antiretroviral-based approaches among serodiscordant couples; however, residual transmission observed in recognized serodiscordant couples represents an important and resolvable challenge in HIV prevention. PMID:25145645
Voytek, Chelsea D; Jones, Kevin T; Metzger, David S
Efficacy studies of investigational HIV vaccines require enrollment of individuals at 'high risk' for HIV. This paper examines participation in HIV vaccine trials among women at 'high risk' for HIV acquisition. In-depth interviews were conducted with 17 African-American women who use crack cocaine and/or exchange sex for money/drugs to elicit attitudes toward medical research and motivators and deterrents to HIV vaccine trial participation. Interviews were digitally recorded and transcribed; data were coded and compiled into themes. Most women expressed favorable attitudes toward medical research in general. Motivators for trial participation included compensation; personal benefits including information, social services, and the possibility that the trial vaccine could prevent HIV; and altruism. Deterrents included: dislike of needles; distrust; concern about future consequences of participating. In addition, contingencies, care-giving responsibilities, and convenience issues constituted barriers which could impede participation. Respondents described varied, complex perspectives, and individual cases illustrate how these themes played out as women contemplated trial participation. Understanding factors which influence vaccine research participation among women at 'high risk' can aid sites to tailor recruitment procedures to local contexts. Concerns about future reactions can be addressed through sustained community education. Convenience barriers can be ameliorated by providing rides to study visits when necessary, and/or conducting study visits in accessible neighborhood locations. Women in this sample thought carefully about enrolling in HIV vaccine trials given the structural constraints within which they lived. Further research is needed regarding structural factors which influence personal agency and individuals' thinking about research participation.
Reducing the incidence of HIV infection continues to be a crucial public health priority in the United States, especially among populations at elevated risk such as men who have sex with men, transgender women, people who inject drugs, and racial and ethnic minority communities. Although most HIV prevention efforts to date have focused on changing risky behaviors, the past decade has yielded efficacious new biomedical technologies designed to prevent infection, such as the prophylactic use of antiretroviral drugs and the first indications of an efficacious vaccine. Access to prevention technologies will be a significant part of the next decade’s response to HIV, and advocates are mobilizing to achieve more widespread use of these interventions. These breakthroughs, however, arrive at a time of escalating healthcare costs; health insurance coverage therefore raises pressing new questions about priority-setting and the allocation of responsibility for public health. The goals of this Article are to identify legal challenges and potential solutions for expanding access to biomedical HIV prevention through health insurance coverage. This Article discusses the public policy implications of HIV prevention coverage decisions, assesses possible legal grounds on which insurers may initially deny coverage for these technologies, and evaluates the extent to which these denials may survive external and judicial review. Because several of these legal grounds may be persuasive, particularly denials on the basis of medical necessity, this Article also explores alternative strategies for financing biomedical HIV prevention efforts. PMID:23356098
Ondondo, Beatrice O.
Development of an effective HIV/AIDS vaccine remains a big challenge, largely due to the enormous HIV diversity which propels immune escape. Thus novel vaccine strategies are targeting multiple variants of conserved antibody and T cell epitopic regions which would incur a huge fitness cost to the virus in the event of mutational escape. Besides immunogen design, the delivery modality is critical for vaccine potency and efficacy, and should be carefully selected in order to not only maximize transgene expression, but to also enhance the immuno-stimulatory potential to activate innate and adaptive immune systems. To date, five HIV vaccine candidates have been evaluated for efficacy and protection from acquisition was only achieved in a small proportion of vaccinees in the RV144 study which used a canarypox vector for delivery. Conversely, in the STEP study (HVTN 502) where human adenovirus serotype 5 (Ad5) was used, strong immune responses were induced but vaccination was more associated with increased risk of HIV acquisition than protection in vaccinees with pre-existing Ad5 immunity. The possibility that pre-existing immunity to a highly promising delivery vector may alter the natural course of HIV to increase acquisition risk is quite worrisome and a huge setback for HIV vaccine development. Thus, HIV vaccine development efforts are now geared toward delivery platforms which attain superior immunogenicity while concurrently limiting potential catastrophic effects likely to arise from pre-existing immunity or vector-related immuno-modulation. However, it still remains unclear whether it is poor immunogenicity of HIV antigens or substandard immunological potency of the safer delivery vectors that has limited the success of HIV vaccines. This article discusses some of the promising delivery vectors to be harnessed for improved HIV vaccine efficacy. PMID:25202303
... Resources Related Links Vaccines & Immunizations Mumps and the Vaccine (Shot) to Prevent It Language: English Español (Spanish) ... schedule. Fact Sheets for Parents Diseases and the Vaccines that Prevent Them Chickenpox Diphtheria Flu (Influenza) Hepatitis ...
... Resources Related Links Vaccines & Immunizations Polio and the Vaccine (Shot) to Prevent It Language: English Español (Spanish) ... schedule. Fact Sheets for Parents Diseases and the Vaccines that Prevent Them Chickenpox Diphtheria Flu (Influenza) Hepatitis ...
... PARENT S | DISEASES and the VACCINES THAT PREVENT THEM | Rotavirus and the Vaccine (Drops) to Prevent It Last ... February 2014 The best way to protect against rotavirus is by getting the rotavirus vaccine. Doctors recommend ...
Adamson, Blythe; Dimitrov, Dobromir; Devine, Beth; Barnabas, Ruanne
Objective The aim of this paper was to review and compare HIV vaccine cost-effectiveness analyses and describe the effects of uncertainty in model, methodology, and parameterization. Methods We systematically searched MEDLINE (1985 through May 2016), EMBASE, the Tufts CEA Registry, and reference lists of articles following Cochrane guidelines and PRISMA reporting. Eligibility criteria included peer-reviewed manuscripts with economic models estimating cost-effectiveness of preventative HIV vaccines. Two reviewers independently assessed study quality and extracted data on model assumptions, characteristics, input parameters, and outcomes. Results The search yielded 71 studies, of which 11 met criteria for inclusion. Populations included low-income (n=7), middle-income (n=4), and high-income countries (n=2). Model structure varied including decision tree (n=1), Markov (n=5), compartmental (n=4), and microsimulation (n=1). Most measured outcomes in quality adjusted life-years (QALYs) gained (n=6) while others used unadjusted (n=3) or disability adjusted life-years (n=2). HIV vaccine cost ranged from $1.54 -$75 USD in low-income countries, $55-$100 in middle-income countries, and $500-$1,000 in the United States. Base case ICERs ranged from dominant (cost-offsetting) to $91,000 per QALY gained. Conclusion Most models predicted HIV vaccines would be cost-effective. Model assumptions about vaccine price, HIV treatment costs, epidemic context, and willingness to pay influenced results more consistently than assumptions on HIV transmission dynamics. PMID:28367539
Kublin, James G; Morgan, Cecilia A; Day, Tracey A; Gilbert, Peter B; Self, Steve G; McElrath, M Juliana; Corey, Lawrence
The HIV Vaccine Trials Network (HVTN) is an international collaboration of scientists and educators facilitating the development of HIV/AIDS preventive vaccines. The HVTN conducts all phases of clinical trials, from evaluating experimental vaccines for safety and immunogenicity, to testing vaccine efficacy. Over the past decade, the HVTN has aimed to improve the process of designing, implementing and analyzing vaccine trials. Several major achievements include streamlining protocol development while maintaining input from diverse stakeholders, establishing a laboratory program with standardized assays and systems allowing for reliable immunogenicity assessments across trials, setting statistical standards for the field and actively engaging with site communities. These achievements have allowed the HVTN to conduct over 50 clinical trials and make numerous scientific contributions to the field. PMID:23243491
Castro, Jose G; Jones, Deborah L; Weiss, Stephen M
The objective of this pilot study was to explore the knowledge of and preferences regarding effective biomedical interventions among high risk individuals attending a sexually transmitted diseases clinic, and to examine the effect of a brief information intervention on preference. Participants completed a baseline assessment, attended a presentation on human immunodeficiency virus (HIV) prevention methods, and completed a postintervention assessment. Outcome measures included: demographics and sexual risk factors, self-perceived HIV risk, and knowledge and attitudes regarding new biomedical methods of HIV prevention. After the baseline evaluation, participants were provided with information on new biomedical prevention strategies. Participants were given the option to review the information by reading a pamphlet or by viewing a brief video containing the same information. Participants (n=97) were female (n=51) and male (n=46). At baseline, only a small minority of participants were aware of the newer biomedical strategies to prevent HIV infection. Postintervention, 40% endorsed having heard about the use of HIV medications to prevent HIV infection; 72% had heard that male circumcision can decrease the risk of acquiring HIV infection in men; and 73% endorsed knowledge of the potential role of microbicides in decreasing the risk of acquiring HIV. Following the intervention, the most preferred prevention method was male condoms, followed by preexposure prophylaxis, and microbicides. The least preferred methods were male circumcision and female condoms. This study provides preliminary information on knowledge and attitudes regarding newer biomedical interventions to protect against HIV infection. PMID:25540597
Expansion of HIV testing and ART treatment are core strategies for achieving the ambitious global goal of ending the HIV epidemic by the end of 2030, and achieving the "90-90-90" target by 2020. In China, great progress in HIV control and prevention has been made; however, there is room to enhance the effectiveness of HIV-related strategies. In addition, some implemented strategies have not achieved their expected output. To confront the challenge of sexual transmission of HIV, which is the main route of transmission in China, more targeted HIV prevention strategies that lead to their expected outcomes are essential. It is important to strengthen existing strategies that have been proved effective. However, it is also critical to create innovative strategies, and there are five approaches to achieve this. First, a holistic perspective should be adopted, to better understand the current situation and problems. This means intervention strategies should give serious consideration of how to meet the sociocultural needs of target populations rather than merely carry out behavioral interventions. Second, community-based HIV prevention settings should have more important roles in providing HIV-related health care services. Moreover, to improve the effectiveness of these strategies, a problem-led working style should be integrated into HIV prevention measures overall. Third, thoroughly analyzing characteristics of the current HIV epidemic using more evidence-based considerations must be undertaken, to better control HIV sexual transmission. Fourth, continued improvement of AIDS prevention and control mechanisms is needed, to ensure their sustainable development. Last, it is necessary to involve more NGOs in HIV prevention work by strengthening their management and working capacities to provide HIV-related services. Also needed is further improvement in both technical and management capacities, so as to build a stable basis for effective response.
Fraser, Clementine S; Jha, Akhilesh; Openshaw, Peter J M
Pneumonia is of great global public health importance. Viral infections play both direct and indirect parts in its cause across the globe. Influenza is a leading cause of viral pneumonia in both children and adults, and respiratory syncytial virus is increasingly recognized as causing disease at both extremes of age. Vaccination offers the best prospect for prevention but current influenza vaccines do not provide universal and durable protection, and require yearly reformulation. In the future, it is hoped that influenza vaccines will give better and universal protection, and that new vaccines can be found for other causes of viral pneumonia.
McElrath, M J; Hoffman, M; Kluckling, S; Corey, L; Greenberg, P D
The induction of CD8+ CTL responses is a goal of most HIV-1 vaccine trials, but such potentially protective effector responses have been difficult to evaluate, particularly in these vaccine prevention trials, due to technical obstacles. We report a method to evaluate CTL responses based on the ability to infect autologous macrophages with a monocytotropic strain of HIV-1, and to use these cells as efficient stimulators. This approach does not require the addition of exogenous cytokines, allows detection of class I-restricted CTLs against multiple HIV-1 gene products, and circumvents the problem, often detected using other stimulator cells, of high levels of lytic activity against target cells expressing vaccinia and/or EBV antigens. Adherent monocyte-derived macrophages were infected with HIV-1 Ba-L, and used within 2-3 weeks as autologous stimulators. Fresh PBMCs were cultured with the infected macrophages, harvested after 1 week, replated with fresh infected macrophages and filler cells, and tested after 5-7 days for cytolytic activity. CD8+ CTL responses specific for HIV-1 envelope were detected at an E:T ratio as low as 5:1 in two of four HIV-1-uninfected recipients of an HIV vaccine regimen that included a recombinant live vaccinia virus. Cytotoxic T lymphocyte activity could be detected > 1 year following vaccination. Similar lytic activity was detected with cryopreserved responder cells. In two HIV-1-infected individuals participating in a blinded therapeutic vaccination trial, the use of infected macrophages as in vitro stimulators permitted detection of the presence of envelope and gag-specific CTLs. No responses were observed in nonimmunized, uninfected controls. Thus, HIV-1-infected macrophages can stimulate in vitro the repertoire of primed HIV-reactive CD8+ precursors from seronegative and seropositive participants in HIV-1 vaccine trials, and should facilitate the identification of potentially effective candidate HIV vaccines.
Solomon, Isaac H; Milner, Danny A
The widespread use of vaccines has been one of the most important medical advances in the last century, saving trillions of dollars and millions of lives. Despite local eradication of some infections, travellers returning from affected areas may cause outbreaks through reintroduction of pathogens to individuals who are unable to receive vaccines for medical reasons or who have declined vaccination for non-medical reasons. Infections that would otherwise be uncommonly encountered by anatomical pathologists should therefore remain in the differential diagnosis for immunocompromised and unvaccinated patients. We review here the histopathological features and ancillary testing required for diagnosis of all illnesses preventable by vaccines that are currently approved for use by the United States Food and Drug Administration, organized into three sections: viral infections preventable by routine vaccination (measles, mumps, rubella, varicella, rotavirus, polio, hepatitis A, hepatitis B, influenza, and human papillomavirus), bacterial infections preventable by routine vaccination (diptheria, tetanus, pertussis, Haemophilus influenzae, pneumococcus, and meningococcus), and infections with specific vaccine indications (anthrax, typhoid, tuberculosis, rabies, Japanese encephalitis, yellow fever, smallpox, and adenovirus). Histopathology for the less common diseases is illustrated in this review. Awareness of a patient's immune and/or vaccine status is a crucial component of the infectious disease work-up, especially for rare diseases that may not otherwise be seen.
Liu, Ye; Balachandran, Yekkuni L; Li, Dan; Shao, Yiming; Jiang, Xingyu
One of the biggest obstacles for the development of HIV vaccines is how to sufficiently trigger crucial anti-HIV immunities via a safe manner. We herein integrated surface modification-dependent immunostimulation against HIV vaccine and shape-dependent biosafety and designed a safe noncarrier adjuvant based on silver nanorods coated by both polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG). Such silver nanorods can significantly elevate crucial immunities of HIV vaccine and overcome the toxicity, which is a big problem for other existing adjuvants. This study thus provided a principle for designing a safe and high-efficacy material for an adjuvant and allow researchers to really have a safe and effective prophylaxis against HIV. We expect this material approach to be applicable to other types of vaccines, whether they are preventative or therapeutic.
Des Jarlais, D C; Padian, N
The controversy over "targeted" versus "universalistic" programs for HIV prevention has persisted throughout the history of the HIV/AIDS epidemic in the United States and in some European countries. Building on previous analyses, we outline methods for integrating universalistic and targeted HIV prevention programming. The outline considers possible synergy between targeted and universalistic programs, rather than a forced choice between the two. Components within this framework include a continuum of the intensity of targeted programs, specification of local risk behavior populations, categories of risk behavior, and HIV seroprevalence within local risk-behavior populations. Given the scarce resources currently available, preventing all new HIV infections is not a realistic public health goal, but with better use of current scientific knowledge, it should be possible to greatly reduce the rate of new HIV infections.
The development of an effective HIV vaccine has been an ongoing area of research. The high variability in HIV-1 virus strains has represented a major challenge in successful development. Ideally, an effective candidate vaccine would provide protection against the majority of clades of HIV. Two major hurdles to overcome are immunodominance and sequence diversity. This vaccine utilizes a strategy for overcoming these two issues by identifying the conserved regions of the virus and exploiting them for use in a targeted therapy. NCI seeks licensees and/or research collaborators to commercialize this technology, which has been validated in macaque models.
Madhi, Shabir A.; Koen, Anthonet; Jose, Lisa; van Niekerk, Nadia; Adrian, Peter V.; Cutland, Clare; François, Nancy; Ruiz-Guiñazú, Javier; Yarzabal, Juan-Pablo; Moreira, Marta; Borys, Dorota; Schuerman, Lode
Abstract Background: Phase III, open-label, single-center, controlled study in South Africa (ClinicalTrials.gov: NCT00829010) to evaluate immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in human immunodeficiency virus (HIV)-infected (HIV+), HIV-exposed-uninfected (HEU), and HIV-unexposed-uninfected (HUU) children. Methods: Children stratified by HIV status received PHiD-CV primary vaccination (age 6/10/14 weeks; coadministered with routine childhood vaccines) and booster dose (age 9–10 months). Immune responses, assessed using enzyme-linked immunosorbent and functional assays, and safety were evaluated up to 14 months post-booster. Results: Of 83, 101, and 100 children enrolled in HIV+, HEU, and HUU groups, 70, 91, and 93 were included in according-to-protocol immunogenicity cohort. For each vaccine-serotype, percentages of children with antibody concentrations ≥0.2 μg/mL were ≥97% 1 month post-primary vaccination and ≥98.5% 1 month post-booster (except for 6B and 23F at both timepoints). Post-primary vaccination, functional antibody responses were lower in HIV+ children: for each vaccine-serotype, percentages of children with opsonophagocytic activity (OPA) titres ≥8 were ≥72%, ≥81%, and ≥79% for HIV+, HEU, and HUU children. Post-booster, ≥87% of children in each group had OPA titres ≥8. Reactogenicity was similar across groups. Thirty one (37%) HIV+, 25 (25%) HEU, and 20 (20%) HUU children reported ≥1 serious adverse event. Five HIV+ and 4 HEU children died. One death (sudden infant death syndrome; HEU group; 3 days post-dose 1) was considered potentially vaccine-related. Conclusion: PHiD-CV was immunogenic and well-tolerated in HIV+, HEU, and HUU children, and has the potential to provide substantial benefit irrespective of HIV infection status. PMID:28079828
Avelino-Silva, Vivian Iida; Francelino, Hilario Sousa; Kallás, Esper Georges
Introduction: Vaccination is the main preventive strategy against Yellow Fever (YF), which is a public health concern in Brazil. However, HIV-infected patients might have insufficient knowledge regarding YF, YF prevention, and vaccines in general. Methods: In this questionnaire-based study, data from 158 HIV-infected individuals were addressed in three distinct outpatient clinics in São Paulo. Information was collected on demographic and clinical characteristics, as well as patients' knowledge of vaccines, YF and YF preventive strategies. In addition, individual YF vaccine recommendations and vaccine status were investigated. Results: Although most participants adequately ascertain the vaccine as the main prevention strategy against YF, few participants were aware of the severity and lack of specific treatment for YF. Discrepancy in YF vaccine (patients who should have taken the vaccine, but did not) was observed in 18.8% of participants. Conclusion: YF is an important and preventable public health concern, and these results demonstrate that more information is necessary for the HIV-infected population. PMID:25229222
The Centers for Disease Control and Prevention (CDC) Sexually Transmitted Disease (STD) Treatment Guidelines were last updated in 2006. To update the “Clinical Guide to Prevention Services” section of the 2010 CDC STD Treatment Guidelines, we reviewed the recent science with reference to interventions designed to prevent acquisition of STDs, including human immunodeficiency virus (HIV) infection. Major interval developments include (1) licensure and uptake of immunization against genital human papillomavirus, (2) validation of male circumcision as a potent prevention tool against acquisition of HIV and some other sexually transmitted infections (STIs), (3) failure of a promising HIV vaccine candidate to afford protection against HIV acquisition, (4) encouragement about the use of antiretroviral agents as preexposure prophylaxis to reduce risk of HIV and herpes simplex virus acquisition, (5) enhanced emphasis on expedited partner management and rescreening for persons infected with Chlamydia trachomatis and Neisseria gonorrhoeae, (6) recognition that behavioral interventions will be needed to address a new trend of sexually transmitted hepatitis C among men who have sex with men, and (7) the availability of a modified female condom. A range of preventive interventions is needed to reduce the risks of acquiring STI, including HIV infection, among sexually active people, and a flexible approach targeted to specific populations should integrate combinations of biomedical, behavioral, and structural interventions. These would ideally involve an array of prevention contexts, including (1) communications and practices among sexual partners, (2) transactions between individual clients and their healthcare providers, and (3) comprehensive population-level strategies for prioritizing prevention research, ensuring accurate outcome assessment, and formulating health policy. PMID:22080271
Goncalves, Priscila H.; Montezuma-Rusca, Jairo M.; Yarchoan, Robert; Uldrick, Thomas S.
People living with human immunodeficiency virus (HIV) are living longer since the advent of effective combined antiretroviral therapy (cART). While cART substantially decreases the risk of developing some cancers, HIV-infected individuals remain at high risk for Kaposi sarcoma, lymphoma and several solid tumors. Currently HIV-infected patients represent an aging group, and malignancies have become a leading cause of morbidity and mortality. Tailored cancer-prevention strategies are needed for this population. In this review we describe the etiologic agents and pathogenesis of common malignancies in the setting of HIV, as well as current evidence for cancer prevention strategies and screening programs. PMID:26970136
Eriksson, Klara K.; Makia, Divine; Maier, Reinhard; Ludewig, Burkhard; Thiel, Volker
Human immunodeficiency virus (HIV) infection represents one of the major health threats in the developing world. The costly treatment of infected individuals with multiple highly efficient anti-HIV drugs is only affordable in industrialized countries. Thus, an efficient vaccination strategy is required to prevent the further spread of the infection. The molecular biology of coronaviruses and particular features of the human coronavirus 229E (HCoV 229E) indicate that HCoV 229E-based vaccine vectors can become a new class of highly efficient vaccines. First, the receptor of HCoV 229E, human aminopeptidase N (hAPN or CD13) is expressed mainly on human dendritic cells (DCs) and macrophages indicating that targeting of HCoV 229E-based vectors to professional antigen presenting cells can be achieved by receptor-mediated transduction. Second, HCoV 229E structural genes can be replaced by multiple transcriptional units encoding various antigens. These virus-like particles (VLPs) containing HCoV 229E-based vector RNA have the ability to transduce human DCs and to mediate heterologous gene expression in these cells. Finally, coronavirus infections are associated with mainly respiratory and enteric diseases, and natural transmission of coronaviruses occurs via mucosal surfaces. In humans, HCoV 229E causes common cold by infecting the upper respiratory tract. HCoV 229E infections are mainly encountered in children and re-infection occurs frequently in adults. It is thus most likely that pre-existing immunity against HCoV 229E will not significantly impact on the vaccination efficiency if HCoV 229E-based vectors are used in humans. PMID:17162377
Lightfoot, Marguerita; Rotheram-Borus, Mary Jane; Tevendale, Heather
As the number of youth infected with HIV rises, secondary prevention programs are needed to help youth living with HIV meet three goals: (1) increase self-care behaviors, medical adherence, and health-related interactions; (2) reduce transmission acts; and (3) enhance their quality of life. This article describes an intervention program for youth…
Cottrell, Mackenzie L; Kashuba, Angela D. M.
Worldwide, HIV disproportionately affects women who are often unable to negotiate traditional HIV preventive strategies such as condoms. In the absence of an effective vaccine or cure, chemoprophylaxis may be a valuable self-initiated alternative. Topical microbicides have been investigated as one such option. The first generation topical microbicides were non-specific, broad-spectrum antimicrobial agents, including surfactants, polyanions, and acid buffering gels, that generally exhibited contraceptive properties. After extensive clinical study, none prevented HIV infection, and their development was abandoned. Second generation topical microbicides include agents with selective mechanisms of antiviral activity. Most are currently being used for, or have previously been explored as, drugs for treatment of HIV. The most advanced of these is tenofovir 1% gel: the first topical agent shown to significantly reduce HIV infection by 39% compared to placebo. This review summarizes the evolution of topical microbicides for HIV chemoprophylaxis, highlights important concepts learned, and offers current and future considerations for this area of research. PMID:24664786
Liu, Yang; Liu, Jianying; Cheng, Gong
Dengue is currently the most significant arboviral disease afflicting tropical and sub-tropical countries worldwide. Dengue vaccines, such as the multivalent attenuated, chimeric, DNA and inactivated vaccines, have been developed to prevent dengue infection in humans, and they function predominantly by stimulating immune responses against the dengue virus (DENV) envelope (E) and nonstructural-1 proteins (NS1). Of these vaccines, a live attenuated chimeric tetravalent DENV vaccine developed by Sanofi Pasteur has been licensed in several countries. However, this vaccine renders only partial protection against the DENV2 infection and is associated with an unexplained increased incidence of hospitalization for severe dengue disease among children younger than nine years old. In addition to the virus-based vaccines, several mosquito-based dengue immunization strategies have been developed to interrupt the vector competence and effectively reduce the number of infected mosquito vectors, thus controlling the transmission of DENV in nature. Here we summarize the recent progress in the development of dengue vaccines and novel immunization strategies and propose some prospective vaccine strategies for disease prevention in the future. PMID:27436365
Liu, Yang; Liu, Jianying; Cheng, Gong
Dengue is currently the most significant arboviral disease afflicting tropical and sub-tropical countries worldwide. Dengue vaccines, such as the multivalent attenuated, chimeric, DNA and inactivated vaccines, have been developed to prevent dengue infection in humans, and they function predominantly by stimulating immune responses against the dengue virus (DENV) envelope (E) and nonstructural-1 proteins (NS1). Of these vaccines, a live attenuated chimeric tetravalent DENV vaccine developed by Sanofi Pasteur has been licensed in several countries. However, this vaccine renders only partial protection against the DENV2 infection and is associated with an unexplained increased incidence of hospitalization for severe dengue disease among children younger than nine years old. In addition to the virus-based vaccines, several mosquito-based dengue immunization strategies have been developed to interrupt the vector competence and effectively reduce the number of infected mosquito vectors, thus controlling the transmission of DENV in nature. Here we summarize the recent progress in the development of dengue vaccines and novel immunization strategies and propose some prospective vaccine strategies for disease prevention in the future.
Apart from live spore vaccines with a certain amount of residual virulence for various animal species, there are two acellular protein vaccines for immunoprophylaxis against anthrax in humans. For ethical reasons there are no experimental data available on the efficacy and duration of the immunity they induce in men. Their efficacy was evaluated in laboratory animals, mainly rabbits and rhesus monkeys. Furthermore, it is well known that these vaccines elicit only partial protection in guinea pigs and almost no protection in mice against a challenge with fully virulent spores of Bacillus (B.) anthracis. Other disadvantages are the high amount of boosters necessary to elicit and to maintain a protective immune response, the variability in the composition of bacterial culture supernatants used for production, and the appearance of clinically relevant side effects. Therefore, there is ongoing work worldwide to improve the existing vaccines by substitution with recombinant antigens and to develop new vaccines on the basis of recombinant bacterial or viral live vectors, DNA-vectors, and by addition of new adjuvants. Special attention is given to supplementing the existing toxoid-vaccines with an anti-bacterial component.
Hicar, Mark D
Although pharmacological interventions have been successful in reducing prevention of maternal to child transmission (PMTCT) of HIV, there is concern that complete elimination through this mode of transmission will require other measures. Immunotherapies in infants or pregnant mothers may be able to eradicate this form of transmission. A recent vaccine trial in adults showed encouraging results, but as in most HIV safety and efficacy vaccine trials, the question of MTCT was not addressed. Concentrating transmission studies and vaccine studies in the setting of MTCT offers several advantages. MTCT has a generally reproducible known transmission rate and has been successfully used to assess pharmacological interventions on decreasing transmission. Even in resource poor settings, the infrastructure for neonatal vaccination is already in place. Although rare, both passive and active vaccination trials have been successfully completed in pediatric populations. Unfortunately, little success in affecting MTCT has been shown. Largely, a correlate of protection in any type of transmission, including MTCT, is unknown. Data supports a role for antibodies in effecting strain and transmission during MTCT. The role of antibodies in MTCT is reviewed with a focus on recent passive immunization and considerations for future studies.
Stoliaroff-Pépin, Anna; Speck, Roberto F; Vernazza, Pietro
The number of new HIV-1 infections remains stable in Switzerland over the last years thanks to the effective prevention programs. However, the aim to halve the new HIV infection rate has not been reached. Early identification of patients at risk of acquiring HIV infection and counselling "safer sex" rules as well as treating HIV-infected patients plays a decisive role in this program. Studies are -ongoing to investigate additional preventive measures such as pre-exposure prophylaxis, microbicides and vaccines, but none of those approaches permit omitting "safer sex". Incidences of other sexual transmitted infections are increasing rapidly, in particular the incidence of Syphilis. Transmission occurs more often orally or rectally than vaginally and patients are often asymptomatic. Condoms provide only limited protection. In addition antibiotic resistance emerges complicating the therapy, as for example for gonorrhea. Testing and treatment of infected patients is primordial as well as contact tracing. In this work, we discuss the different elements for preventing STIs with major emphasis on HIV.
Chiao, Chi; Mishra, Vinod; Ksobiech, Kate
High HIV rates among cohabiting couples in many African countries have led to greater programmatic emphasis on spousal communication in HIV prevention. This study examines how demographic and socioeconomic characteristics of cohabiting adults influence their dyadic communication about HIV. A central focus of this research is on how the position of women relative to their male partners influences spousal communication about HIV prevention. The authors analyze gaps in spousal age and education and females' participation in household decision making as key factors influencing spousal communication about HIV, while controlling for sexual behaviors of both partners as well as other individual and contextual factors. Data were obtained from the 2003 Kenya Demographic and Health Survey for 1,388 cohabiting couples. Information regarding spousal communication was self-reported, assessing whether both, either, or neither partner ever discussed HIV prevention with the other. Analyses showed higher levels of education for the female partner and participation in household decision making are positively associated with spousal communication about HIV prevention. With females' education and other factors controlled, couples with more educated male partners were more likely to have discussed HIV prevention than couples in which both partners have the same level of education. Spousal communication was also positively associated with household wealth status and exposure to the mass media, but couples in which male partners reported having nonspousal sex in the past year were less likely to have discussed HIV prevention with their spouses. Findings suggest HIV prevention programs should promote female empowerment and encourage male participation in sexual health discussion.
Vzorov, A N; Compans, R W
An ideal protective HIV-1 vaccine can elicit broadly neutralizing antibodies, capable of preventing HIV transmission. The strategies of designing vaccines include generation of soluble recombinant proteins which mimic the native Env complex and are able to enhance the immunogenicity of gp120. Recent data indicate that the cytoplasmic tail (CT) of the Env protein has multiple functions, which can affect the early steps of infection, as well as viral assembly and antigenic properties. Modifications in the CT can be used to induce conformational changes in functional regions of gp120 and to stabilize the trimeric structure, avoiding immune misdirection and induction of non-neutralizing antibody responses. Env-trimers with modified CTs in virus-like particles (VLPs) are able to induce antibodies with broad spectrum neutralizing activity and high avidity and have the potential for developing an effective vaccine against HIV.
Horiya, Satoru; MacPherson, Iain S.; Krauss, Isaac J.
Although efforts to develop a vaccine against HIV have so far met with little success, recent studies of HIV-positive patients with strongly neutralizing sera have shown that the human immune system is capable of producing potent and broadly-neutralizing antibodies (bnAbs), some of which neutralize up to 90 % of HIV strains. These antibodies bind to conserved vulnerable sites on the viral envelope glycoprotein gp120, and identification of these sites has provided tantalizing clues about the design of potentially effective vaccines. Carbohydrates play a key role in this field, as a large fraction of bnAbs bind to carbohydrates or combinations of carbohydrate and peptide elements on gp120. Additionally, carbohydrates partially mask some peptide surfaces recognized by bnAbs. The use of engineered glycoproteins and other glycostructures as vaccines to elicit antibodies with broad neutralizing activity is therefore a key area of interest in HIV vaccine design. PMID:25393493
Williams, Wilton B; Liao, Hua-Xin; Moody, M Anthony; Kepler, Thomas B; Alam, S Munir; Gao, Feng; Wiehe, Kevin; Trama, Ashley M; Jones, Kathryn; Zhang, Ruijun; Song, Hongshuo; Marshall, Dawn J; Whitesides, John F; Sawatzki, Kaitlin; Hua, Axin; Liu, Pinghuang; Tay, Matthew Z; Seaton, Kelly E; Shen, Xiaoying; Foulger, Andrew; Lloyd, Krissey E; Parks, Robert; Pollara, Justin; Ferrari, Guido; Yu, Jae-Sung; Vandergrift, Nathan; Montefiori, David C; Sobieszczyk, Magdalena E; Hammer, Scott; Karuna, Shelly; Gilbert, Peter; Grove, Doug; Grunenberg, Nicole; McElrath, M Juliana; Mascola, John R; Koup, Richard A; Corey, Lawrence; Nabel, Gary J; Morgan, Cecilia; Churchyard, Gavin; Maenza, Janine; Keefer, Michael; Graham, Barney S; Baden, Lindsey R; Tomaras, Georgia D; Haynes, Barton F
An HIV-1 DNA prime vaccine, with a recombinant adenovirus type 5 (rAd5) boost, failed to protect from HIV-1 acquisition. We studied the nature of the vaccine-induced antibody (Ab) response to HIV-1 envelope (Env). HIV-1-reactive plasma Ab titers were higher to Env gp41 than to gp120, and repertoire analysis demonstrated that 93% of HIV-1-reactive Abs from memory B cells responded to Env gp41. Vaccine-induced gp41-reactive monoclonal antibodies were non-neutralizing and frequently polyreactive with host and environmental antigens, including intestinal microbiota (IM). Next-generation sequencing of an immunoglobulin heavy chain variable region repertoire before vaccination revealed an Env-IM cross-reactive Ab that was clonally related to a subsequent vaccine-induced gp41-reactive Ab. Thus, HIV-1 Env DNA-rAd5 vaccine induced a dominant IM-polyreactive, non-neutralizing gp41-reactive Ab repertoire response that was associated with no vaccine efficacy.
Cagigi, Alberto; Cotugno, Nicola; Giaquinto, Carlo; Nicolosi, Luciana; Bernardi, Stefania; Rossi, Paolo; Douagi, Iyadh; Palma, Paolo
Current evidence on routine immunization of HIV-1 infected children point out the need for a special vaccine schedule in this population. However, optimal strategies for identifying individuals susceptible to infections, and then offering them sustained protection through appropriate immunization schedule, both in terms of timing and number of vaccine doses, still remain to be elucidated. Understanding the degree of immune recovery after HAART initiation is important in guiding administration of routine vaccination in HIV-1 infected children. Although quantitative measures (e.g., CD4+ T-cell counts and immunoglobulin levels) are frequently performed to evaluate immune parameters, these measures do not fully mirror functional immune recovery. Here, we will review the status of single mandatory and recommended vaccines for HIV-1 infected children in relation to immune recovery after HAART initiation with the aim of identifying new means to help design personalized vaccine schedules for this population. PMID:22906931
Journal of School Health, 1994
Examines issues in preventing further Human Immunodeficiency Virus (HIV) infection among adolescents, highlighting HIV and other sexually transmitted diseases, substance use, adolescent development, cultural and language diversity, health and social service needs, socioeconomic contexts, and role of media, school, and youth-serving organizations.…
Reducing the incidence of HIV infection continues to be a crucial public health priority in the United States, especially among populations at elevated risk such as men who have sex with men, transgender women, people who inject drugs, and racial and ethnic minority communities. Although most HIV prevention efforts to date have focused on changing risky behaviors, the past decade yielded efficacious new biomedical technologies designed to prevent infection, such as the prophylactic use of antiretroviral drugs and the first indications of an efficacious vaccine. Access to prevention technologies will be a significant part of the next decade's response to HIV and advocates are mobilizing to achieve more widespread use of these interventions. These breakthroughs, however, arrive at a time of escalating healthcare costs; health insurance coverage therefore raises pressing new questions about priority-setting and the allocation of responsibility for public health. The goals of this Article are to identify legal challenges and potential solutions for expanding access to biomedical HIV prevention through health insurance coverage. This Article discusses the public policy implications of HIVprevention coverage decisions, assesses possible legal grounds on which insurers may initially deny coverage for these technologies, and evaluates the extent to which these denials may survive external and judicial review. Because several of these legal grounds may be persuasive, particularly denials on the basis of medical necessity, this Article also explores alternative strategies for financing biomedical HIV prevention efforts.
Kim, Jerome H.; Rerks-Ngarm, Supachai; Excler, Jean-Louis; Michael, Nelson L.
Purpose of Review An effective HIV vaccine is a global health priority. We describe lessons learned from four HIV vaccine trials that failed to demonstrate efficacy and one that showed modest protection as a pathway forward. Recent findings The Merck Ad5 phase IIb T-cell vaccine failed to show efficacy and might have increased the risk of HIV acquisition in MSM. While VaxGen gp120 alone was not efficacious in groups at high risk for HIV-1 infection, the RV144 ALVAC prime and gp120 boost regimen showed 31% efficacy in low incidence heterosexuals. All trials demonstrated the limitations of available laboratory and animal models to both assess relevant vaccine-induced immune responses and to predict clinical trial outcome. Analysis of innate and adaptive responses induced in RV 144 will guide future trial design. Summary Future HIV vaccine trials should define the RV 144 immune responses relevant to protection, improve durability and level of protection, and assess efficacy in diverse risk groups. New strategies examining heterologous vector prime boost, universal inserts, replicating vectors, and novel protein/adjuvant immunogens should be explored to induce both T-cell and antibody responses. HIV vaccine development requires innovative ideas and a sustained long-term commitment of scientists, governments, and the community. PMID:20978385
Smed-Sörensen, Anna; Loré, Karin
As dendritic cells (DCs) have the unique capacity to activate antigen-naive T cells they likely play a critical role in eliciting immune responses to vaccines. DCs are therefore being explored as attractive targets for vaccines, but understanding the interaction of DCs and clinically relevant vaccine antigens and adjuvants is a prerequisite. The HIV-1/AIDS epidemic continues to be a significant health problem, and despite intense research efforts over the past 30 years a protective vaccine has not yet been developed. A common challenge in vaccine design is to find a vaccine formulation that best shapes the immune response to protect against and/or control the given pathogen. Here, we discuss the importance of understanding the diversity, anatomical location and function of different human DC subsets in order to identify the optimal target cells for an HIV-1 vaccine. We review human DC interactions with some of the HIV-1 vaccine antigen delivery vehicles and adjuvants currently utilized in preclinical and clinical studies. Specifically, the effects of distinctly different vaccine adjuvants in terms of activation of DCs and improving DC function and vaccine efficacy are discussed. The susceptibility and responses of DCs to recombinant adenovirus vectors are reviewed, as well as the strategy of directly targeting DCs by using DC marker-specific monoclonal antibodies coupled to an antigen.
Huang, Ying; Gilbert, Peter B; Fu, Rong; Janes, Holly
SummaryBiomarker endpoints measuring vaccine-induced immune responses are essential to HIV vaccine development because of their potential to predict the effect of a vaccine in preventing HIV infection. A vaccine's immune response profile observed in phase I immunogenicity studies is a key factor in determining whether it is advanced for further study in phase II and III efficacy trials. The multiplicity of immune variables and scientific uncertainty in their relative importance, however, pose great challenges to the development of formal algorithms for selecting vaccines to study further. Motivated by the practical need to identify a set of promising vaccines from a pool of candidate regimens for inclusion in an upcoming HIV vaccine efficacy trial, we propose a new statistical framework for the selection of vaccine regimens based on their immune response profile. In particular, we propose superiority and non-redundancy criteria to be achieved in down-selection, and develop novel statistical algorithms that integrate hypothesis testing and ranking for selecting vaccine regimens satisfying these criteria. Performance of the proposed selection algorithms are evaluated through extensive numerical studies. We demonstrate the application of the proposed methods through the comparison of immune responses between several HIV vaccine regimens. The methods are applicable to general down-selection applications in clinical trials.
Rotheram-Borus, Mary Jane; Swendeman, Dallas; Chovnick, Gary
In the past 25 years, the field of HIV prevention research has been transformed repeatedly. Today, effective HIV prevention requires a combination of behavioral, biomedical, and structural intervention strategies. Risk of transmitting or acquiring HIV is reduced by consistent male and female-condom use, reductions in concurrent and/or sequential sexual and needle-sharing partners, male circumcision, and treatment with antiretroviral medications. At least 144 behavioral prevention programs have been found effective in reducing HIV transmission acts; however, scale up of these programs has not occurred outside of the United States. A series of recent failures of HIV-prevention efficacy trials for biomedical innovations such as HIV vaccines, treating herpes simplex 2 and other sexually transmitted infections, and diaphragm and microbicide barriers highlights the need for behavioral strategies to accompany biomedical strategies. This challenges prevention researchers to reconceptualize how cost-effective, useful, realistic, and sustainable prevention programs will be designed, delivered, tested, and diffused. The next generation of HIV prevention science must draw from the successes of existing evidence-based interventions and the expertise of the market sector to integrate preventive innovations and behaviors into everyday routines. PMID:19327028
Etcheverry, M Florencia; Lum, Paula J; Evans, Jennifer L; Sanchez, Emilia; de Lazzari, Elisa; Mendez-Arancibia, Eva; Sierra, Ernesto; Gatell, José M; Page, Kimberly; Joseph, Joan
Being able to recruit high-risk volunteers who are also willing to consider future participation in vaccine trials are critical features of vaccine preparedness studies. We described data from two cohorts of injection- and non-injection drug users in Barcelona, Spain [Red Cross centre] and in San Francisco, USA, [UFO-VAX study] at high risk of HIV/HCV infection to assess behaviour risk exposure and willingness to participate in future preventive HIV vaccine trials. We successfully identified drug-using populations that would be eligible for future HIV vaccine efficacy trials, based on reported levels of risk during screening and high levels of willingness to participate. In both groups, Red Cross and UFO-VAX respectively, HCV infection was highly prevalent at baseline (41% and 34%), HIV baseline seroprevalence was 4.2% and 1.5%, and high levels of willingness were seen (83% and 78%).
Etcheverry, M. Florencia; Lum, Paula J.; Evans, Jennifer L.; Sanchez, Emilia; de Lazzari, Elisa; Mendez-Arancibia, Eva; Sierra, Ernesto; Gatell, José M.; Page, Kimberly; Joseph, Joan
Being able to recruit high-risk volunteers who are also willing to consider future participation in vaccine trials are critical features of vaccine preparedness studies. We described data from two cohorts of injection- and non-injection drug users in Barcelona, Spain [Red Cross centre] and in San Francisco, USA, [UFO-VAX study] at high risk of HIV/HCV infection to assess behaviour risk exposure and willingness to participate in future preventive HIV vaccine trials. We successfully identified drug-using populations that would be eligible for future HIV vaccine efficacy trials, based on reported levels of risk during screening and high levels of willingness to participate. In both groups, Red Cross and UFO-VAX respectively, HCV infection was highly prevalent at baseline (41% and 34%), HIV baseline seroprevalence was 4.2% and 1.5%, and high levels of willingness were seen (83% and 78%). PMID:21241735
Fernando, Kathy; Hu, Haitao; Ni, Houping; Hoxie, James A.
The human immunodeficiency virus (HIV) causes impairment of the immune system in part by targeting CD4+ T cells for infection and dysfunction. HIV envelope (Env) present on free virions and infected cells causes dysfunction of uninfected bystander CD4+ T cells via interaction with both CD4 and coreceptors. Env is commonly used as part of a cocktail of HIV antigens in current vaccines. In DNA and viral vector vaccine approaches, antigen-presenting cells (APCs) and non-APCs in the vicinity of the vaccine delivery site and draining lymph node express vaccine-derived antigens. The studies here demonstrate that cell-surface expression of Env on APCs and non-APCs as part of the vaccine action causes an inhibition of antigen-induced CD4+ T-cell activation and proliferation mediated by CD4 binding and suggests a potential mechanism for reduced activity of Env-containing HIV vaccines. Similar studies using a functional Env lacking CD4 binding circumvented suppression, suggesting an alternative and potentially superior approach to HIV vaccine design. PMID:17158230
Gasper, Melanie A.; Hesseling, Anneke C.; Mohar, Isaac; Myer, Landon; Azenkot, Tali; Passmore, Jo-Ann S.; Hanekom, Willem; Cotton, Mark F.; Crispe, I. Nicholas; Sodora, Donald L.; Jaspan, Heather B.
BACKGROUND. Bacillus Calmette-Guérin (BCG) vaccine is administered at birth to protect infants against tuberculosis throughout Africa, where most perinatal HIV-1 transmission occurs. We examined whether BCG vaccination alters the levels of activated HIV target T cells in HIV-exposed South African infants. METHODS. HIV-exposed infants were randomized to receive routine (at birth) or delayed (at 8 weeks) BCG vaccination. Activated and CCR5-expressing peripheral blood CD4+ T cell, monocyte, and NK cell frequencies were evaluated by flow cytometry and immune gene expression via PCR using Biomark (Fluidigm). RESULTS. Of 149 infants randomized, 92% (n = 137) were retained at 6 weeks: 71 in the routine BCG arm and 66 in the delayed arm. Routine BCG vaccination led to a 3-fold increase in systemic activation of HIV target CD4+CCR5+ T cells (HLA-DR+CD38+) at 6 weeks (0.25% at birth versus 0.08% in delayed vaccination groups; P = 0.029), which persisted until 8 weeks of age when the delayed arm was vaccinated. Vaccination of the infants in the delayed arm at 8 weeks resulted in a similar increase in activated CD4+CCR5+ T cells. The increase in activated T cells was associated with increased levels of MHC class II transactivator (CIITA), IL12RB1, and IFN-α1 transcripts within peripheral blood mononuclear cells but minimal changes in innate cells. CONCLUSION. BCG vaccination induces immune changes in HIV-exposed infants, including an increase in the proportion of activated CCR5+CD4+ HIV target cells. These findings provide insight into optimal BCG vaccine timing to minimize the risks of HIV transmissions to exposed infants while preserving potential benefits conferred by BCG vaccination. TRIAL REGISTRATION. ClinicalTrials.gov NCT02062580. FUNDING. This trial was sponsored by the Elizabeth Glaser Pediatric AIDS Foundation (MV-00-9-900-01871-0-00) and the Thrasher Foundation (NR-0095); for details, see Acknowledgments.
Wu, Jashin J; Huang, David B; Pang, Katie R; Tyring, Stephen K
Although the development of antimicrobial drugs has advanced rapidly in the past several years, such agents act against only certain groups of microbes and are associated with increasing rates of resistance. These limitations of treatment force physicians to continue to rely on prevention, which is more effective and cost-effective than therapy. From the use of the smallpox vaccine by Jenner in the 1700s to the current concerns about biologic warfare, the technology for vaccine development has seen numerous advances. The currently available vaccines for viral illnesses include Dryvax for smallpox; the combination measles, mumps, and rubella vaccine; inactivated vaccine for hepatitis A; plasma-derived vaccine for hepatitis B; and the live attenuated Oka strain vaccine for varicella zoster. Vaccines available against bacterial illnesses include those for anthrax, Haemophilus influenzae, and Neisseria meningitidis. Currently in development for both prophylactic and therapeutic purposes are vaccines for HIV, herpes simplex virus, and human papillomavirus. Other vaccines being investigated for prevention are those for cytomegalovirus, respiratory syncytial virus, parainfluenza virus, hepatitis C, and dengue fever, among many others. Fungal and protozoan diseases are also subjects of vaccine research. Among immunoglobulins approved for prophylactic and therapeutic use are those against cytomegalovirus, hepatitis A and B, measles, rabies, and tetanus. With this progress, it is hoped that effective vaccines soon will be developed for many more infectious diseases with cutaneous manifestations.
Flood, Danna; Wallace, Melissa; Bloch, Kimberly; Kublin, James; Bekker, Linda-Gail
Background HIV remains a significant health problem in South Africa (SA). The development of a preventive vaccine offers promise as a means of addressing the epidemic, yet development of the human resource capacity to facilitate such research in SA is not being sustained. The HIV Vaccine Trials Network (HVTN) has responded by establishing South African/HVTN AIDS Early Stage Investigator Programme (SHAPe), a programme to identify, train and retain clinician scientists in HIV vaccine research in SA. Objectives The present study sought to identify factors influencing the attraction and retention of South African medical doctors in HIV vaccine research; to understand the support needed to ensure their success; and to inform further development of clinician research programmes, including SHAPe. Methods Individual interviews and focus groups were held and audio-recorded with 18 senior and junior research investigators, and medical doctors not involved in research. Recordings were transcribed, and data were coded and analysed. Results Findings highlighted the need for: (1) medical training programmes to include a greater focus on fostering interest and developing research skills, (2) a more clearly defined career pathway for individuals interested in clinical research, (3) an increase in programmes that coordinate and fund research, training and mentorship opportunities and (4) access to academic resources such as courses and libraries. Unstable funding sources and inadequate local funding support were identified as barriers to promoting HIV research careers. Conclusion Expanding programmes that provide young investigators with funded research opportunities, mentoring, targeted training and professional development may help to build and sustain SA’s next generation of HIV vaccine and prevention scientists. PMID:27616977
García, Felipe; Plana, Montserrat; Climent, Nuria; León, Agathe; Gatell, Jose M; Gallart, Teresa
Dendritic cells have a central role in HIV infection. On one hand, they are essential to induce strong HIV-specific CD4⁺ helper T-cell responses that are crucial to achieve a sustained and effective HIV-specific CD8⁺ cytotoxic T-lymphocyte able to control HIV replication. On the other hand, DCs contribute to virus dissemination and HIV itself could avoid a correct antigen presentation. As the efficacy of immune therapy and therapeutic vaccines against HIV infection has been modest in the best of cases, it has been hypothesized that ex vivo generated DC therapeutic vaccines aimed to induce effective specific HIV immune responses might overcome some of these problems. In fact, DC-based vaccine clinical trials have yielded the best results in this field. However, despite these encouraging results, functional cure has not been reached with this strategy in any patient. In this Commentary, we discuss new approaches to improve the efficacy and feasibility of this type of therapeutic vaccine.
Nutan; Gupta, Satish K.
Human immunodeficiency virus (HIV), causative agent of acquired immunodeficiency syndrome (AIDS), is a global health concern. To control its transmission, safe sex has been proposed as one of the strategies. Microbicides- intravaginal/intrarectal topical formulations of anti-HIV agents have also been proposed to prevent HIV transmission. Microbicides would provide protection by directly inactivating HIV or preventing the attachment, entry or replication of HIV in susceptible target cells as well as their dissemination from target cells present in semen or the host cells lining the vaginal/rectal wall to other migratory cells. Microbicides must be safe, effective following vaginal or rectal administration, and should cause minimal or no genital symptoms or inflammations following long-term repeated usage. However, a safe and efficacious anti-HIV microbicide is not yet available despite the fact that more than 60 candidate agents have been identified to have in vitro activity against HIV, several of which have advanced to clinical testing. Nonetheless, proof-of-concept of microbicides has been established based on the results of recent CAPRISA 004 clinical trials. In this article, the trends and challenges in the development of effective and safe microbicides to combat HIV transmission are reviewed. PMID:22310826
Keating, Sheila M; Jacobs, Evan S; Norris, Philip J
From early in the HIV epidemic it was appreciated that many inflammatory markers such as neopterin and TNF-α were elevated in patients with AIDS. With the advent of modern technology able to measure a broad array of cytokines, we now know that from the earliest points of infection HIV induces a cytokine storm. This review will focus on how cytokines are disturbed in HIV infection and will explore potential therapeutic uses of cytokines. These factors can be used directly as therapy during HIV infection, either to suppress viral replication or prevent deleterious immune effects of infection, such as CD4+ T cell depletion. Cytokines also show great promise as adjuvants in the development of HIV vaccines, which would be critical for the eventual control of the epidemic.
Bockting, W O; Robinson, B E; Rosser, B R
Although clinical experience and preliminary research suggest that some transgender people are at significant risk for HIV, this stigmatized group has so far been largely ignored in HIV prevention. As part of the development of HIV prevention education targeting the transgender population, focus groups of selected transgender individuals assessed their HIV risks and prevention needs. Data were gathered in the following four areas: (1) the impact of HIV/AIDS on transgender persons; (2) risk factors; (3) information and services needed; and (4) recruitment strategies. Findings indicated that HIV/AIDS compounds stigmatization related to transgender identity, interferes with sexual experimentation during the transgender 'coming out' process, and may interfere with obtaining sex reassignment. Identified transgender-specific risk factors include: sexual identity conflict, shame and isolation, secrecy, search for affirmation, compulsive sexual behaviour, prostitution, and sharing needles while injecting hormones. Community involvement, peer education and affirmation of transgender identity were stressed as integral components of a successful intervention. Education of health professionals about transgender identity and sexuality and support groups for transgender people with HIV/AIDS are urgently needed.
Lollini, Pier-Luigi; Cavallo, Federica; Nanni, Patrizia; Quaglino, Elena
Years of unsuccessful attempts at fighting established tumors with vaccines have taught us all that they are only able to truly impact patient survival when used in a preventive setting, as would normally be the case for traditional vaccines against infectious diseases. While true primary cancer prevention is still but a long-term goal, secondary and tertiary prevention are already in the clinic and providing encouraging results. A combination of immunopreventive cancer strategies and recently approved checkpoint inhibitors is a further promise of forthcoming successful cancer disease control, but prevention will require a considerable reduction of currently reported toxicities. These considerations summed with the increased understanding of tumor antigens allow space for an optimistic view of the future. PMID:26343198
Friedman, Samuel R; Downing, Martin J; Smyrnov, Pavlo; Nikolopoulos, Georgios; Schneider, John A; Livak, Britt; Magiorkinis, Gkikas; Slobodianyk, Liudmyla; Vasylyeva, Tetyana I; Paraskevis, Dimitrios; Psichogiou, Mina; Sypsa, Vana; Malliori, Melpomeni M; Hatzakis, Angelos
Current ideas about HIV prevention include a mixture of primarily biomedical interventions, socio-mechanical interventions such as sterile syringe and condom distribution, and behavioral interventions. This article presents a framework for socially-integrated transdisciplinary HIV prevention that may improve current prevention efforts. It first describes one socially-integrated transdisciplinary intervention project, the Transmission Reduction Intervention Project. We focus on how social aspects of the intervention integrate its component parts across disciplines and processes at different levels of analysis. We then present socially-integrated perspectives about how to improve combination antiretroviral treatment (cART) processes at the population level in order to solve the problems of the treatment cascade and make "treatment as prevention" more effective. Finally, we discuss some remaining problems and issues in such a social transdisciplinary intervention in the hope that other researchers and public health agents will develop additional socially-integrated interventions for HIV and other diseases.
Background There is a huge interest by faith-based organizations (FBOs) in sub-Saharan Africa and elsewhere in HIV prevention interventions that build on the religious aspects of being. Successful partnerships between the public health services and FBOs will require a better understanding of the conceptual framing of HIV prevention by FBOS to access for prevention intervention, those concepts the churches of various denominations and their members would support or endorse. This study investigated the conceptual framing of HIV prevention among church youths in Botswana; - a country with one of the highest HIV prevalence in the world. Method Participants were 213 Pentecostal church members (67% female; age range 12 to 23 years; median age = 19 years). We engaged the participants in a mixed-method inductive process to collect data on their implicit framing of HIV prevention concepts, taking into account the centrality of religion concepts to them and the moderating influences of age, gender and sexual experience. After, we analysed the data using multi-dimensional scaling (MDS) and hierarchical cluster analysis (HCA) to map the ways the church youths framed HIV prevention. Results The findings suggest the church youth to conceptually frame their HIV prevention from both faith-oriented and secular-oriented perspectives, while prioritizing the faith-oriented concepts based on biblical teachings and future focus. In their secular-oriented framing of HIV prevention, the church youths endorsed the importance to learn the facts about HIV and AIDS, understanding of community norms that increased risk for HIV and prevention education. However, components of secular-oriented framing of HIV prevention concepts were comparatively less was well differentiated among the youths than with faith-oriented framing, suggesting latent influences of the church knowledge environment to undervalue secular oriented concepts. Older and sexually experienced church youths in their framing
Vinzón, Sabrina E; Rösl, Frank
Cutaneous papillomaviruses are associated with specific skin diseases, such as extensive wart formation and the development of non-melanoma skin cancer (NMSC), especially in immunosuppressed patients. Hence, clinical approaches are required that prevent such lesions. Licensed human papillomavirus (HPV) vaccines confer type-restricted protection against HPV types 6, 11, 16 and 18, responsible of 90% of genital warts and 70% of cervical cancers, respectively. However, they do not protect against less prevalent high-risk types or cutaneous HPVs. Over the past few years, several studies explored the potential of developing vaccines targeting cutaneous papillomaviruses. These vaccines showed to be immunogenic and prevent skin tumor formation in certain animal models. Furthermore, under conditions mimicking the ones found in the intended target population (i.e., immunosuppression and in the presence of an already established infection before vaccination), recent preclinical data shows that immunization can still be effective. Strategies are currently focused on finding vaccine formulations that can confer protection against a broad range of papillomavirus-associated diseases. The state-of-the-art of these approaches and the future directions in the field will be presented. PMID:25692212
Shollenberger, Lisa M; Bui, Cac; Paterson, Yvonne; Allen, Kelsey; Harn, Donald
Vaccines for HIV, malaria and TB remain high priorities, especially for sub-Saharan populations. The question is: will vaccines currently in development for these diseases function in populations that have a high prevalence of helminth infection? Infection with helminth parasites causes immune suppression and a CD4+ Th2 skewing of the immune system, thereby impairing Th1-type vaccine efficacy. In this study, we conduct HIV vaccine trials in mice with and without chronic helminth infection to mimic the human vaccine recipient populations in Sub-Saharan Africa and other helminth parasite endemic regions of the world, as there is large overlap in global prevalence for HIV and helminth infection. Here, we demonstrate that Listeria monocytogenes functions as a vaccine vector to drive robust and functional HIV-specific cellular immune responses, irrespective of chronic helminth infection. This observation represents a significant advance in the field of vaccine research and underscores the concept that vaccines in the developmental pipeline should be effective in the target populations.
Lederman, Michael M; Jump, Robin; Pilch-Cooper, Heather A; Root, Michael; Sieg, Scott F
With the continuing march of the AIDS epidemic and little hope for an effective vaccine in the near future, work to develop a topical strategy to prevent HIV infection is increasingly important. This stated, the track record of large scale "microbicide" trials has been disappointing with nonspecific inhibitors either failing to protect women from infection or even increasing HIV acquisition. Newer strategies that target directly the elements needed for viral entry into cells have shown promise in non-human primate models of HIV transmission and as these agents have not yet been broadly introduced in regions of highest HIV prevalence, they are particularly attractive for prophylaxis. We review here the agents that can block HIV cellular entry and that show promise as topical strategies or "virustats" to prevent mucosal transmission of HIV infection PMID:19094217
No cure has been found for HIV/AIDS. Therefore, until one is found which is affordable and feasible for use in developing countries, preventing HIV infection is the best way to combat the HIV/AIDS pandemic. All of the many biological characteristics of HIV which affect its rate of spread in a population can be affected through individual behavior. The two most important behaviors which spread HIV are having sexual intercourse with an HIV-infected sex partner without using a condom and sharing unsterilized drug injecting equipment. Strategies to reduce risky behavior include providing information, lowering the costs of condom use and safe injecting behavior, and raising the costs of risky behavior. The costs of condom use include the financial and time costs of buying the condoms, the potential inconvenience and social embarrassment of buying and using them, and reduced pleasure among some users. IV drug users face the problems of getting into and remaining in drug treatment programs, and obtaining sterile injecting equipment. Government priorities in preventing HIV/AIDS and mobilizing political support against AIDS are discussed.
Downing, Martin J.; Smyrnov, Pavlo; Nikolopoulos, Georgios; Schneider, John A.; Livak, Britt; Magiorkinis, Gkikas; Slobodianyk, Liudmyla; Vasylyeva, Tetyana I.; Paraskevis, Dimitrios; Psichogiou, Mina; Sypsa, Vana; Malliori, Melpomeni M.; Hatzakis, Angelos
Current ideas about HIV prevention include a mixture of primarily biomedical interventions, sociomechanical interventions such as sterile syringe and condom distribution, and behavioral interventions. This article presents a framework for socially-integrated transdisciplinary HIV prevention that may improve current prevention efforts. It first describes one socially-integrated transdisciplinary intervention project, the Transmission Reduction Intervention Project. We focus on how social aspects of the intervention integrate its component parts across disciplines and processes at different levels of analysis. We then present socially-integrated perspectives about how to improve combination antiretroviral treatment (cART) processes at the population level in order to solve the problems of the treatment cascade and make “treatment as prevention” more effective. Finally, we discuss some remaining problems and issues in such a social transdisciplinary intervention in the hope that other researchers and public health agents will develop additional socially-integrated interventions for HIV and other diseases. PMID:24165983
Fisher, Celia B.
This research used open-ended and true-false questions to assess the preparedness of 96 ethnically diverse, economically and socially marginalized adult street drug users to consent to participate in HIV vaccine trials (HVT). Specific areas of consent vulnerability included misconceptions about: (1) the recuperative value and risk of vaccines in general; (2) the presence of the HIV virus within the vaccine and the possibility of contracting or transmitting HIV as a consequence of participation; (3) inclusion criteria and experimental blinds; and (4) distrust in the medical and research establishments. A brief HVT lesson administered to 30 participants was effective in correcting specific HVT knowledge misperceptions and increasing certain, but not all areas of HVT trust. Assessment of post-lesson responses to ethics-relevant questions provides information on respondents' attitudes toward AIDS safe behavior, research risks and benefits, monetary compensation, and willingness to participate. Implications for enhancing informed consent for HVT involving active drug users are discussed. PMID:20569151
Pettifor, Audrey; MacPhail, Catherine; Nguyen, Nadia; Rosenberg, Molly
Cash payments to improve health outcomes have been used for many years, however, their use for HIV prevention is new and the impact not yet well understood. We provide a brief background on the rationale behind using cash to improve health outcomes, review current studies completed or underway using cash for prevention of sexual transmission of HIV, and outline some key considerations on the use of cash payments to prevent HIV infections. We searched the literature for studies that implemented cash transfer programs and measured HIV or HIV-related outcomes. We identified 16 studies meeting our criteria; 10 are completed. The majority of studies have been conducted with adolescents in developing countries and payments are focused on addressing structural risk factors such as poverty. Most have seen reductions in sexual behavior and one large trial has documented a difference in HIV prevalence between young women getting cash transfers and those not. Cash transfer programs focused on changing risky sexual behaviors to reduce HIV risk suggest promise. The context in which programs are situated, the purpose of the cash transfer, and the population will all affect the impact of such programs; ongoing RCTs with HIV incidence endpoints will shed more light on the efficacy of cash payments as strategy for HIV prevention. PMID:22760738
Mylvaganam, Geetha H.; Silvestri, Guido; Amara, Rama Rao
Anti-viral T- and B- cell responses play a critical role in suppressing HIV and SIV replication during chronic infection. However, these infections are rarely controlled by the host immune response, and most infected individuals need lifelong antiretroviral therapy (ART). Recent advances in our understanding of how anti-HIV immune responses are elicited and regulated prompted a surge of interest in harnessing these responses to reduce the HIV "residual disease" that is present in ART-treated HIV-infected individuals. Novel approaches that are currently explored include both conventional therapeutic vaccines (i.e., active immunization strategies using HIV-derived immunogens) as well as the use of checkpoint blockers such as anti-PD-1 antibodies. These approaches appear promising as key components of complex therapeutic strategies aimed at curing HIV infection. PMID:25996629
Mylvaganam, Geetha H; Silvestri, Guido; Amara, Rama Rao
Anti-viral T-cell and B-cell responses play a crucial role in suppressing HIV and SIV replication during chronic infection. However, these infections are rarely controlled by the host immune response, and most infected individuals need lifelong antiretroviral therapy (ART). Recent advances in our understanding of how anti-HIV immune responses are elicited and regulated prompted a surge of interest in harnessing these responses to reduce the HIV 'residual disease' that is present in ART-treated HIV-infected individuals. Novel approaches that are currently explored include both conventional therapeutic vaccines (i.e., active immunization strategies using HIV-derived immunogens) as well as the use of checkpoint blockers such as anti-PD-1 antibodies. These approaches appear promising as key components of complex therapeutic strategies aimed at curing HIV infection.
Frew, Paula M; Archibald, Matthew; Martinez, Nina; del Rio, Carlos; Mulligan, Mark J
The HIV/AIDS pandemic continues to challenge the African American community with disproportionate rates of infection, particularly among young women ages 25 to 34 years. Development of a preventive HIV vaccine may bring a substantial turning point in this health crisis. Engagement of the African American community is necessary to improve awareness of the effort and favorably influence attitudes and referent norms. The Theory of Reasoned Action (TRA) may be a useful framework for exploration of community engagement outcomes including future attendance, community mobilization, and study participation. Within the context of HIV vaccine outreach, we conducted a cross-sectional survey in early 2007 with 175 African-American adults (>/= 18 years). Confirmatory factor analysis and structural equation modeling were performed and the findings support the potential of the model in understanding behavioral intentions toward HIV vaccine research.
Frew, Paula M.; Archibald, Matthew; Martinez, Nina; del Rio, Carlos; Mulligan, Mark J.
The HIV/AIDS pandemic continues to challenge the African American community with disproportionate rates of infection, particularly among young women ages 25 to 34 years. Development of a preventive HIV vaccine may bring a substantial turning point in this health crisis. Engagement of the African American community is necessary to improve awareness of the effort and favorably influence attitudes and referent norms. The Theory of Reasoned Action (TRA) may be a useful framework for exploration of community engagement outcomes including future attendance, community mobilization, and study participation. Within the context of HIV vaccine outreach, we conducted a cross-sectional survey in early 2007 with 175 African-American adults (≥ 18 years). Confirmatory factor analysis and structural equation modeling were performed and the findings support the potential of the model in understanding behavioral intentions toward HIV vaccine research. PMID:20686675
Singh, Dharmendra K; Kumar, Rajnish; Rai, Ruchi; Maurya, Manisha; Bhargava, Anudita
There is paucity of knowledge about the immunogenicity of vaccines in infants who have been exposed to HIV in-utero but have remained uninfected. The authors studied the immunogenicity of 3 doses of recombinant hepatitis B vaccine at 6,10,14 wk of age in HIV exposed but uninfected (HEU) infants. After 3 mo of last dose of the vaccine, out of 26 infants, 23 (89.5 %) infants were found to be responders (Anti HBs IgG titres ≥ 10 mIU/ml) and 3 (11.5 %) babies remained non responders (Anti HBs IgG titres < 10 mIU/ml). The proportion of babies who were non responders were higher when compared to similar studies done on unexposed and uninfected infants, suggesting a poorer immunogenicity of hepatitis B vaccine in these infants.
Kourkounti, Sofia; Papaizos, Vassilios; Leuow, Kirsten; Kordosis, Theodoros; Antoniou, Christina
Vaccination against hepatitis A is an important intervention to prevent disease in HIV-patients. There are insufficient data on the association of the response to hepatitis A vaccine with immunological parameters, including subpopulations of T-cells. We studied HIV-infected adults with CD4 T-cells>200 cells/mm(3) who received two doses of hepatitis A vaccine (Havrix or Vaqta). The counts of CD3, CD4, CD8, CD4+T-cells, NK, NK CD8+, NK CD8 - cells, and HIV RNA were measured at the time of first dose administration and one month after the end of the vaccination period. The geometric mean titer of antibodies to hepatitis A virus (anti-HAV) and factors affecting response were evaluated. 113 patients (50 antiretroviral treatment-naïve and 63 treatment-experienced) were enrolled in the study. There was no change in the immunological parameters and in the HIV-RNA post-vaccination, except for a decrease in CD8 and in double positive CD4+CD8+t-cell count. The immune response and geometric mean titer of anti-HAV were similar among treated and naïve patients (78% vs. 76% and 237 mIU/mL vs. 158 mIU/mL). Vaccine response was achieved in 71% of patients with CD4=200-499 cells/mm(3) compared with 80% of participants with CD4 ≥500 cells/mm(3) (p>0.05). Logistic regression revealed that immunological cells tested do not affect response differently in treatment-naïve vs. experienced patients. The only factor affecting response is the CD4 T-cell count at vaccination (OR 1.320; 95% CI 1.052-1.656; p=0.016). Patients with CD4 T-cell count ≥500 cells/mm(3) were 4.3 times more likely to respond to the vaccine than patients with CD4 T-cell count 200-499 cells/mm(3) (p=0.005). In conclusion, successful vaccination is associated with CD4 T-cells. The count of other immune cells or the administration of antiretroviral therapy does not predict response to hepatitis A vaccine in HIV patient with baseline CD4 T-cell>200 cells/mm(3).
Sauce, Delphine; Gorochov, Guy; Larsen, Martin
Understanding the factors that delineate the efficacy of T-cell responses towards pathogens is crucial for our ability to develop potent therapies and vaccines against infectious diseases, such as HIV. Here we show that a recently developed analytical tool, the polyfunctionality index (PI), not only enables prediction of protection after vaccination against HIV, but also allows identification of the immunological pathways involved. Our data suggest that induction of a synergistic network of CD4+ T-cell subsets is implicated in HIV-protection. Accordingly, we provide evidence that vaccine-induced protection is associated with CD40L expressing Th2 cells and IL-2 secreting Th17 cells. In conclusion, we describe a novel approach that is widely applicable and readily interpretable in a biological and clinical context. This approach could greatly impact our fundamental understanding of T-cell immunity as well as the search for effective vaccines. PMID:27324186
Jeffrey Fessel, W
For a decade, attempts to produce a vaccine that prevents HIV infection have been fruitless, and fresh approaches are required. Apobec3G is a natural defensin and a cytidine deaminase. Apobec3G induces a high rate of dC to dU mutation in the first minus strand of cDNA, causing degradation throughout the HIV genome that renders the virus effete. The viral infectivity factor (vif) of HIV is essential for efficient replication of that virus. Vif binds to apobec3G and induces its polyubiquitination, which enables HIV to evade apobec3G. This suggests that a vif-based vaccine which induced anti-vif antibodies, would prevent the neutralizing action of vif upon apobec3G. Then, with HIV-vif ineffective, apobec3G could act without hindrance to create a less aggressive, non-lethal HIV infection. Mutated vif impedes HIV infection. Slow progressors with vif 132S had 4-fold lower viral loads than those with vif 132R; and introducing vif 132S into HIV-1 caused a 5-fold decrease in viral replication. And in the absence of vif, HIV virions accumulate multiple defects in structural, enzymatic, and regulatory viral proteins. The success of a vif-based vaccine depends upon (1) a vif-antibody response, and (2) vif antibodies entering the cells that harbor HIV. First, antibodies to vif have been seen in frequencies ranging between 25% and 100% in patients infected with HIV-1. Second, transport of anti-vif antibodies into cells might occur via several mechanisms. Likeliest is that in viremic persons, antibodies would attach to cell-free virions which would piggyback the antibodies into CD4+ cells. Alternatively, a fusion protein between vif and a cell-surface receptor, e.g., CD4 or CCR5, might be used as vaccine antigen. Also, anti-vif antibodies might internalize after ligation of HIV virions budding on the cell surface, in the same way as monoclonal antibodies against porcine pseudorabies virus induced viral glycoproteins on the cell surface to internalize. Finally, monoclonal
Brenner, Bluma G; Wainberg, Mark A
The success of the HIV Prevention Trials Network 052 trial has led to revisions in HIV-1 treatment guidelines. Antiretroviral therapy may reduce the risk of HIV-1 transmissions at the population level. The design of successful treatment as prevention interventions will be predicated on a comprehensive understanding of the spatial, temporal, and biological dynamics of heterosexual men who have sex with men and intravenous drug user epidemics. Viral phylogenetics can capture the underlying structure of transmission networks based on the genetic interrelatedness of viral sequences and cluster networks that could not be otherwise identified. This article describes the phylogenetic expansion of the Montreal men who have sex with men epidemic over the last decade. High rates of coclustering of primary infections are associated with 1 infection leading to 13 onward transmissions. Phylogeny substantiates the role of primary and recent stage infection in transmission dynamics, underlying the importance of timely diagnosis and immediate antiretroviral therapy initiation to avert transmission cascades.
Brown, Scott A.; Surman, Sherri L.; Sealy, Robert; Jones, Bart G.; Slobod, Karen S.; Branum, Kristen; Lockey, Timothy D.; Howlett, Nanna; Freiden, Pamela; Flynn, Patricia; Hurwitz, Julia L.
Currently, there are more than 30 million people infected with HIV-1 and thousands more are infected each day. Vaccination is the single most effective mechanism for prevention of viral disease, and after more than 25 years of research, one vaccine has shown somewhat encouraging results in an advanced clinical efficacy trial. A modified intent-to-treat analysis of trial results showed that infection was approximately 30% lower in the vaccine group compared to the placebo group. The vaccine was administered using a heterologous prime-boost regimen in which both target antigens and delivery vehicles were changed during the course of inoculations. Here we examine the complexity of heterologous prime-boost immunizations. We show that the use of different delivery vehicles in prime and boost inoculations can help to avert the inhibitory effects caused by vector-specific immune responses. We also show that the introduction of new antigens into boost inoculations can be advantageous, demonstrating that the effect of ‘original antigenic sin’ is not absolute. Pre-clinical and clinical studies are reviewed, including our own work with a three-vector vaccination regimen using recombinant DNA, virus (Sendai virus or vaccinia virus) and protein. Promising preliminary results suggest that the heterologous prime-boost strategy may possibly provide a foundation for the future prevention of HIV-1 infections in humans. PMID:20407589
Zhao, Chongbo; Ao, Zhujun; Yao, Xiaojian
HIV-1 virus-like particles (VLPs) are promising vaccine candidates against HIV-1 infection. They are capable of preserving the native conformation of HIV-1 antigens and priming CD4+ and CD8+ T cell responses efficiently via cross presentation by both major histocompatibility complex (MHC) class I and II molecules. Progress has been achieved in the preclinical research of HIV-1 VLPs as prophylactic vaccines that induce broadly neutralizing antibodies and potent T cell responses. Moreover, the progress in HIV-1 dendritic cells (DC)-based immunotherapy provides us with a new vision for HIV-1 vaccine development. In this review, we describe updates from the past 5 years on the development of HIV-1 VLPs as a vaccine candidate and on the combined use of HIV particles with HIV-1 DC-based immunotherapy as efficient prophylactic and therapeutic vaccination strategies. PMID:26805898
Byrom, Elizabeth, Ed.; Katz, Ginger, Ed.
This guide was developed out of a 5-year project aimed at preventing the transmission of the human immunodeficiency virus (HIV) by promoting HIV prevention and AIDS (acquired immunodeficiency syndrome) education in school health programs. This document includes recommendations of a January, 1989 forum which addressed HIV prevention education for…
Barnabas, Ruanne V; Wasserheit, Judith N; Huang, Yunda; Janes, Holly; Morrow, Rhoda; Fuchs, Jonathan; Mark, Karen E; Casapia, Martin; Mehrotra, Devan V; Buchbinder, Susan P; Corey, Lawrence
Introduction Extensive observational data suggest that HSV-2 infection may facilitate HIV acquisition, increase HIV viral load, and accelerate HIV progression and onward transmission. To explore these relationships, we examined the impact of pre-existing HSV-2 infection in an international HIV vaccine trial. Methods We analyzed the associations between prevalent HSV-2 infection and HIV-1 acquisition and progression among 1836 men who have sex with men (MSM). We used Cox proportional hazards regression models to estimate the association between HSV-2 infection and both HIV acquisition and ART initiation, and linear regression to explore the effect of HSV-2 on pre-ART viral load. Results HSV-2 infection increased risk of HIV-1 acquisition among all volunteers (adjusted hazard ratio 2.2; 95% CI, 1.4 to 3.5). Adjusting for demographic variables, circumcision, Ad5 titer and significant risk behaviors, the risk of HIV acquisition among HSV-2 infected placebo recipients was three fold higher than HSV-2 seronegatives (hazard ratio 3.3; 95% CI, 1.6 to 6.9). Past HSV-2 infection was associated with a 0.2 log10 copies/ml higher adjusted mean set point viral load (95% CI, 0.3 lower to 0.6 higher). HSV-2 infection was not associated with time to ART initiation. Conclusions Among MSM in an HIV-1 vaccine trial, pre-existing HSV-2 infection was a major risk factor for HIV acquisition. Past HSV-2 did not significantly increase HIV viral load or early disease progression. HSV-2 seropositive persons will likely prove more difficult than HSV-2 seronegative persons to protect against HIV infection using vaccines or other prevention strategies. PMID:21860356
Cano, C A
The application of a preventive HIV vaccine is the only hope for most developing countries to halt the AIDS pandemic. A project aimed to develop a preventive AIDS vaccine is being carried out since 1992 by three Cuban research institutions: Centro de Ingeniería Genética y Biotecnologia de La Habana, Instituto de Medicina Tropical 'Pedro Kouri' and Laboratorio de Investigaciones de SIDA de La Habana. The project includes two main strategies: (a) generation of recombinant multi-epitope polypeptides (MEPs) bearing several copies of the V3 loop from different HIV-1 isolates; and (b) development of immunogens capable of inducing a cytotoxic T cell response (CTL) specific for human immunodeficiency virus type 1 (HIV-1) antigens. This article summarizes the work in the first of these strategies. Based on the sequence of the V3 loop of HIV-1 we constructed a series of MEPs and evaluated their immunogenicity in mice, rabbits and macaques. The MEP TAB9, containing six V3 epitopes from isolates LR10, JY1, RF, MN, BRVA and IIIB, was selected together with the oil adjuvant Montanide ISA720 (SEPPIC, France) to perform a Phase I clinical trial in HIV seronegative Cuban volunteers. The trial was double blinded, randomized, and fulfilled all ethical and regulatory requirements. All TAB9 vaccinated volunteers developed a strong immune response and neutralizing antibodies were observed in the 50% of the subjects. However the second and third inoculations of the vaccine were not well tolerated because transient severe local reactions appeared in some individuals. A new formulation of TAB9 is currently in pre-clinical studies and is expected to enter clinical trials in 1999.
Gilbert, Peter B.; Sun, Yanqing
This article develops hypothesis testing procedures for the stratified mark-specific proportional hazards model in the presence of missing marks. The motivating application is preventive HIV vaccine efficacy trials, where the mark is the genetic distance of an infecting HIV sequence to an HIV sequence represented inside the vaccine. The test statistics are constructed based on two-stage efficient estimators, which utilize auxiliary predictors of the missing marks. The asymptotic properties and finite-sample performances of the testing procedures are investigated, demonstrating double-robustness and effectiveness of the predictive auxiliaries to recover efficiency. The methods are applied to the RV144 vaccine trial. PMID:25641990
... medlineplus.gov/news/fullstory_163464.html Screening, HPV Vaccine Can Prevent Cervical Cancer: FDA Agency recommends getting ... by the human papillomavirus (HPV). An FDA-approved vaccine called Gardasil 9 protects against 9 HPV types ...
Gupta, G R
The Women and AIDS Research Program (International Center for Research on Women) has identified a series of obstacles to preventing HIV infection among women, including social norms that mandate female ignorance about sexual matters, women's economic dependence on men, widespread acceptance of male promiscuity, and violence against women. Most AIDS prevention programs fail to challenge these contextual determinants and continue to focus on the promotion of condom use among men. Recommendations to empower women and improve their status are dismissed as long-term measures outside the domain of AIDS prevention. Feasible, however, is the modification of existing AIDS prevention programs to ensure they are gender-sensitive. This would mean measures such as providing services at times that are convenient to women and integrating services to reduce waiting and travelling times. To address the contextual issues at the root of women's vulnerability to HIV, AIDS prevention programs can link up with economic interventions such as credit programs, agricultural extension services, and women's cooperatives. Moreover, AIDS programs can provide HIV-infected women with social support through group educational sessions or counseling. Finally, because improvements in women's socioeconomic status are essential for the success of all AIDS prevention, program managers should be in the forefront of broader struggles to enact policy changes to eliminate gender-based discrimination and inequality.
Roberts, Kathleen Johnston; Newman, Peter A.; Duan, Naihua; Rudy, Ellen T.
HIV vaccines offer the best long-term hope of controlling the AIDS pandemic. We explored HIV vaccine knowledge and beliefs among communities at elevated risk for HIV/AIDS. Participants (N=99; median age=33 years; 48% female; 22% African-American; 44% Latino; 28% white; 6% other) were recruited from seven high-risk venues in Los Angeles, California, using purposive, venue-based sampling. Results from nine focus groups revealed: 1) mixed beliefs and conspiracy theories about the existence of HIV vaccines; 2) hopefulness and doubts about future HIV vaccine availability; 3) lack of information about HIV vaccines; and 4) confusion about vaccines and how they work. Tailored HIV vaccine education that addresses the current status of HIV vaccine development and key vaccine concepts is warranted among communities at risk. Ongoing dialogue among researchers, public health practitioners and communities at risk may provide a vital opportunity to dispel misinformation and rumors and to cultivate trust, which may facilitate HIV vaccine trial participation and uptake of future HIV vaccines. PMID:16396058
Frew, Paula M; del Rio, Carlos; Clifton, Sarah; Archibald, Matthew; Hormes, Joseph T; Mulligan, Mark J
The purpose of this exploratory study was to examine personal characteristics, socio-environmental conditions, and motivational factors that potentially influence HIV vaccine research community engagement. Specifically, the study identified predictive aspects that may aid in future community program development on HIV vaccine issues. A cross-sectional survey consisting of evaluative measures, demographics, social interaction, and health information-seeking behaviors was conducted. Participants were a diverse group of 452 adults (>or=18 years) at HIV vaccine awareness-building and community education gatherings in Atlanta. The sample included large numbers of women (n=251) and minorities (n=224). In multivariate analysis, the overall logistic regression model was significant, with a resulting coefficient of determination (Nagelkerke R(2)) of .505. Highly significant factors included an excellent activity/event rating (log odds beta = 4.521, P< .001), White race (beta= -.835, P= .005), greater educational attainment (beta= .725, P= .011), travel distance (beta = 1.186, P= .002), and excellent perception of the study site (beta=2.131, P< .001). Subgroup analyses by gender and race revealed similar findings. These data demonstrate the importance of building a favorable study site image and gaining familiarity in the community to aid in the promotion of HIV vaccine research on an ongoing basis.
Extended Follow-up Confirms Early Vaccine-Enhanced Risk of HIV Acquisition and Demonstrates Waning Effect Over Time Among Participants in a Randomized Trial of Recombinant Adenovirus HIV Vaccine (Step Study)
Duerr, Ann; Huang, Yunda; Buchbinder, Susan; Coombs, Robert W.; Sanchez, Jorge; del Rio, Carlos; Casapia, Martin; Santiago, Steven; Gilbert, Peter; Corey, Lawrence; Robertson, Michael N.
Background. The Step Study tested whether an adenovirus serotype 5 (Ad5)–vectored human immunodeficiency virus (HIV) vaccine could prevent HIV acquisition and/or reduce viral load set-point after infection. At the first interim analysis, nonefficacy criteria were met. Vaccinations were halted; participants were unblinded. In post hoc analyses, more HIV infections occurred in vaccinees vs placebo recipients in men who had Ad5-neutralizing antibodies and/or were uncircumcised. Follow-up was extended to assess relative risk of HIV acquisition in vaccinees vs placebo recipients over time. Methods. We used Cox proportional hazard models for analyses of vaccine effect on HIV acquisition and vaccine effect modifiers, and nonparametric and semiparametric methods for analysis of constancy of relative risk over time. Results. One hundred seventy-two of 1836 men were infected. The adjusted vaccinees vs placebo recipients hazard ratio (HR) for all follow-up time was 1.40 (95% confidence interval [CI], 1.03–1.92; P = .03). Vaccine effect differed by baseline Ad5 or circumcision status during first 18 months, but neither was significant for all follow-up time. The HR among uncircumcised and/or Ad5-seropositive men waned with time since vaccination. No significant vaccine-associated risk was seen among circumcised, Ad5-negative men (HR, 0.97; P = 1.0) over all follow-up time. Conclusions. The vaccine-associated risk seen in interim analysis was confirmed but waned with time from vaccination. Clinical Trials Registration. NCT00095576. PMID:22561365
Theiler, James; Yoon, Hyejin; Yusim, Karina; Picker, Louis J.; Fruh, Klaus; Korber, Bette
Epigraph is an efficient graph-based algorithm for designing vaccine antigens to optimize potential T-cell epitope (PTE) coverage. Epigraph vaccine antigens are functionally similar to Mosaic vaccines, which have demonstrated effectiveness in preliminary HIV non-human primate studies. In contrast to the Mosaic algorithm, Epigraph is substantially faster, and in restricted cases, provides a mathematically optimal solution. Epigraph furthermore has new features that enable enhanced vaccine design flexibility. These features include the ability to exclude rare epitopes from a design, to optimize population coverage based on inexact epitope matches, and to apply the code to both aligned and unaligned input sequences. Epigraph was developed to provide practical design solutions for two outstanding vaccine problems. The first of these is a personalized approach to a therapeutic T-cell HIV vaccine that would provide antigens with an excellent match to an individual’s infecting strain, intended to contain or clear a chronic infection. The second is a pan-filovirus vaccine, with the potential to protect against all known viruses in the Filoviradae family, including ebolaviruses. A web-based interface to run the Epigraph tool suite is available (http://www.hiv.lanl.gov/content/sequence/EPIGRAPH/epigraph.html). PMID:27703185
Excler, Jean-Louis; Ake, Julie; Robb, Merlin L; Kim, Jerome H; Plotkin, Stanley A
Animal and human data from various viral infections and vaccine studies suggest that nonneutralizing antibodies (nNAb) without neutralizing activity in vitro may play an important role in protection against viral infection in vivo. This was illustrated by the recent human immunodeficiency virus (HIV) RV144 vaccine efficacy trial, which demonstrated that HIV-specific IgG-mediated nNAb directed against the V2 loop of HIV type 1 envelope (Env) were inversely correlated with risk for HIV acquisition, while Env-specific plasma IgA-mediated antibodies were directly correlated with risk. However, tier 1 NAb in the subset of responders with a low level of plasma Env-specific IgA correlated with decreased risk. Nonhuman primate simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) challenge studies suggest that Env-mediated antibodies are essential and sufficient for protection. A comparison of immune responses generated in human efficacy trials reveals subtle differences in the fine specificities of the antibody responses, in particular in HIV-specific IgG subclasses. The underlying mechanisms that may have contributed to protection against HIV acquisition in humans, although not fully understood, are possibly mediated by antibody-dependent cell-mediated cytotoxicity (ADCC) and/or other nonneutralizing humoral effector functions, such as antibody-mediated phagocytosis. The presence of such functional nNAb in mucosal tissues and cervico-vaginal and rectal secretions challenges the paradigm that NAb are the predominant immune response conferring protection, although this does not negate the desirability of evoking neutralizing antibodies through vaccination. Instead, NAb and nNAb should be looked upon as complementary or synergistic humoral effector functions. Several HIV vaccine clinical trials to study these antibody responses in various prime-boost modalities in the systemic and mucosal compartments are ongoing. The induction of high
Pitisuttithum, Punnee; Rerks-Ngarm, Supachai; O’Connell, Robert J.; Kim, Jerome H.; Excler, Jean-Louis
Recent advances in HIV vaccine development along with a better understanding of the immune correlates of risk have emerged from the RV144 efficacy trial conducted in Thailand. Epidemiological data suggest that CRF01_AE is still predominant in South-East Asia and is spreading in China with a growing number of circulating recombinant forms due to increasing human contact, particularly in large urban centers, tourist locations and in sites of common infrastructure. A vaccine countering CRF01_AE is a priority for the region. An Asia HIV vaccine against expanding B/E or BCE recombinant forms should be actively pursued. A major challenge that remains is the conduct of efficacy trials in heterosexual populations in this region. Men who have sex with men represent the main target population for future efficacy trials in Asia. Coupling HIV vaccines with other prevention modalities in efficacy trials might also be envisaged. These new avenues will only be made possible through the conduct of large-scale efficacy trials, interdisciplinary teams, international collaborations, and strong political and community commitments. PMID:26344118
Pitisuttithum, Punnee; Rerks-Ngarm, Supachai; O'Connell, Robert J; Kim, Jerome H; Excler, Jean-Louis
Recent advances in HIV vaccine development along with a better understanding of the immune correlates of risk have emerged from the RV144 efficacy trial conducted in Thailand. Epidemiological data suggest that CRF01_AE is still predominant in South-East Asia and is spreading in China with a growing number of circulating recombinant forms due to increasing human contact, particularly in large urban centers, tourist locations and in sites of common infrastructure. A vaccine countering CRF01_AE is a priority for the region. An Asia HIV vaccine against expanding B/E or BCE recombinant forms should be actively pursued. A major challenge that remains is the conduct of efficacy trials in heterosexual populations in this region. Men who have sex with men represent the main target population for future efficacy trials in Asia. Coupling HIV vaccines with other prevention modalities in efficacy trials might also be envisaged. These new avenues will only be made possible through the conduct of large-scale efficacy trials, interdisciplinary teams, international collaborations, and strong political and community commitments.
In contrast to other countries in Southeast Asia, the HIV/ AIDS epidemic is in the initial stages in Viet Nam, although the rates have increased notably since 1997. This study examined attitudes towards the use of an HIV vaccine (when one becomes available) as a means for preventing the disease. Since injecting drug users are the great majority of…
Sheppard, Haynes W
Inactivated or "killed" virus (KV) is a "classical" approach that has produced safe and effective human and veterinary vaccines but has received relatively little attention in the effort to develop an HIV/AIDS vaccine. Initially, KV and rgp120 subunit vaccines were the two most obvious approaches but, unfortunately, rgp120 has not been efficacious and the KV approach has been limited by a variety of scientific, technical, and sociological factors. For example, when responses to cellular antigens, present on SIV grown in human cells, proved to be largely responsible for efficacy, the KV approach was widely discounted. Similarly, when lab-adapted HIV-1 appeared to lose envelope glycoprotein during preparation (not the case for primary isolates), this was viewed as a fundamental barrier to the KV concept. Also, a preference for "safer", genetically-engineered vaccines, and emphasis on cellular immunity, have left KV low on the priority list for funding agencies and investigators. The recent suggestion that "native" trimeric gp120 displays conserved conformational neutralization epitopes, along with the failure of rgp120, and difficulties in raising strong cellular responses with DNA or vectored vaccines, has restored some interest in the KV concept. In the past 15 years, several groups have initiated pre-clinical development of KV candidates for SIV or HIV and promising, albeit limited, information has been produced. In this chapter we discuss the rationale (including pros and cons) for producing and testing killed-HIV vaccines, the prospects for success, the nature and scope of research needed to test the KV concept, what has been learned to date, and what remains undone.
Pantin, Hilda; Schwartz, Seth J.; Sullivan, Summer; Prado, Guillermo; Szapocznik, José
The purpose of this article is to illustrate how an ecodevelopmental perspective on risk and protection can be applied to the study and prevention of unsafe sexual behavior in Hispanic immigrant adolescents. Special attention is given to culturally based ecodevelopmental risk and protective processes that may influence unsafe sexual behavior among Hispanic adolescents. Principles for designing prevention programs to offset these risks are offered on the basis of an ecodevelopmental HIV prevention program that has been developed and is currently being tested. PMID:15554814
Shapiro, Stuart Z
The HIV cure agenda has rekindled interest in the development of a therapeutic HIV vaccine. An iterative clinical trial strategy that proved successful for the development of effective cancer chemotherapies in the 1960s may be applicable to the development of a CD8 T lymphocyte-based therapeutic HIV vaccine. However, while cancer chemotherapy development could begin with iterative clinical trials to improve the use of active drugs, the first step in therapeutic HIV vaccine design should be discovery of immunogen constructs with potential for activity and their optimization to meet the challenges of HIV-1 sequence diversity and human polymorphism in T cell antigen presentation. A strategy for doing this is discussed in this article. The proposed strategy relies on a major commitment by funding organizations to fund organized and coordinated manufacture and clinical testing of a series of first- and second-generation constructs to test basic concepts in product design. This is presented as an alternative to funding a more traditional competition among private manufacturers and product champions of individual, already designed products.
Kramer, Victor G; Byrareddy, Siddappa N
The success of vaccine regimens against viral pathogens hinges on the elicitation of protective responses. Hypervariable pathogens such as HIV avoid neutralization by masking protective epitopes with more immunogenic decoys. The identification of protective, conserved epitopes is crucial for future vaccine candidate design. The strategies employed for identification of HIV protective epitopes will also aid towards rational vaccine design for other viral pathogens.
There is a logarithmic increase in the cost and complexity of the research and development process when transitioning a promising candidate vaccine from the laboratory into the clinic. Managing complex development programs involving people from diverse technical, cultural and geographical backgrounds is a specialised skill. It is essential that the group is clear on their objectives and how their activities affect others, that communication is open, inclusive and effective, and that the most rigorous, scientific approach based on statistical principles in compliance with regulatory requirements is used. Applying these standards to all vaccine development programs will filter out inappropriate candidates more readily and enhance the efficiency of vaccine development. The challenges of developing a new vaccine are illustrated in human immunodeficiency virus (HIV) vaccinology. Selecting vaccine candidates for HIV requires the ability to evaluate the large number of potential antigens in imperfect and non-standardised animal models. Further, using these models to evaluate questions such as dose scaling to humans, optimal route of administration, the use of adjuvants and potential formulation improvements adds variable to variable, making the interpretation of results particularly challenging. This may lead to the promotion of a poor candidate or the elimination of a good one. The absence of precise immunological correlates of protection and the prohibitive cost of confirmatory clinical trials are further significant barriers. However, there are practical steps that can be taken to standardise early vaccine evaluation, which would result in more efficient development of new vaccines for HIV and other disease areas with similarly challenging development issues (such as hepatitis C virus, influenza, Mycobacterium tuberculosis and malaria).
Spearman, Paul; Kalams, Spyros; Elizaga, Marnie; Metch, Barbara; Chiu, Ya-Lin; Allen, Mary; Weinhold, Kent J; Ferrari, Guido; Parker, Scott D; McElrath, M Juliana; Frey, Sharon E; Fuchs, Jonathan D; Keefer, Michael C; Lubeck, Michael D; Egan, Michael; Braun, Ralph; Eldridge, John H; Haynes, Barton F; Corey, Lawrence
There is an urgent need for a vaccine capable of preventing HIV infection or the development of HIV-related disease. A number of approaches designed to stimulate HIV-specific CD8+ cytotoxic T cell responses together with helper responses are presently under evaluation. In this phase 1, multi-center, placebo-controlled trial, we tested the ability of a novel multiepitope peptide vaccine to elicit HIV-specific immunity. To enhance the immunogenicity of the peptide vaccine, half of the vaccine recipients received recombinant granulocyte-macrophage colony stimulating factor (GM-CSF) protein as a coadjuvant. The vaccine was safe; tolerability was moderate, with a number of adverse events related to local injection site reactogenicity. Anti-GM-CSF antibody responses developed in the majority of GM-CSF recipients but were not associated with adverse hematologic events. The vaccine was only minimally immunogenic. Six of 80 volunteers who received vaccine developed HIV-specific responses as measured by interferon-gamma ELISPOT assay, and measurable responses were transient. This study failed to demonstrate that GM-CSF can substantially improve the overall weak immunogenicity of a multiepitope peptide-based HIV vaccine.
Giannini, Barbara; Gazzarata, Roberta; Sticchi, Laura; Giacomini, Mauro
Vaccination in HIV-infected patients constitutes an essential tool in the prevention of the most common infectious diseases. The Ligurian Vaccination in HIV Program is a proposed vaccination schedule specifically dedicated to this risk group. Selective strategies are proposed within this program, employing ICT (Information and Communication) tools to identify this susceptible target group, to monitor immunization coverage over time and to manage failures and defaulting. The proposal is to connect an immunization registry system to an existing regional platform that allows clinical data re-use among several medical structures, to completely manage the vaccination process. This architecture will adopt a Service Oriented Architecture (SOA) approach and standard HSSP (Health Services Specification Program) interfaces to support interoperability. According to the presented solution, vaccination administration information retrieved from the immunization registry will be structured according to the specifications within the immunization section of the HL7 (Health Level 7) CCD (Continuity of Care Document) document. Immunization coverage will be evaluated through the continuous monitoring of serology and antibody titers gathered from the hospital LIS (Laboratory Information System) structured into a HL7 Version 3 (v3) Clinical Document Architecture Release 2 (CDA R2).
Torabi, Mohammad R., Ed.
This second special issue of the Health Education Monograph Series on HIV/AIDS Prevention in Rural Communities presents seven articles: (1) "Preventing Maternal-Infant Transmission of HIV: Social and Ethical Issues" (James G. Anderson, Marilyn M. Anderson, and Tara Booth); (2) "HIV Infection in Diverse Rural Population: Migrant Farm…
Torabi, Mohammad R., Ed.
This third special issue of the Health Education Monograph Series on HIV/AIDS Prevention in Rural Communities presents 9 articles on: "Rural Adolescent Views of HIV Prevention: Focus Groups at Two Indiana Rural 4-H Clubs" (William L. Yarber and Stephanie A. Sanders); "Implementing HIV Education: Beyond Curriculum" (Susan…
Chanzu, Nadia; Ondondo, Beatrice
The field of HIV prevention has indeed progressed in leaps and bounds, but with major limitations of the current prevention and treatment options, the world remains desperate for an HIV vaccine. Sadly, this continues to be elusive, because more than 30 years since its discovery there is no licensed HIV vaccine. Research aiming to define immunological biomarkers to accurately predict vaccine efficacy have focused mainly on systemic immune responses, and as such, studies defining correlates of protection in the genitorectal mucosa, the primary target site for HIV entry and seeding are sparse. Clearly, difficulties in sampling and analysis of mucosal specimens, as well as their limited size have been a major deterrent in characterizing the type (mucosal antibodies, cytokines, chemokines, or CTL), threshold (magnitude, depth, and breadth) and viral inhibitory capacity of HIV-1-specific immune responses in the genitorectal mucosa, where they are needed to immediately block HIV acquisition and arrest subsequent virus dissemination. Nevertheless, a few studies document the existence of HIV-specific immune responses in the genitorectal mucosa of HIV-infected aviremic and viremic controllers, as well as in highly exposed persistently seronegative (HEPS) individuals with natural resistance to HIV-1. Some of these responses strongly correlate with protection from HIV acquisition and/or disease progression, thus providing significant clues of the ideal components of an efficacious HIV vaccine. In this study, we provide an overview of the key features of protective immune responses found in HEPS, elite and viremic controllers, and discuss how these can be achieved through mucosal immunization. Inevitably, HIV vaccine development research will have to consider strategies that elicit potent antibody and cellular immune responses within the genitorectal mucosa or induction of systemic immune cells with an inherent potential to home and persist at mucosal sites of HIV entry. PMID
Gentile, Angela; Bazán, Virginia
The Millennium Development Goals (MDGs), adopted by world leaders in the year 2000 with an aim to accomplish them by 2015, provide concrete benchmarks for tackling extreme poverty in its many dimensions. One aim is to reduce by two thirds the mortality rate among children <5 years of age. The deaths of nearly 3 million children under 5 each year worldwide can be attributed to diarrhea and pneumonia. Pneumonia, one form of pneumococcal disease, causes almost 1 in 5 deaths of children under 5 worldwide-more than 1.6 million children each year. Pneumococcal disease is preventable by vaccination; because antibiotic resistance is a growing problem worldwide, there is a great need to promote effective pneumococcal vaccines. Vaccines differ from other types of drugs, because they are administered to healthy individuals. Therefore, a good safety profile is required, there is a large governmental regulatory role, and low efficacy is unacceptable. Other important considerations are as follows: vaccines are often used in infants, are typically given in multiple doses, the manufacturing is a larger part of cost, requires high regulatory and quality control burden and minimization of costs. From a biological standpoint, the induction of vaccine-mediated protection is a complex procedure. Long-term protection typically requires the persistence of anti-microbial antibodies and/or the generation of immune memory cells capable of rapid and effective reactivation after microbial re-exposure. Appreciation of the predominant role of B cells in the efficacy of current vaccines should not minimize the importance of generating a T cell response, as this is essential for the induction of high affinity antibodies and immune memory. Pneumococcal capsular polysaccharides typically elicit B cell responses in a T-independent manner. Because of this, capsular polysaccharides are poorly immunogenic in children below 2 years of age and will generate an IgM isotype-based primary response with only
Waheed, Abdul A; Tachedjian, Gilda
The biomedical intervention that has had a major impact on the natural history of HIV and on the global HIV epidemic is antiretroviral therapy (ART). However, the emergence of drug-resistant HIV, an inevitable consequence of increasing use of antiretroviral drugs, poses a major threat to ART success. At the turn of this century, access to life-saving ART was accelerated in low and middle-income countries with the Millennium Development Goal of 15 million individuals receiving ART by 2015 expected to be achieved. However, ART access needs to continue to expand to help bring HIV under control by 2030. The standard of care for people living with HIV in resource- limited settings differs dramatically compared to high-income countries, and not unexpectedly, ART rollout in these settings has resulted in an increase in acquired and transmitted drug resistance. Also of concern, the same drug classes used for ART have been approved or are being progressed for HIV prevention and drug resistance could mitigate their effectiveness for treatment and prevention. In the absence of an effective HIV vaccine and cure, it is imperative that the antiretroviral drug pipeline contains new classes of HIV inhibitors that are active against circulating drug-resistant strains. Studies to advance our fundamental understanding of HIV replication needs to continue, including the interplay between virus and host cell factors, to identify and characterize new drug targets for chemotherapeutic intervention.
Soares, Andreia; Müller, Tracey L; Chege, Gerald K; Williamson, Anna-Lise; Burgers, Wendy A
Persistent T cell activation following immunization with HIV vaccines may increase HIV acquisition risk. We investigated the magnitude and kinetics of T cell activation following vaccination of rhesus macaques with a candidate HIV vaccine consisting of a recombinant DNA and MVA vaccination regimen. We show that global CD4+ and CD8+ T cell activation, as measured by the expression of Ki67 and Bcl-2, peaked one week after boosting with MVA, but then waned rapidly to pre-vaccination levels. Furthermore, increased frequencies of CD4+ CCR5+ T cells, which represent potential HIV target cells, were short-lived and decreased to baseline levels within two months. Activated CD4+ T cells were predominantly of a central memory phenotype, and activated CD8+ T cells were distributed between central and effector memory phenotypes. Thus, only transient changes in T cell activation occurred following poxvirus vaccination, indicating a lack of persistent immune activation.
Phillips-Guzman, Christina M; Martinez-Donate, Ana P; Hovell, Melbourne F; Blumberg, Elaine J; Sipan, Carol L; Rovniak, Liza S; Kelley, Norma J
Participation of different community sectors, including the private business sector, is necessary to fight the HIV/AIDS epidemic. Local businesses may be reluctant to participate in HIV prevention because of fear of negative customer reactions and loss of revenue. This study examines the extent to which residents of two communities in San Diego, California, would support HIV prevention initiatives in local businesses. A population-based household survey (N = 200) is conducted in two communities with higher versus lower risk for HIV. The survey includes questions regarding the acceptability of HIV prevention activities, such as condom and brochure distribution in businesses, and history of exposure to HIV prevention activities in local businesses. Most residents agree that (a) business involvement in prevention activities would reduce HIV (92%), (b) free or low-cost condoms available in businesses could prevent the spread of HIV (90.9%) and increase condom accessibility (87%), and (c) they would prefer to shop at businesses that supported HIV prevention versus those that did not (87.4%). These findings suggest that HIV prevention in local businesses would be supported by residents and would be unlikely to adversely affect business profits. This information could be used to design interventions to engage local businesses in HIV-prevention efforts.
... Past Emails CDC Features Pneumonia Can Be Prevented—Vaccines Can Help Language: English Español (Spanish) Recommend on ... like antibiotics and antivirals). Lower Your Risk with Vaccines In the United States, there are vaccines that ...
HIV's rapid global spread and the human suffering it has left in its wake have made AIDS a global heath priority for the 25 years since its discovery. Yet its capacity to rapidly evolve has made combating this virus a tremendous challenge. The obstacles to creating an effective HIV vaccine are formidable, but there are advances in the field on many fronts, in terms of novel vectors, adjuvants, and antigen design strategies. SIV live attenuated vaccine models are able to confer protection against heterologous challenge, and this continues to provide opportunities to explore the biological underpinnings of a protective effect (9). More indirect, but equally important, is new understanding regarding the biology of acute infection (43), the role of immune response in long-term non-progression (6,62, 81), and defining characteristics of broadly neutralizing antibodies (4). In this review we will focus on summarizing strategies directed towards a single issue, that of contending with HIV variation in terms of designing aT-cell vaccine. The strategies that prove most effective in this area can ultimately be combined with the best strategies under development in other areas, with the hope of ultimately converging on a viable vaccine candidate. Only two large HIV vaccine efficacy trials have been completed and both have failed to prevent infection or confer a benefit to infected individual (23,34), but there is ample reason to continue our efforts. A historic breakthrough came in 1996, when it was realized that although the virus could escape from a single antiretroviral (ARV) therapy, it could be thwarted by a combination of medications that simultaneously targeted different parts of the virus (HAART) (38). This revelation came after 15 years of research, thought, and clinical testing; to enable that vital progress the research and clinical communities had to first define and understand, then develop a strategy to counter, the remarkable evolutionary potential of the virus
Shedlock, Devon J; Silvestri, Guido; Weiner, David B
Rhesus macaques are an important animal model for the study of human disease and the development of vaccines against HIV and AIDS. HIV vaccines have been benchmarked in rhesus macaque preclinical challenge studies using chimeric viruses made up of parts of HIV and simian immunodeficiency viruses. However, the lack of efficacy in a recent clinical trial calls for a re-evaluation of the scientific assumptions regarding the predictive value of using data generated from rhesus macaques as a 'gatekeeper' for the advancement of candidate vaccines into the clinic. In this context, there is significant consensus among HIV vaccinologists that next-generation HIV vaccines must generate 'better' immunity in rhesus macaques than clinically unsuccessful vaccines generated using validated assays. Defining better immunity is the core challenge of HIV vaccine development in this system and is the focus of this Review.
Matoba, Nobuyuki; Magérus, Aude; Geyer, Brian C.; Zhang, Yunfang; Muralidharan, Mrinalini; Alfsen, Annette; Arntzen, Charles J.; Bomsel, Morgane; Mor, Tsafrir S.
A vaccine that would engage the mucosal immune system against a broad range of HIV-1 subtypes and prevent epithelial transmission is highly desirable. Here we report fusing the mucosal targeting B subunit of cholera toxin to the conserved galactosylceramide-binding domain (including the ELDKWA-neutralizing epitope) of the HIV-1 gp41 envelope protein, which mediates the transcytosis of HIV-1 across the mucosal epithelia. Chimeric protein expressed in bacteria or plants assembled into oligomers that were capable of binding galactosyl-ceramide and GM1 gangliosides. Mucosal (intranasal) administration in mice of the purified chimeric protein followed by an i.p. boost resulted in transcytosis-neutralizing serum IgG and mucosal IgA responses and induced immunological memory. Plant production of mucosally targeted immunogens could be particularly useful for immunization programs in developing countries, where desirable product traits include low cost of manufacture, heat stability, and needle-free delivery. PMID:15347807
Reuter, Morgan A; Pombo, Carolina; Betts, Michael R
Numerous studies have characterized the cytokine modulation observed in human immunodeficiency virus (HIV) infected individuals, from initial infection through chronic disease. Progressive and non-progressive HIV infection models show the cytokine milieu differs in terms of production and responsiveness in these two groups, suggesting an understanding of the role cytokines play during infection is necessary for directing the immune response toward viral control. This review will cover cytokine induction and dysfunction during HIV pathogenesis, with a focus on the interplay between cytokines and transcription factors, T cell activation, and exhaustion. We highlight cytokines that have either vaccine adjuvant or therapeutic potential and discuss the need to identify key factors required for prevention of progression, clearance of infection, or protection from acquisition.
Qiao, Chenmeng; Liu, Jiandong; Yang, Jun; Li, Yan; Weng, Jie; Shao, Yiming; Zhang, Xin
Human immunodeficiency virus (HIV) DNA vaccine can induce cellular and humoral immunity. A safe and effective HIV DNA vaccine is urgent need to prevent the spread of acquired immune deficiency syndrome (AIDS). The major drawback of DNA vaccines is the low immunogenicity, which is caused by the poor delivery to antigen presenting cells and insufficient antigen expression. Sparked by the capability of endosomal/lysosomal escape of the zwitterionic lipid distearoyl phosphoethanol-amine-polycarboxybetaine (DSPE-PCB), we attempted to develop a zwitterionic-based cationic liposome with enhanced immunogenicity of DNA vaccines. The mannosylated zwitterionic-based cationic liposome (man-ZCL) was constructed as a DNA vaccine adjuvant for HIV vaccination. Man-ZCL could complex with DNA antigens to form a tight structure and protect them from nuclei enzyme degradation. Benefited from the capability of the specific mannose receptor mediated antigen processing cells targeting and enhanced endosomal/lysosomal escape, the man-ZCL lipoplexes were supposed to promote antigen presentation and the immunogenicity of DNA vaccines. In vitro and in vivo results revealed that man-ZCL lipoplexes showed enhanced anti-HIV immune responses and lower toxicity compared with CpG/DNA and Lipo2k/DNA, and triggered a Th1/Th2 mixed immunity. An antigen-depot effect was observed in the administration site, and this resulted in enhanced retention of DNA antigens in draining lymph nodes. Most importantly, the man-ZCL could assist to activate T cells through a non-inflammasome pathway. These findings suggested that the man-ZCL could be potentially applied as a safe and efficient DNA adjuvant for HIV vaccines.
Lyons, Thomas; Osunkoya, Emmanuel; Anguh, Ivonne; Adefuye, Adedeji; Balogun, Joseph
The prevalence rate of HIV infection in jails and prisons is approximately 5 times the rate in the U.S. general population. The authors surveyed state prison officials to assess HIV testing and HIV prevention policies--specifically voluntary testing, group HIV prevention counseling, and peer education--in the 50 states and to determine whether those policies are associated with the characteristics of the state and its prison population.
Souza, Thiago Moreno L; Santini-Oliveira, Marilia; Martorelli, Andressa; Luz, Paula M; Vasconcellos, Mauricio T L; Giacoia-Gripp, Carmem B W; Morgado, Mariza; Nunes, Estevão P; Lemos, Alberto S; Ferreira, Ana C G; Moreira, Ronaldo I; Veloso, Valdiléa G; Siqueira, Marilda; Grinsztejn, Beatriz; Camacho, Luiz A B
HIV-infected individuals have a higher risk of serious illnesses following infection by infection with influenza. Although anti-influenza vaccination is recommended, immunosuppression may limit their response to active immunization. We followed-up a cohort of HIV-infected individuals vaccinated against influenza to assess the immunogenicity and sustainability of the immune response to vaccination. Individuals were vaccinated 2011 with inactivated triple influenza vaccine (TIV), and they had received in 2010 the monovalent anti-A(H1N1)pdm09 vaccine. The sustainability of the immune response to A(H1N1)pdm09 at 12 months after monovalent vaccination fell, both in individuals given two single or two double doses. For these individuals, A(H1N1)pdm09 component from TIV acted as a booster, raising around 40% the number of seroprotected individuals. Almost 70% of the HIV-infected individuals were already seroprotected to A/H3N2 at baseline. Again, TIV boosted over 90% the seroprotection to A/H3N2. Anti-A/H3N2 titers dropped by 20% at 6 months after vaccination. Pre-vaccination seroprotection rate to influenza B (victoria lineage) was the lowest among those tested, seroconversion rates were higher after vaccination. Seroconversion/protection after TIV vaccination did not differ significantly across categories of clinical and demographic variables. Anti-influenza responses in Brazilian HIV-infected individuals reflected both the previous history of virus circulation in Brazil and vaccination.
Lohman-Payne, Barb; Slyker, Jennifer; Rowland-Jones, Sarah L.
Synopsis Despite more than two decades of research, an effective vaccine that can prevent HIV-1 infection in populations exposed to the virus remains elusive. In the pursuit of an HIV-1 vaccine, does prevention of exposure to maternal HIV-1 in utero, at birth or in early life through breast-milk require special consideration? In this article we will review what is known about the immune mechanisms of susceptibility and resistance to mother-to-child transmission (MTCT) of HIV-1 and will summarise studies that have used passive or active immunisation strategies to interrupt -MTCT of HIV-1. We will also describe potentially modifiable infectious co-factors that may enhance transmission and/or disease progression (especially in the developing world). Ultimately an effective prophylactic vaccine against HIV-1 infection will need to be deployed as part of the Extended Programme of Immunisation (EPI) recommended by the World Health Organisation (WHO) for use in developing countries, so it is important to understand how the infant immune system responds to HIV-1 antigens, both in natural infection and presented by candidate vaccines. PMID:21078451
Davis, Tracy; Teaster, Pamela B.; Thornton, Alice; Watkins, John F.; Alexander, Linda; Zanjani, Faika
Purpose To explore primary care providers' HIV prevention practices for older adults. Primary care providers' perceptions and awareness were explored to understand factors that affect their provision of HIV prevention materials and HIV screening for older adults. Design and Method Data were collected through 24 semistructured interviews with primary care providers (i.e., physicians, physician assistants, and nurse practitioners) who see patients older than 50 years. Results Results reveal facilitators and barriers of HIV prevention for older adults among primary care providers and understanding of providers' HIV prevention practices and behaviors. Individual, patient, institutional, and societal factors influenced HIV prevention practices among participants, for example, provider training and work experience, lack of time, discomfort in discussing HIV/AIDS with older adults, stigma, and ageism were contributing factors. Furthermore, factors specific to primary and secondary HIV prevention were identified, for instance, the presence of sexually transmitted infections influenced providers' secondary prevention practices. Implications HIV disease, while preventable, is increasing among older adults. These findings inform future research and interventions aimed at increasing HIV prevention practices in primary care settings for patients older than 50. PMID:25736425
Pashov, Anastas; Canziani, Gabriela; Macleod, Stewart; Plaxco, Jason; Monzavi-Karbassi, Behjatolah; Kieber-Emmons, Thomas
Peptide mimotopes provide a strategy to augment human immunodeficiency virus 1 (HIV-1) specific carbohydrate reactive immune responses. Their antigenic and immunological properties will depend on the optimization of motif clustering and multimerization. We observe that structural variants of the same mimetic motif, linear versus cyclic, can be used to tune the properties of the antibodies elicited. The expansion of the database of mimotope sequence motifs can be increased by analyzing structures that bind to HIV directed monoclonal antibody 2G12 and the lectin Concanavalin A (Con A), fostering new mimotope designs. Such analysis indicates that these reagents bind to subsets of mannosyl antigens on the envelope (env) protein.
Scott, Yanille; Dezzutti, Charlene S.
Non-antiretroviral microbicide candidates were previously explored as a female-controlled method of preventing sexual transmission of HIV. These products contained non-HIV specific active compounds that were ultimately found to disrupt the vaginal epithelium, cause increased immune activation in the female genital tract, disturb vaginal flora, and/or cause other irritation that precluded their use as vaginal microbicides. Due to the failure of these first-generation candidates, there was a shift in focus to developing HIV pre-exposure prophylaxis and microbicides containing small-molecule antiretrovirals. Even with the limited success of the antiretroviral-based microbicides in clinical evaluations and no commercially available products, there has been significant progress in microbicide research. The lessons learned from previous trials have given rise to more rigorous preclinical evaluation that aims to be better at predicting microbicide efficacy and safety and to novel formulation and delivery technologies. These advances have resulted in renewed interest in developing non-antiretroviral-based microbicides, such as broadly neutralizing antibodies (for example, VRC01) and anti-viral proteins (for example, Griffithsin), as options for persons not wanting to use antiretroviral drugs, and for their potential to prevent multiple sexually transmitted infections. PMID:27438574
This essay discusses the rationale for targeting HIV prevention programs to the general public, as opposed to focusing strictly on high-risk populations. The author first considers varying definitions of the term "general public," then explains the goal of general public education programs. Additionally, the author lays down the theoretical foundations of general audience education programs and weights related research findings. Finally, he offers recommendations for future practice. Noting the complex socioecological elements involved in health behavior, the author argues in favor of a broad definition for the general public. This broad outlook allows programs to still target high-risk population while not bypassing low-risk persons, who are sometimes treated as irrelevant because they do not contribute to excess morbidity or mortality. When it comes to HIV educational programs for the general public, their goals should be to instruct the public on how the virus is transmitted, to allay unfounded fears, and to increase the level of support for AIDS prevention and control. Such a program would require a theoretical basis drawn from multiple sources: health education, health communication, clinical and social psychology, and social marketing. The author concludes by proving recommendations designed to reinforce existing programs: 1) strengthen efforts to ensure that all people are educated about HIV and to encourage people to treat AIDS patients with compassion; 2) continue to explore for the most effective communication channels; 3) strengthen the communication infrastructure for those who are disenfranchised from health education; and 4) strengthen evaluation efforts of health communication programs.
Swendeman, Dallas; Flannery, Diane; Rice, Eric; Adamson, David M.; Ingram, Barbara
We propose a set of common factors in evidence-based interventions (EBI) for HIV prevention, which cut across theoretical models of behavior change. Three existing literatures support this agenda: (1) Common factors in psychotherapy; (2) core elements from the Centers for Disease Control and Prevention EBIs; and (3) component analyses of EBI. To stimulate discussion among prevention researchers, we propose a set of common factors at the highest level of abstraction that describe what all effective programs do: (1) establish a framework to understand behavior change; (2) convey issue-specific and population-specific information necessary for healthy actions; (3) build cognitive, affective, and behavioral self-management skills; (4) address environmental barriers to implementing health behaviors; and (5) provide tools to develop ongoing social and community support for healthy actions. A focus on common factors will enhance research on new HIV prevention interventions, encourage collaboration among researchers, provide guidelines for adapting EBI, and simplify and speed the adoption of EBI for providers. PMID:18830813
Dale, C Jane; De Rose, Robert; Wilson, Kim M; Croom, Hayley A; Thomson, Scott; Coupar, Barbara E H; Ramsay, Alistair; Purcell, Damian F J; Ffrench, Rosemary; Law, Matthew; Emery, Sean; Cooper, David A; Ramshaw, Ian A; Boyle, David B; Kent, Stephen J
Induction of HIV-specific T-cell responses by vaccines may facilitate efficient control of HIV. Plasmid DNA vaccines and recombinant fowlpoxvirus (rFPV) vaccines are promising HIV-1 vaccine candidates, although either vaccine alone may be insufficient to protect against HIV-1. A consecutive immunisation strategy involving priming with DNA and boosting with rFPV vaccines encoding multiple common HIV-1 antigens was further evaluated in 30 macaques. The DNA vaccine vector included CpG immunostimulatory molecules, and rFPV vaccines were compared with rFPV vaccines co-expressing the pro-T cell cytokines IFNgamma or IL-12. Vaccines expressed multiple HIV-1 genes, mutated to remove active sites of the HIV proteins. The vaccines were well tolerated, and a significant enhancement of DNA-vaccine primed HIV-1 specific T lymphocyte responses was observed following rFPV boosting. Co-expression of IFNgamma or IL-12 by the rFPV vaccines did not further enhance immune responses. Non-sterilising protection from a non-pathogenic HIV-1 challenge was observed. This study provides evidence of a safe, optimised, strategy for the generation of T-cell mediated immunity to HIV-1.
Ruiz, P; Guynn, R W; Matorin, A A
HIV/AIDS has the unfortunate distinction of being one of the most devastating epidemics of the twentieth century. By the end of June, 1999, 420,201 deaths in persons with AIDS had been reported in the United States. While HIV/AIDS patients are currently living longer as a result of more effective and complex treatments, no vaccination or cure has yet been discovered. Over the years, the HIV/AIDS epidemic has become multifactorial and currently affects several different special population groups. Individuals who are at high risk for becoming infected with HIV or who already suffer from HIV/AIDS can benefit greatly from the interventions of psychiatrists or other mental health professionals. It is important that psychiatrists collaborate very closely with infectious disease specialists in the management of HIV/AIDS and its psychological sequelae. The authors describe the psychiatric conditions that most often occur in association with HIV/AIDS: mood disorders, anxiety disorders, substance-related disorders, psychotic disorders, insomnia and sleep disorders, delirium, dementia, and pain syndromes. We present guidelines for diagnosis and psychopharmacological and psychotherapeutic treatment of these disorders in patients with HIV/AIDS. The article concludes with a discussion of prevention strategies that can be used in a mental health treatment setting and special issues related to treating HIV/AIDS in certain special population groups.
Martinez, David R.; Permar, Sallie R.
Extensive studies have demonstrated that infant immune responses are distinct from those of adults. Despite these differences, infant immunization can elicit protective immune responses at levels comparable to or, in some cases, higher than adult immune responses to many vaccines. To date, only a few HIV vaccine candidates have been tested in infant populations, and none of them evaluated vaccine efficacy. Recent exciting studies showing that HIV-infected infants can develop broad neutralizing antibody responses and that some HIV vaccine regimens can elicit high levels of potentially protective antibodies in infants provide support for the development and testing of HIV vaccines in pediatric populations. In this review, we discuss the differences in adult and infant immune responses in the setting of HIV infection and vaccination. PMID:26656117
Yamamoto, Janet K.; Sanou, Missa P.; Abbott, Jeffrey R.; Coleman, James K.
Feline immunodeficiency virus (FIV) discovered in 1986 is a lentivirus that causes AIDS in domestic cats. FIV is classified into five subtypes (A–E), and all subtypes and circulating intersubtype recombinants have been identified throughout the world. A commercial FIV vaccine, consisting of inactivated subtype-A and –D viruses (Fel-O-Vax FIV, Fort Dodge Animal Health), was released in the United States in 2002. The United States Department of Agriculture approved the commercial release of Fel-O-Vax FIV based on two efficacy trials using 105 laboratory cats and a major safety trial performed on 689 pet cats. The prototype and commercial FIV vaccines had broad prophylactic efficacy against global FIV subtypes and circulating intersubtype recombinants. The mechanisms of cross-subtype efficacy are attributed to FIV-specific T-cell immunity. Findings from these studies are being used to define the prophylactic epitopes needed for an HIV-1 vaccine for humans. PMID:20210778
Venkatesh, Kartik K.
As antiretroviral treatment of HIV infection has become increasingly accessible, attention has focused on whether these drugs can used for prevention because of increased tolerability of newer medications, decreased cost, and the limitations of other approaches. We review the status of antiretroviral HIV prevention, including chemoprophylaxis, as well as the effects of treatment of infected individuals on prevention. It is possible that the life-saving agents that have transformed the natural history of AIDS can be a critical component of HIV prevention efforts, but their ultimate role in affecting HIV transmission dynamics remains to be defined. PMID:20724682
Ren, Xuqi; Ke, Wujian; Yang, Ligang; Huang, Shujie; Qin, Xiaolin
Background. The epidemiology of HPV in men who have sex with men (MSM) in Guangzhou, China, had not been reported previously. Methods. HIV-infected and HIV-uninfected MSM were recruited from a Guangzhou-based MSM clinic in 2013. Sociodemographic characteristics and sexual behaviors were collected. An anal cytological sample was taken for HPV testing. Results. We recruited 79 HIV-infected and 85 HIV-uninfected MSM. The median age was 26 years in both groups. The positivities of anal HPV of any type (81.0% versus 48.2%), any high risk type (50.6% versus 27.1%), any low risk type (55.7% versus 31.8%), and any 9-valent vaccine type (74.7% versus 36.5%) were all significantly higher among HIV-infected compared to that among HIV-negative MSM (p for all < 0.05). The great majority of HPV-infected MSM were infected with 9-valent vaccine types (59 out of 64 HIV-infected and 31 out of 41 HIV-uninfected). Anal bacterial infections were associated with higher anal HPV positivity and greater number of anal HPV types. Conclusion. Sexually active MSM in Guangzhou, especially those infected with HIV, had high and multiple HPV detections. The majority of these cases were potentially preventable by HPV vaccine. Regular anal exams and early HPV vaccination are warranted in this population. PMID:28133605
Holtgrave, David R; McGuire, Jean Flatley; Milan, Jesse
The Centers for Disease Control and Prevention has undertaken an advisory process to update its national HIV prevention plan. We offer observations on the magnitude of HIV prevention challenges in the United States and reflect on how these challenges might influence the structure of a new HIV prevention plan. We recommend a plan structure that (1) is based on fundamental principles of prevention, (2) enables accountability and mid-course correction, and (3) if achieved, would result in historic changes in the US HIV epidemic. The recommended plan structure would differentially prioritize serostatus determination and prevention and care interventions for people living with HIV while retaining goals directed at high-risk HIV-negative and general population members.
Chin'ombe, Nyasha; Ruhanya, Vurayai
More than decades have already elapsed since human immunodeficiency virus (HIV) was identified as the causative agent of acquired immunodeficiency syndrome (AIDS). The HIV has since spread to all parts of the world with devastating effects. In sub-saharan Africa, the HIV/AIDS epidemic has reached unprecedented proportions. Safe, effective and affordable HIV/AIDS vaccines for Africans are therefore urgently needed to contain this public health problem. Although, there are challenges, there are also scientific opportunities and strategies that can be exploited in the development of HIV/AIDS vaccines for Africa. The recent RV144 Phase III trial in Thailand has demonstrated that it is possible to develop a vaccine that can potentially elicit modest protective immunity against HIV infection. The main objective of this review is to outline the key scientific opportunities, challenges and strategies in HIV/AIDS vaccine development in Africa. PMID:26185576
Chin'ombe, Nyasha; Ruhanya, Vurayai
More than decades have already elapsed since human immunodeficiency virus (HIV) was identified as the causative agent of acquired immunodeficiency syndrome (AIDS). The HIV has since spread to all parts of the world with devastating effects. In sub-saharan Africa, the HIV/AIDS epidemic has reached unprecedented proportions. Safe, effective and affordable HIV/AIDS vaccines for Africans are therefore urgently needed to contain this public health problem. Although, there are challenges, there are also scientific opportunities and strategies that can be exploited in the development of HIV/AIDS vaccines for Africa. The recent RV144 Phase III trial in Thailand has demonstrated that it is possible to develop a vaccine that can potentially elicit modest protective immunity against HIV infection. The main objective of this review is to outline the key scientific opportunities, challenges and strategies in HIV/AIDS vaccine development in Africa.
Dayan, Gustavo H; Rubin, Steven
Increased reports of mumps in vaccinated populations prompted a review of the performance of mumps vaccines. The effectiveness of prior vaccination with 1 dose of vaccine ranged from 72.8% to 91% for the Jeryl Lynn strain, from 54.4% to 93% for the Urabe strain, and from 0% to 33% for the Rubini strain. Vaccine effectiveness after 2 doses of mumps vaccine was reported in 3 outbreaks and ranged from 91% to 94.6%. There was evidence of waning immunity, which is a likely factor in mumps outbreaks, aggravated by possible antigenic differences between the vaccine strain and outbreak strains. Inadequate vaccine coverage or use of the Rubini vaccine strain accounted for the majority of outbreaks reviewed; however, some outbreaks could not be prevented, despite high vaccination coverage with 2 doses of the Jeryl Lynn vaccine strain. Our findings indicate the need for more-effective mumps vaccines and/or for review of current vaccination policies to prevent future outbreaks.
Dolan, Kate; Larney, Sarah
Background & Objectives: HIV is a major health challenge for prison authorities. HIV in prisons has implications for HIV in the general community. The aim of this paper was to gather information on HIV risk, prevalence, prevention and treatment in prisons in India. Methods: Relevant published and unpublished reports and information were sought in order to provide a coherent picture of the current situation relating to HIV prevention, treatment and care in prisons in India. Information covered prison management and population statistics, general conditions in prisons, provision of general medical care and the HIV situation in prison. Results: No data on drug injection in prison were identified. Sex between men was reported to be common in some Indian prisons. A national study found that 1.7 per cent of inmates were HIV positive. Some prisons provided HIV education. Condom provision was considered illegal. A few prisoners received drug treatment for drug use, HIV infection or co-infection with sexually transmitted infections (STIs). Interpretation & conclusions: HIV prevalence in prisons in India was higher than that in the general community. Regular monitoring of information on HIV risk behaviours and prevalence in Indian prisons is strongly recommended. Evidence based treatment for drug injectors and nation-wide provision of HIV prevention strategies are urgently required. Voluntary counselling, testing and treatment for HIV and STIs should be provided. PMID:21245617
... prescribe PrEP, more HIV infections could be prevented. Health care providers can: Test patients for HIV as a regular part of ... Helping to monitor PrEP use and its effects. Health care providers can Test patients for HIV as a regular part of ...
Belyakov, I M; Ahlers, J D
Mucosal tissues are major sites of HIV entry and initial infection. Induction of a local mucosal cytotoxic T lymphocyte response is considered an important goal in developing an effective HIV vaccine. In addition, activation and recruitment of memory CD4(+) and CD8(+) T cells in systemic lymphoid circulation to mucosal effector sites might provide the firewall needed to prevent virus spread. Therefore a vaccine that generates CD4(+) and CD8(+) responses in both mucosal and systemic tissues might be required for protection against HIV. However, optimal routes and number of vaccinations required for the generation of long lasting CD4(+) and CD8(+) CTL effector and memory responses are not well understood especially for mucosal T cells. A number of studies looking at protective immune responses against diverse mucosal pathogens have shown that mucosal vaccination is necessary to induce a compartmentalized immune response including maximum levels of mucosal high-avidity CD8(+) CTL, antigen specific mucosal antibodies titers (especially sIgA), as well as induction of innate anti-viral factors in mucosa tissue. Immune responses are detectable at mucosal sites after systemic delivery of vaccine, and prime boost regimens can amplify the magnitude of immune responses in mucosal sites and in systemic lymphoid tissues. We believe that the most optimal mucosal and systemic HIV/SIV specific protective immune responses and innate factors might best be achieved by simultaneous mucosal and systemic prime and boost vaccinations. Similar principals of vaccination may be applied for vaccine development against cancer and highly invasive pathogens that lead to chronic infection.
Zwick, Michael B; Burton, Dennis R
Antibody (Ab) mediated neutralization is a crucial means of host resistance to many pathogens and will most likely be required in the development of a vaccine to protect against HIV-1. Here we examine mechanistic aspects of HIV-1 neutralization with attention to recent studies on the stoichiometric, kinetic and thermodynamic parameters involved. Neutralization of HIV-1, as with any microbe, minimally requires an initial molecular encounter with Ab. Ab occupancy of functional heterotrimers of the envelope glycoproteins, gp120 and gp41 (Env), indeed appears to be the dominant mechanism of neutralization for HIV-1. However, the Ab-binding site, the parameters mentioned above, as well as the stages and duration of vulnerability to Ab recognition, prior to and leading up to viral entry, each have a distinct impact on the mechanism of neutralization for any given Ab specificity. With HIV-1, the problems of mutational variation and neutralization resistance, coupled with the lability and conformational heterogeneity in Env, have stimulated the search for rational approaches to Env immunogen design that are unprecedented in vaccinology.
Live attenuated virus vaccines have shown the greatest potential to protect against simian immunodeficiency virus (SIV) infection, a model for human immunodeficiency virus (HIV). Immunity against the vaccine virus is thought to mediate protection. However, it is shown computationally that the opposite might be true. According to the model, the initial growth of the challenge strain, its peak load, and its potential to be pathogenic is higher if immunity against the vaccine virus is stronger. This is because the initial growth of the challenge strain is mainly determined by virus competition rather than immune suppression. The stronger the immunity against the vaccine strain, the weaker its competitive ability relative to the challenge strain, and the lower the level of protection. If the vaccine virus does protect the host against a challenge, it is because the competitive interactions between the viruses inhibit the initial growth of the challenge strain. According to these arguments, an inverse correlation between the level of attenuation and the level of protection is expected, and this has indeed been observed in experimental data. PMID:18586297
McMichael, Andrew J; Haynes, Barton F
A vaccine against human immunodeficiency virus (HIV) seems to be on the horizon. Correlates of risk of infection for the RV144 trial have been found. There is understanding of what makes HIV envelope–specific antibodies broadly neutralizing and new T cell vaccine approaches can overcome virus variability. PMID:22513323
An examination of age and sex or gender (sex/gender) in HIV vaccine preparedness studies can contribute to an understanding of these demographic variables in preparation for actual HIV vaccine trials. In this descriptive review, age and sex or gender (sex/gender) were examined in relation to willingness to participate (WTP) and retention in an HIV vaccine trial. Twenty-five articles were retrieved from the Organization for Economic Co-operation and Development (OECD) countries and 28 articles were retrieved from the non-OECD countries. In US studies that involved mainly white MSM, older men were more likely to be WTP in a hypothetical HIV vaccine trial and more likely to be retained than younger men. In most OECD studies, sex/gender was not associated with WTP in a hypothetical HIV vaccine trial, while females were more likely to be retained in most studies. Largely, age was not associated with WTP in the non-OECD countries, but the results on sex/gender were more variable. The relationship between adolescent or adult WTP in hypothetical HIV vaccine trials in South Africa did not appear to be modified by high school student status. In addition, more studies in discordant couples in the context of HIV vaccine preparedness could be conducted to examine gender roles and inequalities in preparation for HIV vaccine trials.
Harrison, Lee H
For decades, there was no licensed vaccine for prevention of endemic capsular group B meningococcal disease, despite the availability of vaccines for prevention of the other most common meningococcal capsular groups. Recently, however, two new vaccines have been licensed for prevention of group B disease. Although immunogenic and considered to have an acceptable safety profile, there are many scientific unknowns about these vaccines, including effectiveness against antigenically diverse endemic meningococcal strains; duration of protection; whether they provide any herd protection; and whether there will be meningococcal antigenic changes that will diminish effectiveness over time. In addition, these vaccines present societal dilemmas that could influence how they are used in the U.S., including high vaccine cost in the face of a historically low incidence of meningococcal disease. These issues are discussed in this review.
Harrison, Lee H
For decades, there was no licensed vaccine for prevention of endemic capsular group B meningococcal disease, despite the availability of vaccines for prevention of the other most common meningococcal capsular groups. Recently, however, two new vaccines have been licensed for prevention of group B disease. Although immunogenic and considered to have an acceptable safety profile, there are many scientific unknowns about these vaccines, including effectiveness against antigenically diverse endemic meningococcal strains; duration of protection; whether they provide any herd protection; and whether there will be meningococcal antigenic changes that will diminish effectiveness over time. In addition, these vaccines present societal dilemmas that could influence how they are used in the U.S., including high vaccine cost in the face of a historically low incidence of meningococcal disease. These issues are discussed in this review.
Takes, Robert P; Wierzbicka, Małgorzata; D'Souza, Gypsyamber; Jackowska, Joanna; Silver, Carl E; Rodrigo, Juan P; Dikkers, Frederik G; Olsen, Kerry D; Rinaldo, Alessandra; Brakenhoff, Ruud H; Ferlito, Alfio
Human papillomavirus (HPV) infections are well known causes of anogenital cancers. Recent studies show that HPV also plays a role in oropharyngeal cancer (OPC). A review on the role of HPV vaccination in the prevention of head and neck squamous cell carcinoma (HNSCC) with special emphasis on OPC was conducted and available vaccines and vaccination strategies in HNSCC and OPC are discussed. Prophylactic vaccination is known to be effective for prevention of anogenital HPV infection and precursor lesions in the cervix and anus. While the value of vaccination for prevention of OPC and possibly as an adjuvant treatment is still an open question, evidence to date supports the possibility that HPV vaccination may prove to be effective in reducing the incidence of this malignancy.
Kauffman, C; Hue, L
This article describes an adolescent, peer-education training program in Jamaica that was developed and operated by the Red Cross Societies of Jamaica and the US and was funded by AIDSCAP. The program aimed to develop a training system to prepare youth peer educators in preventing the spread of HIV infections and sexually transmitted diseases. The goal was to increase knowledge about, change attitudes toward, and develop prevention skills for HIV/AIDS. The initial program was to be replicated on a large scale and be sustainable over time. The program was developed in response to the 1500+ Jamaicans diagnosed with AIDS and the 20,000 or so with HIV infections. Transmission is mostly heterosexual. 15% of girls and 47% of boys are sexually active by 14 years of age, and almost 50% of syphilis and gonorrhea cases are among adolescents. The national training program relies on peer educators, aged 14-19 years, who are literate to the 6th-grade level. Training sessions are conducted for 10-21 persons/session for 27 hours over 3 weekends. Training relies on engaging games and activities. Trainees are taught how to facilitate 14 specific activities, including the correct way to use a condom. Peer educators work together in groups of twos or threes among groups of 10-15 adolescents, aged 10-15 years. By the third year of operation, most of the systems and materials were in place and the program expanded; cost-benefit analysis revealed that costs were returned. The program has continued with a variety of funds and delivery systems and new funding will likely shift the program emphasis. The program has survived with the enthusiasm and support of the trainers. Other start-up programs should ensure the involvement of youth at all stages of development.
CIANELLI, ROSINA; FERRER, LILIAN; MCELMURRY, BEVERLY J.
Socio-cultural factors and HIV-related misinformation contribute to the increasing number of Chilean women living with HIV. In spite of this, and to date, few culturally specific prevention activities have been developed for this population. The goal of the present study was to elicit the perspectives of low-income Chilean women regarding HIV and relevant socio-cultural factors, as a forerunner to the development of a culturally appropriate intervention. As part of a mixed-methods study, fifty low-income Chilean women participated in a survey and twenty were selected to participate in prevention, in-depth interviews. Results show evidence of widespread misinformation and misconceptions related to HIV/AIDS. Machismo and marianismo offer major barriers to prevention programme development. Future HIV prevention should stress partner communication, empowerment and improving the education of women vulnerable to HIV. PMID:18432428
Teitelman, Anne M.; Bevilacqua, Amanda W.; Jemmott, Loretta Sweet
Background: Women and adolescent girls bear a significant burden of the global HIV pandemic. Both behavioral and biomedical prevention approaches have been shown to be effective. In order to foster the most effective combination HIV-prevention approaches for women and girls, it is imperative to understand the unique biological, social, and structural considerations that increase vulnerability to acquiring HIV within this population. Primary Study Objective: The purpose of this article is to propose novel ideas for personalized biobehavioral HIV prevention for women and adolescent girls. The central argument is that we must transcend unilevel solutions for HIV prevention toward comprehensive, multilevel combination HIV prevention packages to actualize personalized biobehavioral HIV prevention. Our hope is to foster transnational dialogue among researchers, practitioners, educators, and policy makers toward the actualization of the proposed recommendations. Methods: We present a commentary organized to review biological, social, and structural factors that increase vulnerability to HIV acquisition among women and adolescent girls. The overview is followed by recommendations to curb HIV rates in the target population in a sustainable manner. Results: The physiology of the lower female reproductive system biologically increases HIV risk among women and girls. Social (eg, intimate partner violence) and structural (eg, gender inequality) factors exacerbate this risk by increasing the likelihood of viral exposure. Our recommendations for personalized biobehavioral HIV prevention are to (1) create innovative mechanisms for personalized HIV risk—reduction assessments; (2) develop mathematical models of local epidemics; (3) prepare personalized, evidence-based combination HIV risk—reduction packages; (4) structure gender equity into society; and (5) eliminate violence (both physical and structural) against women and girls. Conclusions: Generalized programs and
Nelwan, Erni J; Indrati, Agnes K; Isa, Ahmad; Triani, Nurlita; Alam, Nisaa Nur; Herlan, Maria S; Husen, Wahid; Pohan, Herdiman T; Alisjahbana, Bachti; Meheus, Andre; Van Crevel, Reinout; van der Ven, Andre Jam
Validated data regarding HIV-transmission in prisons in developing countries is scarce. We examined sexual and injecting drug use behavior and HIV and HCV transmission in an Indonesian narcotic prison during the implementation of an HIV prevention and treatment program during 2004-2007 when the Banceuy Narcotic Prison in Indonesia conducted an HIV transmission prevention program to provide 1) HIV education, 2) voluntary HIV testing and counseling, 3) condom supply, 4) prevention of rape and sexual violence, 5) antiretroviral treatment for HIV-positive prisoners and 6) methadone maintenance treatment. During a first survey that was conducted between 2007 and 2009, new prisoners entered Banceuy Narcotics Prison were voluntary tested for HIV and HCV-infection after written informed consent was obtained. Information regarding sexual and injecting risk behavior and physical status were also recorded at admission to the prison. Participants who tested negative for both HIV and HCV during the first survey were included in a second survey conducted during 2008-2011. During both surveys, data on mortality among HIV-seropositive patients were also recorded. All HIV-seropositive participants receive treatment for HIV. HIV/ AIDS-related deaths decreased: 43% in 2006, 18% in 2007, 9% in 2008 and 0% in 2009. No HIV and HCV seroconversion inside Banceuy Narcotic Prison were found after a median of 23 months imprisonment (maximum follow-up: 38 months). Total of 484.8 person-years observation was done. Participants reported HIV transmission risk-behavior in Banceuy Prison during the second survey was low. After implementation of HIV prevention and treatment program, no new HIV or HCV cases were detected and HIV-related mortality decreased.
Wang, Nanxi; Li, Yue; Niu, Wei; Sun, Ming; Cerny, Ronald; Li, Qingsheng; Guo, Jiantao
A safe and effective vaccine against human immunodeficiency virus type 1 (HIV-1) is urgently needed to combat the worldwide AIDS pandemic, but still remains elusive. The fact that uncontrolled replication of an attenuated vaccine can lead to regaining of its virulence creates safety concerns precluding many vaccines from clinical application. We introduce a novel approach to control HIV-1 replication, which entails the manipulation of essential HIV-1 protein biosynthesis through unnatural amino acid (UAA*)-mediated suppression of genome-encoded blank codon. We successfully demonstrate that HIV-1 replication can be precisely turned on and off in vitro.
Medel-Anonuevo, Carolyn; Cheick, Diarra Mahamadou
This issue in the "Literacy Matters" looks at the relationship between literacy and HIV prevention education. It is the result of the UNESCO Institute for Lifelong Learning's work on examining the contribution of non-formal education (NFE) to HIV prevention, carried out in collaboration with the Association for the Development of…
Mouttapa, Michele; Watson, Donnie W.; McCuller, William J.; Reiber, Chris; Tsai, Winnie
Evidence-based programs for substance use and HIV prevention (SUHIP) were adapted for high-risk juveniles detained at 24-hour secure correctional facilities. In this pilot study, comparisons were made between adolescents who received the SUHIP intervention and a control group on changes in: (1) knowledge of HIV prevention behaviors, (2) attitudes…
LaChausse, Robert G.
This study evaluated the effectiveness of Positive Prevention, a theory-based, HIV/STD prevention education curriculum for high school youth. Three hundred fifty-three students participated in a longitudinal experimental design to determine the impact of the curriculum on HIV/AIDS knowledge, self-efficacy to abstain from sex, self-efficacy of…
Amaro, Hortensia; Raj, Anita; Reed, Elizabeth; Ulibarri, Monica
This article first presents the political, personal, and epidemiological context of Hortensia Amaro's 1988 publication in "Psychology of Women Quarterly" ("PWQ"), "Considerations for Prevention of HIV Infection Among Hispanic Women" (Amaro, 1988). Second, it provides a brief summary of progress in HIV prevention with Latinas. The third section…
Climent, Núria; Assoumou, Lambert; Gil, Cristina; González, Nuria; Alcamí, José; León, Agathe; Romeu, Joan; Dalmau, Judith; Martínez-Picado, Javier; Lifson, Jeff; Autran, Brigitte; Costagliola, Dominique; Clotet, Bonaventura; Gatell, Josep M; Plana, Montserrat; Gallart, Teresa
A double-blinded, controlled study of vaccination of untreated patients with chronic human immunodeficiency virus type 1 (HIV-1) infection with 3 doses of autologous monocyte-derived dendritic cells (MD-DCs) pulsed with heat inactivated autologous HIV-1 was performed. Therapeutic vaccinations were feasible, safe, and well tolerated. At week 24 after first vaccination (primary end point), a modest significant decrease in plasma viral load was observed in vaccine recipients, compared with control subjects (P = .03). In addition, the change in plasma viral load after vaccination tended to be inversely associated with the increase in HIV-specific T cell responses in vaccinated patients but tended to be directly correlated with HIV-specific T cell responses in control subjects. Clinical trial.gov NCT00402142 PMID:21233310
Cohen, Myron S.; Muessig, Kathryn E.; Smith, M. Kumi; Powers, Kimberly A.; Kashuba, Angela D.M.
Antiviral agents can be used to prevent HIV transmission before exposure as preexpo-sure prophylaxis (PrEP), after exposure as postexposure prophylaxis, and as treatment of infected people for secondary prevention. Considerable research has shed new light on antiviral agents for PrEP and for prevention of secondary HIV transmission. While promising results have emerged from several PrEP trials, the challenges of poor adherence among HIV-negative clients and possible increase in sexual risk behaviors remain a concern. In addition, a broader pipeline of antiviral agents for PrEP that focuses on genital tract pharmacology and safety and resistance issues must be developed. Antiretroviral drugs have also been used to prevent HIV transmission from HIV-infected patients to their HIV-discordant sexual partners. The HIV Prevention Trials Network 052 trial demonstrated nearly complete prevention of HIV transmission by early treatment of infection, but the generalizability of the results to other risk groups – including intravenous drug users and MSM – has not been determined. Most importantly, the best strategy for use of antiretroviral agents to reduce the spread of HIV at either the individual level or the population level has not been developed, and remains the ultimate goal of this area of investigation. PMID:22507927
Hales, James R
HIV in Australia was first diagnosed in NSW in the early 1980s, and has had a significant effect on public health. The NSW Government commenced its investment in HIV/AIDS in 1984 and the investment now encompasses research, primary and secondary prevention, and care, treatment and support for people living with HIV/AIDS. A recent study examined the historical impact of the HIV/AIDS epidemic and projected its future impact in NSW. The analysis indicates that the NSW HIV/AIDS investment program has been highly effective in reducing HIV transmission, and has also been cost effective in: avoiding future health-care costs; life years saved; and quality of life benefits. The analysis also indicates that any scaling back of prevention initiatives would result in an increase in the number of people living with HIV.
Protective HIV-1 vaccines would require the induction of broadly neutralizing antibodies (bNAbs) to be effective against the vast diversity of circulating viral strains. Three new studies provide in vivo demonstration that rational design of vaccine strategies using engineered and native-like HIV-1 immunogens can be exploited for guiding B-cell evolution towards the genesis of HIV-1 bNAbs.
The development of a preventive vaccine to neutralize the highly variable and antigenically diverse human immunodeficiency virus type 1 (HIV-1) has been an indomitable goal. The recent discovery of a number of cross-neutralizing and potent monoclonal antibodies from elite neutralizers has provided important insights in this field. Neutralizing antibodies (NAbs) are useful in identifying neutralizing epitopes of vaccine utility and for understanding the mechanism of potent and broad cross-neutralization thus providing a modality of preventive and therapeutic value. In this article we review the current understanding on the potential use of broadly neutralizing antibodies (bNAbs) in their full-length IgG structure, engineered domain antibody or bispecific versions towards preventive and therapeutic applications. The potential implications of NAbs are discussed in the light of the recent developments as key components in vaccination against HIV-1. The development of a vaccine immunogen which elicits bNAbs and confers protective immunity remains a real challenge. PMID:24757516
Harmon, Thomas M.; Fisher, Kevin A.; McGlynn, Margaret G.; Stover, John; Warren, Mitchell J.; Teng, Yu; Näveke, Arne
Background The Investment Framework Enhanced (IFE) proposed in 2013 by the Joint United Nations Programme on HIV/AIDS (UNAIDS) explored how maximizing existing interventions and adding emerging prevention options, including a vaccine, could further reduce new HIV infections and AIDS-related deaths in low- and middle-income countries (LMICs). This article describes additional modeling which looks more closely at the potential health impact and cost-effectiveness of AIDS vaccination in LMICs as part of UNAIDS IFE. Methods An epidemiological model was used to explore the potential impact of AIDS vaccination in LMICs in combination with other interventions through 2070. Assumptions were based on perspectives from research, vaccination and public health experts, as well as observations from other HIV/AIDS interventions and vaccination programs. Sensitivity analyses varied vaccine efficacy, duration of protection, coverage, and cost. Results If UNAIDS IFE goals were fully achieved, new annual HIV infections in LMICs would decline from 2.0 million in 2014 to 550,000 in 2070. A 70% efficacious vaccine introduced in 2027 with three doses, strong uptake and five years of protection would reduce annual new infections by 44% over the first decade, by 65% the first 25 years and by 78% to 122,000 in 2070. Vaccine impact would be much greater if the assumptions in UNAIDS IFE were not fully achieved. An AIDS vaccine would be cost-effective within a wide range of scenarios. Interpretation Even a modestly effective vaccine could contribute strongly to a sustainable response to HIV/AIDS and be cost-effective, even with optimistic assumptions about other interventions. Higher efficacy would provide even greater impact and cost-effectiveness, and would support broader access. Vaccine efficacy and cost per regimen are critical in achieving cost-effectiveness, with cost per regimen being particularly critical in low-income countries and at lower efficacy levels. PMID:26731116
Ching, Michael SL
Japan is well known as a country with a strong health record. However its incidence rates of vaccine preventable diseases (VPD) such as hepatitis B, measles, mumps, rubella, and varicella remain higher than other developed countries. This article reviews the factors that contribute to the high rates of VPD in Japan. These include historical and political factors that delayed the introduction of several important vaccines until recently. Access has also been affected by vaccines being divided into government-funded “routine” (eg, polio, pertussis) and self-pay “voluntary” groups (eg, hepatitis A and B). Routine vaccines have higher rates of administration than voluntary vaccines. Administration factors include differences in well child care schedules, the approach to simultaneous vaccination, vaccination contraindication due to fever, and vaccination spacing. Parental factors include low intention to fully vaccinate their children and misperceptions about side effects and efficacy. There are also provider knowledge gaps regarding indications, adverse effects, interval, and simultaneous vaccination. These multifactorial issues combine to produce lower population immunization rates and a higher incidence of VPD than other developed countries. This article will provide insight into the current situation of Japanese vaccinations, the issues to be addressed and suggestions for public health promotion. PMID:25628969
Bliss, Sandra J; O'Brien, Katherine L; Janoff, Edward N; Cotton, Mark F; Musoke, Philippa; Coovadia, Hoosen; Levine, Orin S
Pneumococcal conjugate vaccines (PCVs) are a potentially useful complement to existing treatment strategies in HIV-infected children, for whom pneumococcal infections are common and serious. This Review summarises available data on the burden of pneumococcal disease and the safety and efficacy of PCVs in HIV-infected children. The data demonstrate that children with HIV have significantly increased risk of pneumococcal disease compared with uninfected children; the serotypes included in currently licensed or near-licensure conjugate vaccines include most serotypes that cause invasive pneumococcal disease (IPD) in HIV-infected children and adults; PCVs provide substantial protection against IPD and clinical pneumonia when given to HIV-infected infants; and HIV-infected adults gain an indirect benefit when children in the community are vaccinated. PCV should be considered as an important intervention for improving the lives of HIV-infected children.
Patterson, L. Jean; Robert-Guroff, Marjorie
Background In the last few years the HIV vaccine field has moved forward a number of promising vaccine candidates into human clinical trials. Objective In this review we briefly discuss the advances made in vaccine development and HIV pathogenesis and give an overview of the body of work our lab has generated in multiple animal models on replication-competent Ad recombinant vaccines. Methods Emphasis is placed on comparative examination of vaccine components, routes of immunization and challenge models using replicating Ad vectors. Results/conclusion The overall findings make the case that replicating Ad vectors are superior in priming multiple arms of the immune system, and in conjunction with protein boosting, have resulted in dramatic protective efficacy leading to their advancement to phase 1 trials. Implications of the recent halting of the Merck Ad5-HIV phase 2b clinical trial for our vaccine approach and other vectored vaccines are discussed. PMID:18694354
Hayami, Masanori; Horiuchi, Reii
A great effort for developing AIDS vaccine has been carried out in the world, designed by various new ideas based on basic research information obtained in recent virology and immunology. Withall it, to obtain effective AIDS vaccine is considered skeptical. One of the reasons of its difficulty is a lack of experimental animals susceptible to HIV-1. In our laboratory, we have succeeded in developing chimeric SIV having 3' half of HIV-1 genome including env (SHIV), which is infectious to macaque monkeys. One of SHIVs has been proved nonpathogenic in monkeys from various aspects and it afforded protective immunity to monkeys against pathogenic SHIV challenge infection. Now, we are trying to develop anti-HIV live attenuated vaccines using the nonpathogenic SHIV as a starting material. In the history of virus vaccine, live attenuated vaccines have been proved most effective in measles and polio-myelitis. However, it is not clear whether nonpathogenic HIV exists or not. Futhermore, even if nonpathogenic HIV could be obtained, there is possibility that it will easily mutate to pathogenic one. Therefore, to develop live attenuated AIDS vaccine is considered dangerous. In this article, We will introduce our research on SHIV pathogenicity using monkeys and hypothesize possibility to obtain nonpathogenic HIV which is speculated from the origin and evolution of HIV/SIV. To clarify virulence and nonvirulence of HIV and to obtain nonpathogenic virus are not only applied research but also basic science to dissolve the fundemental question why HIV can induce the disease.
Le Grand, Roger; Dereuddre-Bosquet, Nathalie; Dispinseri, Stefania; Gosse, Leslie; Desjardins, Delphine; Shen, Xiaoying; Tolazzi, Monica; Ochsenbauer, Christina; Saidi, Hela; Tomaras, Georgia; Prague, Mélanie; Barnett, Susan W.; Thiebaut, Rodolphe; Scarlatti, Gabriella
ABSTRACT Although vaccines and antiretroviral (ARV) prevention have demonstrated partial success against human immunodeficiency virus (HIV) infection in clinical trials, their combined introduction could provide more potent protection. Furthermore, combination approaches could ameliorate the potential increased risk of infection following vaccination in the absence of protective immunity. We used a nonhuman primate model to determine potential interactions of combining a partially effective ARV microbicide with an envelope-based vaccine. The vaccine alone provided no protection from infection following 12 consecutive low-dose intravaginal challenges with simian-HIV strain SF162P3, with more animals infected compared to naive controls. The microbicide alone provided a 68% reduction in the risk of infection relative to that of the vaccine group and a 45% reduction relative to that of naive controls. The vaccine-microbicide combination provided an 88% reduction in the per-exposure risk of infection relative to the vaccine alone and a 79% reduction relative to that of the controls. Protected animals in the vaccine-microbicide group were challenged a further 12 times in the absence of microbicide and demonstrated a 98% reduction in the risk of infection. A total risk reduction of 91% was observed in this group over 24 exposures (P = 0.004). These important findings suggest that combined implementation of new biomedical prevention strategies may provide significant gains in HIV prevention. IMPORTANCE There is a pressing need to maximize the impact of new biomedical prevention tools in the face of the 2 million HIV infections that occur each year. Combined implementation of complementary biomedical approaches could create additive or synergistic effects that drive improved reduction of HIV incidence. Therefore, we assessed a combination of an untested vaccine with an ARV-based microbicide in a nonhuman primate vaginal challenge model. The vaccine alone provided no
McDavitt, Bryce; Ghani, Mansur A.; Nogg, Kelsey; Winder, Terrell J.A.; Soto, Juliana K.
Abstract Biomedical HIV prevention strategies, such as pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP), represent new opportunities to reduce critically high HIV infection rates among young black men who have sex with men (YBMSM). We report results of 24 dyadic qualitative interviews (N=48), conducted in Los Angeles, CA, exploring how YBMSM and their friends view PrEP and PEP. Interviews were analyzed using a grounded theory approach. Participants had widely divergent levels of knowledge about these prevention methods. Misconceptions and mistrust regarding PrEP were common, and concerns were expressed about PrEP-related stigma and the potential for gossip among peers who might assume a person on PrEP was HIV-positive. Yet participants also framed PrEP and PEP as valuable new options within an expanded “tool kit” of HIV prevention strategies that created possibilities for preventing new HIV infections, dating men with a different HIV status, and decreased anxiety about exposure to HIV. We organized themes around four main areas: (1) information and misinformation about biomedical HIV prevention; (2) expectations about PrEP, sexual behavior, and stigma; (3) gossip, disclosure, and “spreading the word” about PrEP and PEP; and (4) the roles of PrEP and PEP in an expanded HIV prevention tool kit. The findings suggest a need for guidance in navigating the increasingly complex array of HIV-prevention options available to YBMSM. Such “prevention navigation” could counter misconceptions and address barriers, such as stigma and mistrust, while helping YBMSM make informed selections from among expanded HIV prevention options. PMID:26121564
Cianelli, Rosina; Ferrer, Lilian; McElmurry, Beverly J
Socio-cultural factors and HIV-related misinformation contribute to the increasing number of Chilean women living with HIV. In spite of this, and to date, few culturally specific prevention activities have been developed for this population. The goal of the present study was to elicit the perspectives of low-income Chilean women regarding HIV and relevant socio-cultural factors, as a forerunner to the development of a culturally appropriate intervention. As part of a mixed-methods study, fifty low-income Chilean women participated in a survey and twenty were selected to participate in prevention, in-depth interviews. Results show evidence of widespread misinformation and misconceptions related to HIV/AIDS. Machismo and marianismo offer major barriers to prevention programme development. Future HIV prevention should stress partner communication, empowerment and improving the education of women vulnerable to HIV.
Stephenson, Kathryn E.; Neubauer, George H.; Reimer, Ulf; ...
An effective vaccine against human immunodeficiency virus type 1 (HIV-1) will have to provide protection against a vast array of different HIV-1 strains. Current methods to measure HIV-1-specific binding antibodies following immunization typically focus on determining the magnitude of antibody responses, but the epitope diversity of antibody responses has remained largely unexplored. Here we describe the development of a global HIV-1 peptide microarray that contains 6564 peptides from across the HIV-1 proteome and covers the majority of HIV-1 sequences in the Los Alamos National Laboratory global HIV-1 sequence database. Using this microarray, we quantified the magnitude, breadth, and depth ofmore » IgG binding to linear HIV-1 sequences in HIV-1-infected humans and HIV-1-vaccinated humans, rhesus monkeys and guinea pigs. The microarray measured potentially important differences in antibody epitope diversity, particularly regarding the depth of epitope variants recognized at each binding site. Our data suggest that the global HIV-1 peptide microarray may be a useful tool for both preclinical and clinical HIV-1 research.« less
Stephenson, Kathryn E.; Neubauer, George H.; Reimer, Ulf; Pawlowski, Nikolaus; Knaute, Tobias; Zerweck, Johannes; Korber, Bette T.; Barouch, Dan H.
An effective vaccine against human immunodeficiency virus type 1 (HIV-1) will have to provide protection against a vast array of different HIV-1 strains. Current methods to measure HIV-1-specific binding antibodies following immunization typically focus on determining the magnitude of antibody responses, but the epitope diversity of antibody responses has remained largely unexplored. Here we describe the development of a global HIV-1 peptide microarray that contains 6564 peptides from across the HIV-1 proteome and covers the majority of HIV-1 sequences in the Los Alamos National Laboratory global HIV-1 sequence database. Using this microarray, we quantified the magnitude, breadth, and depth of IgG binding to linear HIV-1 sequences in HIV-1-infected humans and HIV-1-vaccinated humans, rhesus monkeys and guinea pigs. The microarray measured potentially important differences in antibody epitope diversity, particularly regarding the depth of epitope variants recognized at each binding site. Our data suggest that the global HIV-1 peptide microarray may be a useful tool for both preclinical and clinical HIV-1 research.
Sanders, Rogier W; van Gils, Marit J; Derking, Ronald; Sok, Devin; Ketas, Thomas J; Burger, Judith A; Ozorowski, Gabriel; Cupo, Albert; Simonich, Cassandra; Goo, Leslie; Arendt, Heather; Kim, Helen J; Lee, Jeong Hyun; Pugach, Pavel; Williams, Melissa; Debnath, Gargi; Moldt, Brian; van Breemen, Mariëlle J; Isik, Gözde; Medina-Ramírez, Max; Back, Jaap Willem; Koff, Wayne C; Julien, Jean-Philippe; Rakasz, Eva G; Seaman, Michael S; Guttman, Miklos; Lee, Kelly K; Klasse, Per Johan; LaBranche, Celia; Schief, William R; Wilson, Ian A; Overbaugh, Julie; Burton, Dennis R; Ward, Andrew B; Montefiori, David C; Dean, Hansi; Moore, John P
A challenge for HIV-1 immunogen design is the difficulty of inducing neutralizing antibodies (NAbs) against neutralization-resistant (tier 2) viruses that dominate human transmissions. We show that a soluble recombinant HIV-1 envelope glycoprotein trimer that adopts a native conformation, BG505 SOSIP.664, induced NAbs potently against the sequence-matched tier 2 virus in rabbits and similar but weaker responses in macaques. The trimer also consistently induced cross-reactive NAbs against more sensitive (tier 1) viruses. Tier 2 NAbs recognized conformational epitopes that differed between animals and in some cases overlapped with those recognized by broadly neutralizing antibodies (bNAbs), whereas tier 1 responses targeted linear V3 epitopes. A second trimer, B41 SOSIP.664, also induced a strong autologous tier 2 NAb response in rabbits. Thus, native-like trimers represent a promising starting point for the development of HIV-1 vaccines aimed at inducing bNAbs.
Öbrink-Hansen, Kristina; Søgaard, Ole S; Harboe, Zitta B; Schønheyder, Henrik C
HIV-infected individuals have excess rates of invasive pneumococcal disease. We investigated risk factors for nasopharyngeal pneumococcal colonization at baseline and after 9 months in 96 HIV patients immunized twice with 7- valent pneumococcal conjugate vaccine ±1mg CPG 7909. In total, 22 patients (23%) were colonized, 11 at baseline only, four at both baseline and 9 months, and seven at 9 months only. Compared to non-colonized patients, more colonized patients were smokers, had lower CD4+ nadir and had an AIDS-diagnosis. Immunization, antiretroviral treatment and the CPG adjuvant had no impact on colonization. These results suggest preventive strategies in addition to pneumococcal immunization.
O'Dell, Brennan L; Rosser, B R Simon; Miner, Michael H; Jacoby, Scott M
An understanding of men's motivations to avoid risk behavior is needed to create efficacious HIV prevention programs for HIV-positive men who have sex with men (MSM). This study investigates the relationship between sexual risk behavior and HIV prevention altruism, which is defined as the values, motivations, and practices of caretaking towards one's sexual partners to prevent the transmission of HIV. In a sample of 637 HIV-positive MSM, HIV prevention altruism significantly protects against serodiscordant unprotected anal intercourse (SDUAI) in crude analysis, but not after adjustment for drug use and compulsive sexual behavior. HIV prevention altruism is also related to not engaging in anal intercourse, but is not related to serodisclosure to secondary partners. Lack of altruism appears related to sexual risk behavior in HIV-positive MSM, although other psychological and contextual factors play significant roles. The promotion of HIV prevention altruism may provide a formidable new direction for HIV prevention programs.
Brady, Jacqueline M; Baltimore, David; Balazs, Alejandro B
Broadly neutralizing antibodies (bNAbs) against human immunodeficiency virus (HIV) show great promise in HIV prevention as they are capable of potently neutralizing a considerable breadth of genetically diverse strains. Passive transfer of monoclonal bNAb proteins can confer protection in animal models of HIV infection at modest concentrations, inspiring efforts to develop an HIV vaccine capable of eliciting bNAb responses. However, these antibodies demonstrate high degrees of somatic mutation and other unique characteristics that may hinder the ability of conventional approaches to consistently and effectively produce bNAb analogs. As an alternative strategy, we and others have proposed vector-mediated gene transfer to generate long-term, systemic production of bNAbs in the absence of immunization. Herein, we review the use of adeno-associated virus (AAV) vectors for delivery of HIV bNAbs and antibody-like proteins and summarize both the advantages and disadvantages of this strategy as a method for HIV prevention.
Yao, Zhi Q.; Moorman, Jonathan P.
Given the shared risk factors for transmission, co-infection of hepatitis B virus (HBV) with hepatitis C virus (HCV) and/or human immunodeficiency virus (HIV) is quite common, and may lead to increases in morbidity and mortality. As such, HBV vaccine is recommended as the primary means to prevent HBV super-infection in HCV- and/or HIV-infected individuals. However, vaccine response (sero-conversion with a hepatitis B surface antibody titer >10 IU/L) in this setting is often blunted, with poor response rates to standard HBV vaccinations in virally infected individuals when compared to the healthy subjects. This phenomenon also occurs to other vaccines in adults, such as pneumococcal and influenza vaccines, in other immunocompromised hosts who are really at risk for opportunistic infections, such as individuals with hemodialysis, transplant, and malignancy. In this review, we summarize the underlying mechanisms involving vaccine failure in these conditions, focusing on immune exhaustion and immune senescence - two distinct signaling pathways regulating cell function and fate. We raise the possibility that blocking these negative signaling pathways might improve success rates of immunizations in the setting of chronic viral infection. PMID:23400275
Kuo, Caroline; Atujuna, Millicent; Mathews, Catherine; Stein, Dan J.; Hoare, Jacqueline; Beardslee, William; Operario, Don; Cluver, Lucie; K. Brown, Larry
ABSTRACT Adolescents and young people account for 40% of all new HIV infections each year, with South Africa one of the hardest hit countries, and having the largest population of people living with HIV. Although adolescent HIV prevention has been delivered through diverse modalities in South Africa, and although family-based approaches for adolescent HIV prevention have great potential for highly affected settings such as South Africa, there is a scarcity of empirically tested family-based adolescent HIV preventive interventions in this setting. We therefore conducted focus groups and in-depth interviews with key informants including clinicians, researchers, and other individuals representing organizations providing HIV and related health services to adolescents and parents (N = 82). We explored family perspectives and interactions around topics such as communication about sex, HIV, and relationships. Participants described aspects of family interactions that presented both challenges and opportunities for family-based adolescent HIV prevention. Parent–child communication on sexual topics were taboo, with these conversations perceived by some adults as an invitation for children to engage in HIV risk behavior. Parents experienced social sanctions for discussing sex and adolescents who asked about sex were often viewed as disrespectful and needing discipline. However, participants also identified context-appropriate strategies for addressing family challenges around HIV prevention including family meetings, communal parenting, building efficacy around parent–adolescent communication around sexual topics, and the need to strengthen family bonding and positive parenting. Findings indicate the need for a family intervention and identify strategies for development of family-based interventions for adolescent HIV prevention. These findings will inform design of a family intervention to be tested in a randomized pilot trial (ClinicalTrials.gov #NCT02432352). PMID
Kuo, Caroline; Atujuna, Millicent; Mathews, Catherine; Stein, Dan J; Hoare, Jacqueline; Beardslee, William; Operario, Don; Cluver, Lucie; K Brown, Larry
Adolescents and young people account for 40% of all new HIV infections each year, with South Africa one of the hardest hit countries, and having the largest population of people living with HIV. Although adolescent HIV prevention has been delivered through diverse modalities in South Africa, and although family-based approaches for adolescent HIV prevention have great potential for highly affected settings such as South Africa, there is a scarcity of empirically tested family-based adolescent HIV preventive interventions in this setting. We therefore conducted focus groups and in-depth interviews with key informants including clinicians, researchers, and other individuals representing organizations providing HIV and related health services to adolescents and parents (N = 82). We explored family perspectives and interactions around topics such as communication about sex, HIV, and relationships. Participants described aspects of family interactions that presented both challenges and opportunities for family-based adolescent HIV prevention. Parent-child communication on sexual topics were taboo, with these conversations perceived by some adults as an invitation for children to engage in HIV risk behavior. Parents experienced social sanctions for discussing sex and adolescents who asked about sex were often viewed as disrespectful and needing discipline. However, participants also identified context-appropriate strategies for addressing family challenges around HIV prevention including family meetings, communal parenting, building efficacy around parent-adolescent communication around sexual topics, and the need to strengthen family bonding and positive parenting. Findings indicate the need for a family intervention and identify strategies for development of family-based interventions for adolescent HIV prevention. These findings will inform design of a family intervention to be tested in a randomized pilot trial (ClinicalTrials.gov #NCT02432352).
Mitchell, Jason W.
The majority of HIV prevention studies and programs have targeted individuals or operated at the community level. This has also been the standard approach when incorporating technology (e.g., web-based, smartphones) to help improve HIV prevention efforts. The tides have turned for both approaches: greater attention is now focusing on couples-based HIV prevention and using technology to help improve these efforts for maximizing reach and potential impact. To assess the extent that technology has been used to help advance HIV prevention with couples, a literature review was conducted using four databases and included studies that collected data from 2000 to early 2015. Results from this review suggest technology has primarily been used to help advance HIV prevention with couples as a tool for 1) recruitment and data collection and 2) intervention development. Challenges and limitations of conducting research (e.g., validity of dyadic data) along with future directions for how technology (e.g. mHealth, wearable sensors) can be used to advance HIV prevention with couples are then discussed. Given the growing and near ubiquitous use of the Internet and smartphones, further efforts in the realm of mhealth (e.g., applications or “apps”) and eHealth are needed to develop novel couples-focused HIV preventive interventions. PMID:26412083
Ivers, Louise C; Charles, Richelle C; Hilaire, Isabelle J; Mayo-Smith, Leslie M; Teng, Jessica E; Jerome, J Gregory; Rychert, Jenna; LaRocque, Regina C; Xu, Peng; Kovácˇ, Pavol; Ryan, Edward T; Qadri, Firdausi; Almazor, Charles P; Franke, Molly F; Harris, Jason B
We evaluated immune responses following bivalent oral cholera vaccination (Shanchol [Shantha Biotechnics]; BivWC) in a cohort of 25 human immunodeficiency virus (HIV)-infected adults in Haiti. Compared with adults without HIV infection, vaccination in HIV-infected individuals resulted in lower vibriocidal responses against Vibrio cholerae O1, and there was a positive relationship between the CD4(+) T-cell count and vibriocidal responses following vaccination. Nevertheless, seroconversion occurred at a rate of 65% against the Ogawa serotype and 74% against the Inaba serotype in adults with HIV infection. These results suggest that the vaccine retains substantial immunogenicity in adults with HIV infection and may benefit this population by protecting against cholera.
Cameron, Michael P; Newman, Peter A; Roungprakhon, Surachet; Scarpa, Riccardo
This paper estimates the marginal willingness-to-pay for attributes of a hypothetical HIV vaccine using discrete choice modeling. We use primary data from 326 respondents from Bangkok and Chiang Mai, Thailand, in 2008-2009, selected using purposive, venue-based sampling across two strata. Participants completed a structured questionnaire and full rank discrete choice modeling task administered using computer-assisted personal interviewing. The choice experiment was used to rank eight hypothetical HIV vaccine scenarios, with each scenario comprising seven attributes (including cost) each of which had two levels. The data were analyzed in two alternative specifications: (1) best-worst; and (2) full-rank, using logit likelihood functions estimated with custom routines in Gauss matrix programming language. In the full-rank specification, all vaccine attributes are significant predictors of probability of vaccine choice. The biomedical attributes of the hypothetical HIV vaccine (efficacy, absence of VISP, absence of side effects, and duration of effect) are the most important attributes for HIV vaccine choice. On average respondents are more than twice as likely to accept a vaccine with 99% efficacy, than a vaccine with 50% efficacy. This translates to a willingness to pay US$383 more for a high efficacy vaccine compared with the low efficacy vaccine. Knowledge of the relative importance of determinants of HIV vaccine acceptability is important to ensure the success of future vaccination programs. Future acceptability studies of hypothetical HIV vaccines should use more finely grained biomedical attributes, and could also improve the external validity of results by including more levels of the cost attribute.
Dudani, A K; Martyres, A; Fliss, H
A current urgent priority is to develop microbicides and vaccines to combat retroviruses like human immunodeficiency virus (HIV). We show that the cysteine-selective natural compound, taurine chloramine (T-NCl), can be effective in this task. A number of proteins in all retroviruses contain highly conserved cysteine-rich regions that are essential for infection and replication. Our data show that by targeting these essential cysteine residues, T-NCl (2 or 5 mM) acts as a highly effective and safe microbicide that fully blocks the infectivity of high HIV-1 titers (10(6) TCID(50) units/ml) but is not injurious to eukaryotic cells. We also demonstrate that T-NCl can be used to prepare a highly effective whole-killed vaccine against murine AIDS (MAIDS) that shows both preventive and therapeutic efficacy. The vaccine consists of a T-NCl-inactivated retrovirus suspension in host cell lysate. The novelty of our approach lies in the ease and speed of vaccine preparation and its avoidance of harsh inactivation or purification steps that can alter native viral conformation. Our approach is therefore likely to overcome a number of intractable obstacles to the preparation of an effective whole-killed HIV vaccine, such as surviving infective viral particles, rapid viral mutation rates, numerous viral strains, and harsh purification steps. Our approach may also permit the rapid preparation of autologous, or custom-made, vaccines for individual patients.
Lee, Kuan-Yeh; Tsai, Mao-Song; Kuo, Kuang-Che; Tsai, Jen-Chih; Sun, Hsin-Yun; Cheng, Aristine C; Chang, Sui-Yuan; Lee, Chen-Hsiang; Hung, Chien-Ching
HIV-infected patients remain at higher risk for pneumococcal disease than the general population despite immune reconstitution and suppression of HIV replication with combination antiretroviral therapy. Vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23) composed of T-cell-independent antigens has been recommended to reduce the risk of pneumococcal disease in HIV-infected adults. However, given the heterogeneity of study design, execution and subjects enrolled, studies examining serological responses to PPV23 yielded conflicting results and observational studies of clinical effectiveness only provided moderate evidence to support the routine use of PPV23 in HIV-infected adults. Pneumococcal conjugate vaccine (PCV), with conjugation of the capsular polysaccharide to a protein carrier, is more immunogenic than PPV23 and has been demonstrated to protect against pneumococcal disease in HIV-infected children and recurrent invasive pneumococcal disease in HIV-infected adolescents and adults. Guidelines have recently been revised to recommend that HIV-infected patients aged 19 y or older receive one dose of 13-valent pneumococcal conjugate vaccine (PCV13) followed by a booster vaccination with PPV23. In this paper, we review the studies using different vaccination strategies to improve immunogenicity among HIV-infected adult patients. PMID:25483681
Lippman, Sheri A.; Maman, Suzanne; MacPhail, Catherine; Twine, Rhian; Peacock, Dean; Kahn, Kathleen; Pettifor, Audrey
Introduction Community mobilizing strategies are essential to health promotion and uptake of HIV prevention. However, there has been little conceptual work conducted to establish the core components of community mobilization, which are needed to guide HIV prevention programming and evaluation. Objectives We aimed to identify the key domains of community mobilization (CM) essential to change health outcomes or behaviors, and to determine whether these hypothesized CM domains were relevant to a rural South African setting. Method We studied social movements and community capacity, empowerment and development literatures, assessing common elements needed to operationalize HIV programs at a community level. After synthesizing these elements into six essential CM domains, we explored the salience of these CM domains qualitatively, through analysis of 10 key informant in-depth-interviews and seven focus groups in three villages in Bushbuckridge. Results CM domains include: 1) shared concerns, 2) critical consciousness, 3) organizational structures/networks, 4) leadership (individual and/or institutional), 5) collective activities/actions, and 6) social cohesion. Qualitative data indicated that the proposed domains tapped into theoretically consistent constructs comprising aspects of CM processes. Some domains, extracted from largely Western theory, required little adaptation for the South African context; others translated less effortlessly. For example, critical consciousness to collectively question and resolve community challenges functioned as expected. However, organizations/networks, while essential, operated differently than originally hypothesized - not through formal organizations, but through diffuse family networks. Conclusions To date, few community mobilizing efforts in HIV prevention have clearly defined the meaning and domains of CM prior to intervention design. We distilled six CM domains from the literature; all were pertinent to mobilization in rural
Quinn, K J; McCarty, E J; Quah, S P; Emerson, C R; Donnelly, C M
The British HIV Association (BHIVA) has published guidelines for immunization of HIV-infected adults. A chart review of 200 HIV-infected patients diagnosed was conducted to determine shortcomings in previous practice and determine which vaccines should routinely be given in specialist HIV clinics and which might be able to be delegated to primary care clinics. Data were collected on administration of three categories of vaccinations: (1) vaccines used in all individuals with chronic disease (pneumococcal, influenza, swine flu H1N1); (2) targeted vaccinations used in non-immune individuals with HIV who are at risk of exposure (hepatitis A and hepatitis B); (3) routine vaccines traditionally delivered to the whole population (measles/mumps/rubella [MMR], diphtheria/tetanus/pertussis and meningitis C/ACWY). Pneumococcal vaccine was delivered to 54% of eligible patients, 52% of eligible individuals completed a full hepatitis B programme of vaccination and 21% (42/200) were naturally immune; hepatitis A vaccine was delivered to 36% of eligible individuals. With increasing demands on resources, it seems likely that HIV services will have to harness resources of primary care in vaccine programmes in relation to routine vaccines. By improving communication between primary and secondary care mistakes with live vaccination decisions could be avoided; HIV services should continue to perform targeted and chronic disease vaccines, i.e. for category 1 and category 2 vaccines.
de Arístegui Fernández, J; Corretger Rauet, J M; García Martín, F; Hernández-Sampelayo, T; Moraga Llop, F A; Rodrigo Gonzalo De Liria, C; Ruiz Contreras, J
Pneumococcal disease is a major cause of morbidity, hospitalization and mortality. Two age groups show a greater incidence and severity of the disease: children under the age of 5 years (mainly during the first 2 years of life) and adults aged more than 65 years. The heptavalent pneumococcal conjugate vaccine, which was commercialized in Spain in June 2001, is efficacious in children aged less than 2 years and, unlike the non-conjugate 23-valent vaccine, it induces immunological memory. In Spain the heptavalent vaccine covers 80 % of serotypes causing pneumococcal invasive disease and acute otitis media in children aged 2-59 months. The heptavalent vaccine has been shown to be immunogenic, efficacious and safe. It has proven efficacy in the prevention of invasive disease caused by the seven vaccine serotypes. In addition, it significantly decreases pneumonia and also prevent acute otitis media. The vaccine is preferably indicated in children aged less than 2 years; children aged 2-5 years may also benefit from the vaccine but those in risk groups should be prioritized. Greater knowledge of the epidemiology of pneumococcal disease and the efficiency of this vaccine in Spain will determine whether it should be included in the immunization schedule.
The evidence that high-risk HPV infections cause cervical cancers has led to two new approaches for cervical cancer control: vaccination to prevent HPV infections, and HPV screening to detect and treat cervical precancerous lesions. Two vaccines are currently available: quadrivalent vaccine targeting oncogenic HPV types 16, 18, 6, and 11, and bivalent vaccine targeting HPV 16 and 18. Both vaccines have demonstrated remarkable immunogenicity and substantial protection against persistent infection and high-grade cervical cancer precursors caused by HPV 16 and 18 in HPV-naïve women, and have the potential to prevent 70% of cervical cancers in adequately vaccinated populations. HPV vaccination is now implemented in national programs in 62 countries, including some low- and middle-income countries. The early findings from routine national programs in high-income countries are instructive to encourage low- and middle-income countries with a high risk of cervical cancer to roll out HPV vaccination programs and to introduce resource-appropriate cervical screening programs.
Kourkounti, Sofia; Paparizos, Vassilios; Leuow, Kirsten; Paparizou, Eleni; Antoniou, Christina
Although vaccination against hepatitis A virus (HAV) is essential for human immunodeficiency virus (HIV)-infected patients, the uptake of HAV vaccine is reported to be very low. From 2007 to 2012, 912 HIV-infected men in Athens, Greece were screened for exposure to HAV. Two doses of an HAV vaccine were recommended to 569 eligible patients. Reminder cards with scheduled vaccination visits were given to each patient. Among eligible patients, 62.2% (354/569) received both doses. Patients who were fully vaccinated compared with non-adherent patients were natives, older, had undetectable HIV viral load, higher CD4 T cell counts and lower nadir CD4 T cell counts. Multivariate logistic regression revealed that the patient's country of origin (p = 0.024; OR = 2.712; 95% CI, 1.139-6.457), CD4 T cell count (p < 0.001) and nadir CD4 T cell count (p < 0.001) were factors directly associated with adherence. In conclusion, adherence to HAV vaccination was better than in previously published data. Because many of the factors related to vaccination completion are parameters of HIV infection, it appears that physician interest in HIV care and vaccination planning is crucial to enhancing vaccine uptake.
Vargas-Inchaustegui, Diego A; Robert-Guroff, Marjorie
The modest success of the RV144 HIV vaccine trial in Thailand and the ensuing suggestion that a Fc-receptormediated antibody activity might have played a role in the protection observed have intensified investigations on Fcrelated immune responses. HIV neutralizing antibodies have been and continue to be the focal point of research into humoral immune protection. However, recent knowledge that their protective efficacy can be augmented by Fc-FcR interactions has increased the complexity of identifying immune correlates of protection. If anything, continued studies of both humoral and cellular immune mechanisms point to the lack of a single protective anti-HIV immune response. Here we focus on humoral immunity, analyzing the role played by Fc receptor-related responses and discussing how new knowledge of their interactions requires further investigation, but may also spur novel vaccination approaches. We initially address classical Fc-receptor mediated anti-viral mechanisms including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cell mediated viral inhibition (ADCVI), and antibody-dependent cellular phagocytosis (ADCP), as well as the effector cells that mediate these functions. Next, we summarize key aspects of FcR-Fc interactions that are important for potential control of HIV/SIV such as FcR polymorphisms and post-transcriptional modifications. Finally we discuss less commonly studied non-mechanistic anti-HIV immune functions: antibody avidity and envelopespecific B cell memory. Overall, a spectrum of immune responses, reflecting the immune system's redundancy, will likely be needed to prevent HIV infection and/or disease progression. Aside from elicitation of critical immune mechanisms, a successful vaccine will need to induce mature B cell responses and long-lasting immune memory.
AIDS Drug Assistance Programs in several states already have to put HIV-infected people on waiting lists to receive life-saving antiretroviral drugs because of budget shortfalls, and AIDS advocates say this problem will continue through 2002 and 2003 unless Congress provides a financial boost to HIV programs. Activists also say the United States will never achieve its goal of reducing new HIV infection rates by 50% within the next few years unless prevention spending is increased.
Solorio, Rosa; Norton-Shelpuk, Pamela; Forehand, Mark; Martinez, Marcos; Aguirre, Joel
Young Latino immigrant men who have sex with men (MSM) are at risk for HIV and for delayed diagnosis. A need exists to raise awareness about HIV prevention in this population, including the benefits of timely HIV testing. This project was developed through collaboration between University of WA researchers and Entre Hermanos, a community-based organization serving Latinos. Building from a community-based participatory research approach, the researchers developed a campaign that was executed by Activate Brands, based in Denver, Colorado. The authors (a) describe the development of HIV prevention messages through the integration of previously collected formative data; (b) describe the process of translating these messages into PSAs, including the application of a marketing strategy; (c) describe testing the PSAs within the Latino MSM community; and (c) determine a set of important factors to consider when developing HIV prevention messages for young Latino MSM who do not identify as gay.
Tsai, Alexander C.
Renewed enthusiasm for biomedical HIV prevention strategies has followed the recent publication of several high-profile HIV antiretroviral therapy-based HIV prevention trials. In a recent article, Roberts & Matthews (2012) accurately note some of the shortcomings of these individually targeted approaches to HIV prevention and advocate for increased emphasis on structural interventions that have more fundamental effects on the population distribution of HIV. However, they make some implicit assumptions about the extent to which structural interventions are user-independent and more sustainable than biomedical or behavioral interventions. In this article, I elaborate a simple typology of structural interventions along these two axes and suggest that they may be neither user-independent nor sustainable and therefore subject to the same sustainability concerns, costs, and potential unintended consequences as biomedical and behavioral interventions. PMID:22877933
Solorio, Rosa; Forehand, Mark; Aguirre, Joel
Young Latino immigrant men who have sex with men (MSM) are at risk for HIV and for delayed diagnosis. A need exists to raise awareness about HIV prevention in this population, including the benefits of timely HIV testing. This project was developed through collaboration between University of WA researchers and Entre Hermanos, a community-based organization serving Latinos. Building from a community-based participatory research approach, the researchers developed a campaign that was executed by Activate Brands, based in Denver, Colorado. The authors (a) describe the development of HIV prevention messages through the integration of previously collected formative data; (b) describe the process of translating these messages into PSAs, including the application of a marketing strategy; (c) describe testing the PSAs within the Latino MSM community; and (c) determine a set of important factors to consider when developing HIV prevention messages for young Latino MSM who do not identify as gay. PMID:24864201
Poteat, Tonia; Wirtz, Andrea L; Radix, Anita; Borquez, Annick; Silva-Santisteban, Alfonso; Deutsch, Madeline B; Khan, Sharful Islam; Winter, Sam; Operario, Don
Worldwide, transgender women who engage in sex work have a disproportionate risk for HIV compared with natal male and female sex workers. We reviewed recent epidemiological research on HIV in transgender women and show that transgender women sex workers (TSW) face unique structural, interpersonal, and individual vulnerabilities that contribute to risk for HIV. Only six studies of evidence-based prevention interventions were identified, none of which focused exclusively on TSW. We developed a deterministic model based on findings related to HIV risks and interventions. The model examines HIV prevention approaches in TSW in two settings (Lima, Peru and San Francisco, CA, USA) to identify which interventions would probably achieve the UN goal of 50% reduction in HIV incidence in 10 years. A combination of interventions that achieves small changes in behaviour and low coverage of biomedical interventions was promising in both settings, suggesting that the expansion of prevention services in TSW would be highly effective. However, this expansion needs appropriate sustainable interventions to tackle the upstream drivers of HIV risk and successfully reach this population. Case studies of six countries show context-specific issues that should inform development and implementation of key interventions across heterogeneous settings. We summarise the evidence and knowledge gaps that affect the HIV epidemic in TSW, and propose a research agenda to improve HIV services and policies for this population. PMID:25059941
Sun, Jing; Hou, Jue; Li, Dingfeng; Liu, Yong; Hu, Ningzhu; Hao, Yanling; Fu, Jingjing; Hu, Yunzhang; Shao, Yiming
Although the importance of DNA vaccines, especially as a priming immunization has been well established in numerous HIV vaccine studies, the immunogenictiy of DNA vaccines is generally moderate. Novel adjuvant is in urgent need for improving the immunogenicity of DNA vaccine. Polysaccharide and nucleic acid fraction extracted by hot phenol method from Mycobacterium bovis bacillus Calmette-Guérin, known as BCG-PSN, is a widely used immunomodulatory product in China clinical practice. In this study, we evaluated whether the BCG-PSN could serve as a novel adjuvant of DNA vaccine to trigger better cellular and humoral immune responses against the HIV-1 Env antigen in Balb/C mouse model. The BCG-PSN was mixed with 10 μg or 100 μg of pDRVI1.0gp145 (HIV-1 CN54 gp145 gene) DNA vaccine and intramuscularly immunized two or three times. We found that BCG-PSN could significantly improve the immunogenicity of DNA vaccine when co-administered with DNA vaccine. Further, at the same vaccination schedule, BCG-PSN co-immunization with 10 μg DNA vaccine could elicit cellular and humoral immune responses which were comparable to that induced by 100 μg DNA vaccine alone. Moreover, our results demonstrate that BCG-PSN can activate TLR signaling pathways and induce Th1-type cytokines secretion. These findings suggest that BCG-PSN can serve as a novel and effective adjuvant for DNA vaccination.
Fuchs, Jonathan D; Bart, Pierre-Alexandre; Frahm, Nicole; Morgan, Cecilia; Gilbert, Peter B; Kochar, Nidhi; DeRosa, Stephen C; Tomaras, Georgia D; Wagner, Theresa M; Baden, Lindsey R; Koblin, Beryl A; Rouphael, Nadine G; Kalams, Spyros A; Keefer, Michael C; Goepfert, Paul A; Sobieszczyk, Magdalena E; Mayer, Kenneth H; Swann, Edith; Liao, Hua-Xin; Haynes, Barton F; Graham, Barney S; McElrath, M Juliana
Background Recombinant adenovirus serotype 5 (rAd5)-vectored HIV-1 vaccines have not prevented HIV-1 infection or disease and pre-existing Ad5 neutralizing antibodies may limit the clinical utility of Ad5 vectors globally. Using a rare Ad serotype vector, such as Ad35, may circumvent these issues, but there are few data on the safety and immunogenicity of rAd35 directly compared to rAd5 following human vaccination. Methods HVTN 077 randomized 192 healthy, HIV-uninfected participants into one of four HIV-1 vaccine/placebo groups: rAd35/rAd5, DNA/rAd5, and DNA/rAd35 in Ad5-seronegative persons; and DNA/rAd35 in Ad5-seropositive persons. All vaccines encoded the HIV-1 EnvA antigen. Antibody and T-cell responses were measured 4 weeks post boost immunization. Results All vaccines were generally well tolerated and similarly immunogenic. As compared to rAd5, rAd35 was equally potent in boosting HIV-1-specific humoral and cellular immunity and responses were not significantly attenuated in those with baseline Ad5 seropositivity. Like DNA, rAd35 efficiently primed rAd5 boosting. All vaccine regimens tested elicited cross-clade antibody responses, including Env V1/V2-specific IgG responses. Conclusions Vaccine antigen delivery by rAd35 is well-tolerated and immunogenic as a prime to rAd5 immunization and as a boost to prior DNA immunization with the homologous insert. Further development of rAd35-vectored prime-boost vaccine regimens is warranted. PMID:26587311
The World Health Organization estimates that 50% of the 30 million HIV infections worldwide occurred in young people between the ages of 15 and 24 years. In the United States, national statistics estimate that almost 40% of new HIV cases occur in youth ages 13-29 (Centers for Disease Control and Prevention, 2011). Therefore, a focus on preventing…
Takeuchi, Jiro; Goto, Masashi; Kawamura, Takashi; Hiraide, Atsushi
Japan experienced measles outbreaks in both 2006 and 2007 mainly among university students. Improvement of vaccine coverage against vaccine-preventable viral infections is the prime task for preventing outbreaks of viral infections. To elucidate the promoting factors for complete vaccination against measles, rubella, mumps, and varicella-zoster viruses, we conducted a case-control study among single university students in Japan. Information on vaccinations and clinico-demographical factors were collected using a self-administered questionnaire and a photocopy of the Maternal and Child Health Handbook. Logistic regression analysis was performed to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) for two-time vaccination against measles and rubella viruses as mandatory vaccinations and at least one-time vaccination against mumps and varicella-zoster viruses as optional vaccinations. A total of 1,370 (744 medical, 508 paramedical, and 118 pharmaceutical) students were invited to participate, 960 (70.1%) of whom were enrolled in the study. Students aged < 20 years had a greater propensity for measles and rubella vaccinations (OR 7.8 [95% CI, 5.1-11.8] and OR 6.1 [95% CI, 3.7-10.0], respectively) compared with those aged ≥ 20 years. Students with a history of living over-seas for 1 month or longer were more likely to complete vaccination for measles (OR 4.4 [95% CI, 1.4-13.5] compared with those without such history. This significantly high vaccination coverage was attributed to the measles-rubella catch-up campaign by the Japanese government and the immunization regulations by foreign countries. These findings suggest that social regulations would predispose people to complete vaccination.
Sheets, Rebecca L; Zhou, TieQun; Knezevic, Ivana
Clinical development of prophylactic HIV/AIDS vaccines presents many scientific challenges that result in challenges for regulators reviewing clinical trial applications (CTAs). The World Health Organization (WHO) has the responsibility to provide technical support to these regulators. The search for an HIV/AIDS vaccine will only succeed through well-designed, -conducted and -controlled human efficacy studies reviewed and approved by regulators in countries worldwide, particularly in countries where the epidemic has hit hardest, such as in sub-Saharan Africa and Asia. This review summarizes the current candidates in development and focuses on challenges regulators face when reviewing CTAs, such as the evolving landscape of "standard of prevention," trials in adolescents, adaptive trial designs, correlates of protection and their analysis, and access to successful vaccines. There are many unknowns in the field of HIV/AIDS vaccine development and often, there is not a clear right or wrong approach because of the scientific challenges described in this review. Consequently, regulators should not feel that decisions need be made in isolation, when there are many available international collaborative efforts and opportunities to seek expert advice. The WHO provides many such opportunities and support to regulators across the globe.
D'Souza, Clare; Mort, Gillian Sullivan; Zyngier, Suzanne; Robinson, Priscilla; Schlotterlein, Morgan
Much of the literature has been conducted on innovation; this research provides new insights for preventive innovations that increase our understanding of vaccination diffusion and the reasons underlying the complexity of preventive diffusion. The research uses adoption of Rogers' ( 1983 ) perceived characteristics and considers the rate by which a product diffuses in a market. Qualitative empirical evidence collected via focus groups is used to identify human papillomavirus vaccine issues against the salience of perceived characteristics. Several impediments are identified and the application of marketing strategies is suggested for preventive innovations to improve the diffusion process and for designing proactive adoption.
Casals-Sánchez, J L; Casals Vázquez, C; Vázquez Sánchez, M Á; Giménez Basallote, S
Patients with inflammatory arthritis and eligible for immunosuppressive therapy account for more than 1% of general population, and represents a significant workload on family doctors. They are prone to other comorbidities, with an increased cardiovascular risk and a higher incidence of infections than the general population, especially skin infections and pneumonitis. This comorbidity can be considered vulnerable to a prevention program-prevention of cardiovascular risk, cancer screening, vaccination schedule for adults. As for prevention through vaccination, importance should be given to pneumococcal infection - significant in adults aged 50 or over, especially amongst immunosuppressed patients. The 13-valent conjugate vaccine, which has been recently approved for adults, must be considered. An attempt has been made to write a simple, applicable document on preventive measures that should be implemented both at primary and secondary care level for those adults.
Hoyte, Tamika; Purcell, David W.; Van Handel, Michelle; Williams, Weston; Krueger, Amy; Dietz, Patricia; Stratford, Dale; Heitgerd, Janet; Dunbar, Erica; Wan, Choi; Linley, Laurie A.; Flores, Stephen A.
Objective The Enhanced Comprehensive HIV Prevention Planning project was the first initiative of the Centers for Disease Control and Prevention (CDC) to address the goals of the National HIV/AIDS Strategy (NHAS). Health departments in 12 U.S. cities with a high prevalence of AIDS conducted comprehensive program planning and implemented cost-effective, scalable HIV prevention interventions that targeted high-risk populations. We examined trends in health department HIV prevention programs in these cities during the project. Methods We analyzed the number of people who received partner services, condoms distributed, and people tested for HIV, as well as funding allocations for selected HIV prevention programs by year and by site from October 2010 through September 2013. We assessed trends in the proportional change in services and allocations during the project period using generalized estimating equations. We also conducted thematic coding of program activities that targeted people living with HIV infection (PLWH). Results We found significant increases in funding allocations for HIV testing and condom distribution. All HIV partner services indicators, condom distribution, and HIV testing of African American and Hispanic/Latino populations significantly increased. HIV tests associated with a new diagnosis increased significantly among those self-identifying as Hispanic/Latino but significantly decreased among African Americans. For programs targeting PLWH, health department activities included implementing new program models, improving local data use, and building local capacity to enhance linkage to HIV medical care, retention in care, and treatment adherence. Conclusions Overall, these findings indicate that health departments in areas with a high burden of AIDS successfully shifted their HIV prevention resources to scale up important HIV programs and make progress toward NHAS goals. PMID:26843685
Phadke, Varun K.; Bednarczyk, Robert A.; Salmon, Daniel A.; Omer, Saad B.
IMPORTANCE Parents hesitant to vaccinate their children may delay routine immunizations or seek exemptions from state vaccine mandates. Recent outbreaks of vaccine-preventable diseases in the United States have drawn attention to this phenomenon. Improved understanding of the association between vaccine refusal and the epidemiology of these diseases is needed. OBJECTIVE To review the published literature to evaluate the association between vaccine delay, refusal, or exemption and the epidemiology of measles and pertussis, 2 vaccine-preventable diseases with recent US outbreaks. EVIDENCE REVIEW Search of PubMed through November 30, 2015, for reports of US measles outbreaks that have occurred since measles was declared eliminated in the United States (after January 1, 2000), endemic and epidemic pertussis since the lowest point in US pertussis incidence (after January 1, 1977), and for studies that assessed disease risk in the context of vaccine delay or exemption. FINDINGS We identified 18 published measles studies (9 annual summaries and 9 outbreak reports), which described 1416 measles cases (individual age range, 2 weeks-84 years; 178 cases younger than 12 months) and more than half (56.8%) had no history of measles vaccination. Of the 970 measles cases with detailed vaccination data, 574 cases were unvaccinated despite being vaccine eligible and 405 (70.6%) of these had nonmedical exemptions (eg, exemptions for religious or philosophical reasons, as opposed to medical contraindications; 41.8%of total). Among 32 reports of pertussis outbreaks, which included 10 609 individuals for whom vaccination status was reported (age range, 10 days-87 years), the 5 largest statewide epidemics had substantial proportions (range, 24%–45%) of unvaccinated or undervaccinated individuals. However, several pertussis outbreaks also occurred in highly vaccinated populations, indicating waning immunity. Nine reports (describing 12 outbreaks) provided detailed vaccination data on
Staehelin, Cornelia; Hirzel, Cédric; Hauser, Christoph; Furrer, Hansjakob
Patients with an acquired immune deficiency, for example due to HIV-infection, after a solid organ or haematological stem cell transplantation or due to functional or anatomical asplenia, have a greater risk to experience severe complications or a chronic course of infection compared to healthy individuals. Vaccinations would pose an ideal primary preventive method. However, their efficacy is reduced if applied during the immunosuppressed period. Therefore, whenever possible, vaccinations should be administered before the period of immunosuppression starts – or caught up later during the period of minimal possible immunosuppression. Nevertheless, the benefit conveyed through vaccines is undisputed, particularly if indications regarding dosing of vaccines (amount and frequency of doses) are optimized according to the given state of immunosuppression. Live attenuated vaccines are contraindicated during severe immunosuppression. Serologies should still be analysed and documented however, since these vulnerable patients require passive immunization through specific or standard intravenous immunoglobulins in case of relevant exposure to the respective antigens. For all patients therefore, careful documentation and communication of previous vaccinations and serologies (protective or not) among the various medical specialties is required to optimize patient management. For all immunosuppressed patients the efficacy of polysaccharide vaccines (such as the pneumococcal and meningococcal vaccines PSV-23 and MPV-ACWY) is strongly reduced compared to the conjugated ones (PCV13 and MCV-ACWY). Therefore, contrary to most other national guidelines, the Swiss guidelines recommend to use only the conjugated versions in primary vaccination series as well as in boosters – this applies strongly for immunosuppressed patients, but is recommended also for the general population in Switzerland. Another common management recommendation specific for transplant patients is the indication
Peñaranda, Maria; Payeras, Antoni; Cambra, Ana; Mila, Joan; Riera, Melcior
This is a randomized trial to compare the immunoglobulin G response and the antibody avidity after two pneumococcal vaccinations, conjugated pneumococcal vaccine (CPV) and polysaccharide pneumococcal vaccine (PPV) 4 weeks after vs. PPV alone in 202 HIV-infected adults. There were no differences in the two strategies, either in the percentage of immunoglobulin G two-fold increase for the CPV included serotypes or immunoglobulin G two-fold increase, reaching the level of 1 microg/ml except for serotype 23F (26% responded after conjugated pneumococcal vaccine + PPV vs. 14% after PPV). No avidity increases were seen in any strategy.
Gach, Johannes S.; Gorlani, Andrea; Dotsey, Emmanuel Y.; Becerra, Juan C.; Anderson, Chase T. M.; Berzins, Baiba; Felgner, Philip L.; Forthal, Donald N.; Deeks, Steven G.; Wilkin, Timothy J.; Casazza, Joseph P.; Koup, Richard A.; Katlama, Christine; Autran, Brigitte; Murphy, Robert L.; Achenbach, Chad J.
Little is known about the humoral immune response against DNA prime-recombinant adenovirus 5 (rAd5) boost HIV vaccine among HIV-infected patients on long-term suppressive antiretroviral therapy (ART). Previous studies emphasized cellular immune responses; however, current research suggests both cellular and humoral responses are likely required for a successful therapeutic vaccine. Thus, we aimed to understand antibody response and function induced by vaccination of ART-treated HIV-1-infected patients with immune recovery. All subjects participated in EraMune 02, an open-label randomized clinical trial of ART intensification followed by a six plasmid DNA prime (envA, envB, envC, gagB, polB, nefB) and rAd5 boost HIV vaccine with matching inserts. Antibody binding levels were determined with a recently developed microarray approach. We also analyzed neutralization efficiency and antibody-dependent cellular cytotoxicity (ADCC). We found that the DNA prime-rAd5 boost vaccine induced a significant cross-clade HIV-specific antibody response, which correlated with antibody neutralization efficiency. However, despite the increase in antibody binding levels, the vaccine did not significantly stimulate neutralization or ADCC responses. This finding was also reflected by a lack of change in total CD4+ cell associated HIV DNA in those who received the vaccine. Our results have important implications for further therapeutic vaccine design and administration, especially in HIV-1 infected patients, as boosting of preexisting antibody responses are unlikely to lead to clearance of latent proviruses in the HIV reservoir. PMID:27500639
The bulk of current HIV vaccine research is conducted within the infectious disease paradigm that has been very successful in developing vaccines against many other viral diseases. Different HIV vaccine concepts, based on the induction of neutralizing antibodies and/or cell mediated immunity, have been developed and clinically tested over the last 30 years, resulting in a few small successes and many disappointments. As new scientific knowledge is obtained, HIV vaccine concepts are constantly modified with the hope that the newly introduced tweaks (or paradigm drifts) will provide the solution to one of the most difficult challenges that modern biomedical research is confronting. Efficacy trials have been critical in guiding HIV vaccine development. However, from the five phase III efficacy trials conducted to date, only one (RV144) resulted in modest efficacy. The results from RV144 were surprising in many ways, including the identified putative correlates of protection (or risk), which did not include neutralizing antibodies or cytotoxic T-cells. The solution to the HIV vaccine challenge may very well come from approaches based on the current paradigm. However, at the same time, out-of-the-paradigm ideas should be systematically explored to complement the current efforts. New mechanisms are needed to identify and support the innovative research that will hopefully accelerate the development of an urgently needed HIV vaccine. PMID:25852692
Scott, Yanille M; Park, Seo Young; Dezzutti, Charlene S
Broadly neutralizing monoclonal antibodies (nAbs) specific for HIV are being investigated for use in HIV prevention. Due to their ability to inhibit HIV attachment to and entry into target cells, nAbs may be suitable for use as topical HIV microbicides. As such, they would present an alternative intervention for individuals who may not benefit from using antiretroviral-based products for HIV prevention. We theorize that nAbs can inhibit viral transmission through mucosal tissue, thus reducing the incidence of HIV infection. The efficacy of the PG9, PG16, VRC01, and 4E10 antibodies was evaluated in an ex vivo human model of mucosal HIV transmission. nAbs reduced HIV transmission, causing 1.5- to 2-log10 reductions in HIV replication in ectocervical tissues and ≈3-log10 reductions in HIV replication in colonic tissues over 21 days. These antibodies demonstrated greater potency in colonic tissues, with a 50-fold higher dose being required to reduce transmission in ectocervical tissues. Importantly, nAbs retained their potency and reduced viral transmission in the presence of whole semen. No changes in tissue viability or immune activation were observed in colonic or ectocervical tissue after nAb exposure. Our data suggest that topically applied nAbs are safe and effective against HIV infection of mucosal tissue and support further development of nAbs as a topical microbicide that could be used for anal as well as vaginal protection.
Scott, Yanille M.; Park, Seo Young
Broadly neutralizing monoclonal antibodies (nAbs) specific for HIV are being investigated for use in HIV prevention. Due to their ability to inhibit HIV attachment to and entry into target cells, nAbs may be suitable for use as topical HIV microbicides. As such, they would present an alternative intervention for individuals who may not benefit from using antiretroviral-based products for HIV prevention. We theorize that nAbs can inhibit viral transmission through mucosal tissue, thus reducing the incidence of HIV infection. The efficacy of the PG9, PG16, VRC01, and 4E10 antibodies was evaluated in an ex vivo human model of mucosal HIV transmission. nAbs reduced HIV transmission, causing 1.5- to 2-log10 reductions in HIV replication in ectocervical tissues and ≈3-log10 reductions in HIV replication in colonic tissues over 21 days. These antibodies demonstrated greater potency in colonic tissues, with a 50-fold higher dose being required to reduce transmission in ectocervical tissues. Importantly, nAbs retained their potency and reduced viral transmission in the presence of whole semen. No changes in tissue viability or immune activation were observed in colonic or ectocervical tissue after nAb exposure. Our data suggest that topically applied nAbs are safe and effective against HIV infection of mucosal tissue and support further development of nAbs as a topical microbicide that could be used for anal as well as vaginal protection. PMID:26596954
Buisson, Y; Meyran, M
In spite of low endemic levels in France, hepatitis A and hepatitis B remains major concerns for public health. Seroprevalence of antibodies against hepatitis A (anti-HAV), declining below 15% in the 20 years-aged subjects, highlights an increasing susceptibility to hepatitis A. Later in the life, HAV infections become more serious and expansive. Control measures against hepatitis B have nearly stopped HBV spread linked to blood transfusions and mothers to infants transmission. Now, common risk factors are first sexual exposure, then injecting drug use, especially among young people. Vaccination is recognized as the most effective process for prevention. Recombinant hepatitis B vaccines have taken the place of plasma-derived vaccines. Although non responder individuals and escape mutants of HBV may hamper vaccinal coverage, hepatitis vaccines are highly immunogenic in immunocompetent people, allowing simplified schedules and reduced HBsAg dosages for children. Inactivated HAV vaccines now licensed prove to be highly immunogenic after only one injection. Hepatitis B vaccination targeted on high risk groups remains imperative but inadequate for reducing hepatitis B occurrence. A universal hepatitis B vaccination program in childhood and early adolescence would nearly stop the spread of HBV in the populations before ten years. Likewise, hepatitis A vaccination of travelers to endemic areas, all individuals exposed to contaminations from fecal sources, and food handlers, could reduce the spread of HAV in the community but would not completely prevent outbreaks of hepatitis A. Advantages of universal immunization of babies are not proved yet. Implementation of preventive strategies first needs a comprehensive surveillance of viral hepatitis in France.
Buisson, Y; Meyran, M
In spite of low endemic levels in France, hepatitis A and hepatitis B remain major concerns for public health. Seroprevalence of antibodies against hepatitis A (anti-HAV), declining below 15% in the 20 years-aged subjects, highlights an increasing susceptibility to hepatitis A. Later in the life, HAV infections become more serious and expansive. Control measures against hepatitis B have nearly stopped HBV spread linked to blood transfusions and mothers to infants transmission. Now, common risk factors are first sexual exposure, then injecting drug use, especially among young people. Vaccination is recognized as the most effective process for prevention. Recombinant hepatitis B vaccines have taken the place of plasma-derived vaccines. Although non responder individuals and escape mutants of HBV may hamper vaccinal coverage, hepatitis vaccines are highly immunogenic in immunocompetent people, allowing simplified schedules and reduced HBsAg dosages for children. Inactivated HAV vaccines now licensed prove to be highly immunogenic after only one injection. Hepatitis B vaccination targeted on high risk groups remains imperative but inadequate for reducing hepatitis B occurrence. A universal hepatitis B vaccination program in childhood and early adolescence would nearly stop the spread of HBV in the populations before ten years. Likewise, hepatitis A vaccination of travelers to endemic areas, all individuals exposed to contaminations from fecal sources, and food handlers, could reduce the spread of HAV in the community but would not completely prevent outbreaks of hepatitis A. Advantages of universal immunization of babies are not proved yet. Implementation of preventive strategies first needs a comprehensive surveillance of viral hepatitis in France.
Tomaras, Georgia D; Haynes, Barton F
Interrogating immune correlates of infection risk for efficacious and non-efficacious HIV-1 vaccine clinical trials have provided hypotheses regarding the mechanisms of induction of protective immunity to HIV-1. To date, there have been six HIV-1 vaccine efficacy trials (VAX003, Vaxgen, Inc., San Francisco, CA, USA), VAX004 (Vaxgen, Inc.), HIV-1 Vaccine Trials Network (HVTN) 502 (Step), HVTN 503 (Phambili), RV144 (sponsored by the U.S. Military HIV Research Program, MHRP) and HVTN 505). Cellular, humoral, host genetic and virus sieve analyses of these human clinical trials each can provide information that may point to potentially protective mechanisms for vaccine-induced immunity. Critical to staying on the path toward development of an efficacious vaccine is utilizing information from previous human and non-human primate studies in concert with new discoveries of basic HIV-1 host-virus interactions. One way that past discoveries from correlate analyses can lead to novel inventions or new pathways toward vaccine efficacy is to examine the intersections where different components of the correlate analyses overlap (e.g., virus sieve analysis combined with humoral correlates) that can point to mechanistic hypotheses. Additionally, differences in durability among vaccine-induced T- and B-cell responses indicate that time post-vaccination is an important variable. Thus, understanding the nature of protective responses, the degree to which such responses have, or have not, as yet, been induced by previous vaccine trials and the design of strategies to induce durable T- and B-cell responses are critical to the development of a protective HIV-1 vaccine.
Enah, Comfort; Moneyham, Linda; Vance, David E; Childs, Gwendolyn
The search for intervention strategies appropriate for young adolescents has recently led to the use of digital games. Digital gaming interventions are promising because they may be developmentally appropriate for adolescent populations. The gaming approach also capitalizes on an inherent interest to adolescents and circumvents traditional barriers to access to prevention interventions faced in some geographical areas. Notwithstanding, research on gaming in HIV prevention is quite limited. In this review article, we examine the need for contextually relevant HIV prevention interventions among young adolescents. From this, we provide a theoretical framework for exploring contextually relevant HIV risk factors and a foundation for gathering and using input from the target population to adapt an existing game or to create a developmentally appropriate and contextually relevant HIV prevention game.
Grijsen, ML; Graham, SM; Mwangome, M; Githua, P; Mutimba, S; Wamuyu, L; Okuku, H; Price, MA; McClelland, RS; Smith, AD; Sanders, EJ
Objectives To demonstrate the value of routine, basic sexually transmitted infection (STI) screening at enrolment into an HIV-1 vaccine feasibility cohort study and to highlight the importance of soliciting a history of receptive anal intercourse (RAI) in adults identified as ‘high risk’. Methods Routine STI screening was offered to adults at high risk for HIV-1 upon enrolment into a cohort study in preparation for HIV-1 vaccine trials. Risk behaviors and STI prevalence were summarized, and the value of microscopy assessed. Associations between prevalent HIV-1 infection and RAI or prevalent STIs were evaluated with multiple logistic regression. Results Participants had a high burden of untreated STIs. Symptom-directed management would have missed 67% of urethritis cases in men and 59% of cervicitis cases in women. RAI was reported by 36% of male and 18% of female participants. RAI was strongly associated with HIV-1 in men (adjusted odds ratio [aOR] = 3.8, 95% CI 2.0 – 6.9), and independently associated with syphilis in women (aOR 12.9, 95% CI 3.4 – 48.7). Conclusions High-risk adults recruited for HIV-1 prevention trials carry a high STI burden. Symptom-directed treatment may miss many cases, and simple laboratory-based screening can be done with little cost. Risk assessment should include questions about anal intercourse and whether condoms were used. STI screening, including specific assessment for anorectal disease, should be offered in African research settings recruiting participants at high risk for HIV-1 acquisition. PMID:18375645
Reis, Janet S.; Weber, Kathleen M.
Objectives. We examined HIV-infected parents’ conversations about HIV prevention with their uninfected children, including what facilitated or hindered communication. Methods. Parents with HIV/AIDS (n = 90) who had children aged 10 to 18 years were recruited for a mixed method study from 2009 to 2010. Interviews assessed facilitators and barriers to discussing HIV prevention. A questionnaire identified the frequency and content of conversations, parental confidence level, and perceived importance of discussing preventive topics. Results. Eighty-one percent of parents reported “sometimes” or “often” communicating about HIV prevention. A subset of parents found these conversations difficult; 44% indicated their desire for support. Facilitators to communication included utilizing support, focusing on the benefits of talking, and having a previous relationship with one’s child. Barriers to discussions included fear of negative consequences, living in denial, and lacking a parental role model who discussed safer sex. Parents varied as to how they believed their HIV status affected communication. Those who did not disclose their HIV status to their children reported less frequent communication; self-efficacy partially mediated this relationship. Conclusions. Findings highlighted the need for communication skills training that support HIV-infected parents in their efforts to discuss HIV-related information with adolescents. PMID:23763390
Lippman, Sheri A.; Treves-Kagan, Sarah; Gilvydis, Jennifer M.; Naidoo, Evasen; Khumalo-Sakutukwa, Gertrude; Darbes, Lynae; Raphela, Elsie; Ntswane, Lebogang; Barnhart, Scott
Objective Building a successful combination prevention program requires understanding the community’s local epidemiological profile, the social community norms that shape vulnerability to HIV and access to care, and the available community resources. We carried out a situational analysis in order to shape a comprehensive HIV prevention program that address local barriers to care at multiple contextual levels in the North West Province of South Africa. Method The situational analysis was conducted in two sub-districts in 2012 and guided by an adaptation of WHO’s Strategic Approach, a predominantly qualitative method, including observation of service delivery points and in-depth interviews and focus groups with local leaders, providers, and community members, in order to recommend context-specific HIV prevention strategies. Analysis began during fieldwork with nightly discussions of findings and continued with coding original textual data from the fieldwork notebooks and a select number of recorded interviews. Results We conducted over 200 individual and group interviews and gleaned four principal social barriers to HIV prevention and care, including: HIV fatalism, traditional gender norms, HIV-related stigma, and challenges with communication around HIV, all of which fuel the HIV epidemic. At the different levels of response needed to stem the epidemic, we found evidence of national policies and programs that are mitigating the social risk factors but little community-based responses that address social risk factors to HIV. Conclusions Understanding social and structural barriers to care helped shape our comprehensive HIV prevention program, which address the four ‘themes’ identified into each component of the program. Activities are underway to engage communities, offer community-based testing in high transmission areas, community stigma reduction, and a positive health, dignity and prevention program for stigma reduction and improve communication skills
Gnann, John W
Widespread use of varicella vaccine in the United States has drastically changed the epidemiology of the disease. Although chickenpox is no longer a ubiquitous childhood infection, varicella-zoster virus continues to circulate in the community and nonimmune pregnant women remain at risk. Varicella can cause severe infection in pregnant women, often complicated by viral pneumonia. Maternal varicella occurring in the first half of pregnancy can cause the rare but devastating congenital varicella syndrome, whereas infection in the late stages of pregnancy may cause neonatal varicella. The best approach to avoiding the morbidity and mortality associated with chickenpox in pregnancy is to screen and vaccinate susceptible reproductive-age women.
Ryan, Una S; Rittershaus, Charles W
Atherosclerosis, especially coronary heart disease (CHD), remains a most significant global public health problem. Highly effective LDL-lowering therapies have gained widespread adoption in the United States and throughout the developed world, but therapeutic options for raising low HDL, a key independent risk factor for CHD, remain limited. We are developing a vaccine approach to raising HDL, by inducing an immune response to endogenous cholesteryl ester transfer protein (CETP), and have demonstrated proof of principle in preclinical and clinical models. This vaccine approach may offer the opportunity to address low HDL with a cost-effective semi-annual injection.
Louise McCormick, A.; Mocarski, Edward S.
A universal cytomegalovirus (CMV) vaccination promises to reduce the burden of the developmental damage that afflicts up to 0.5% of live births worldwide. An effective vaccination that prevents transplacental transmission would reduce CMV congenital disease and CMV-associated still births and leave populations less susceptible to opportunistic CMV disease. Thus, a vaccination against this virus has long been recognized for the potential of enormous health-care savings because congenital damage is life-long and existing anti-viral options are limited. Vaccine researchers, industry leaders, and regulatory representatives have discussed the challenges posed by clinical efficacy trials that would lead to a universal CMV vaccine, reviewing the links between infection and disease, and identifying settings where disrupting viral transmission might provide a surrogate endpoint for disease prevention. Reducing the complexity of such trials would facilitate vaccine development. Children and adolescents are the targets for universal vaccination, with the expectation of protecting the offspring of immunized women. Given that a majority of females worldwide experience CMV infection during childhood, a universal vaccine must boost natural immunity and reduce transmission due to reactivation and re-infection as well as primary infection during pregnancy. Although current vaccine strategies recognize the value of humoral and cellular immunity, the precise mechanisms that act at the placental interface remain elusive. Immunity resulting from natural infection appears to limit rather than prevent reactivation of latent viruses and susceptibility to re-infection, leaving a challenge for universal vaccination to improve upon natural immunity levels. Despite these hurdles, early phase clinical trials have achieved primary end points in CMV seronegative subjects. Efficacy studies must be expanded to mixed populations of CMV-naive and naturally infected subjects to understand the overall
Castilla, Jesús; Guevara, Marcela; Martínez-Baz, Iván; Ezpeleta, Carmen; Delfrade, Josu; Irisarri, Fátima; Moreno-Iribas, Conchi
Abstract Mortality is a major end-point in the evaluation of influenza vaccine effectiveness. However, this effect is not well known, since most previous studies failed to show good control of biases. We aimed to estimate the effectiveness of influenza vaccination in preventing all-cause mortality in community-dwelling seniors. Since 2009, a population-based cohort study using healthcare databases has been conducted in Navarra, Spain. In 2 late influenza seasons, 2011/2012 and 2012/2013, all-cause mortality in the period January to May was compared between seniors (65 years or over) who received the trivalent influenza vaccine and those who were unvaccinated, adjusting for demographics, major chronic conditions, dependence, previous hospitalization, and pneumococcal vaccination. The cohort included 103,156 seniors in the 2011/2012 season and 105,140 in the 2012/2013 season (58% vaccinated). Seniors vaccinated in the previous season who discontinued vaccination (6% of the total) had excess mortality and were excluded to prevent frailty bias. The final analysis included 80,730 person-years and 2778 deaths. Vaccinated seniors had 16% less all-cause mortality than those unvaccinated (adjusted rate ratio [RR] = 0.84; 95% confidence interval 0.76–0.93). This association disappeared in the post-influenza period (adjusted RR = 0.96; 95% confidence interval 0.85–1.09). A similar comparison did not find an association in January to May of the 2009/2010 pandemic season (adjusted RR = 0.98; 95% confidence interval 0.84–1.14), when no effect of the seasonal vaccine was expected. On average, 1 death was prevented for every 328 seniors vaccinated: 1 for every 649 in the 65 to 74 year age group and 1 for every 251 among those aged 75 and over. These results suggest a moderate preventive effect and a high potential impact of the seasonal influenza vaccine against all-cause mortality. This reinforces the recommendation of annual influenza vaccination in seniors
Gottlieb, Sami L; Low, Nicola; Newman, Lori M; Bolan, Gail; Kamb, Mary; Broutet, Nathalie
An estimated 499 million curable sexually transmitted infections (STIs; gonorrhea, chlamydia, syphilis, and trichomoniasis) occurred globally in 2008. In addition, well over 500 million people are estimated to have a viral STI such as herpes simplex virus type 2 (HSV-2) or human papillomavirus (HPV) at any point in time. STIs result in a large global burden of sexual, reproductive, and maternal-child health consequences, including genital symptoms, pregnancy complications, cancer, infertility, and enhanced HIV transmission, as well as important psychosocial consequences and financial costs. STI control strategies based primarily on behavioral primary prevention and STI case management have had clear successes, but gains have not been universal. Current STI control is hampered or threatened by several behavioral, biological, and implementation challenges, including a large proportion of asymptomatic infections, lack of feasible diagnostic tests globally, antimicrobial resistance, repeat infections, and barriers to intervention access, availability, and scale-up. Vaccines against HPV and hepatitis B virus offer a new paradigm for STI control. Challenges to existing STI prevention efforts provide important reasons for working toward additional STI vaccines. We summarize the global epidemiology of STIs and STI-associated complications, examine challenges to existing STI prevention efforts, and discuss the need for new STI vaccines for future prevention efforts.
Rosewell, Alexander; Spokes, Paula; Gilmour, Robin
We aim to describe the epidemiology of selected vaccine-preventable diseases in New South Wales (NSW) for 2012. Data from the NSW Notifiable Conditions Information Management System were analysed by: local health district of residence, age, Aboriginality, vaccination status and organism, where available. Risk factor and vaccination status data were collected by public health units for cases following notification under the NSW Public Health Act 2010. The largest outbreak of measles since 1998 was reported in 2012. Pacific Islander and Aboriginal people were at higher risk as were infants less than 12 months of age. Notifications of invasive pneumococcal disease (IPD) in children less than five years declined; however, the overall number of notifications for IPD increased. Mumps case notifications were also elevated. There were no Haemophilus influenzae type b case notifications in children less than five years of age for the first time since the vaccine was introduced. Invasive meningococcal disease case notifications were at their lowest rates since case notification began in 1991. Case notification rates for other selected vaccine-preventable diseases remained stable. Vaccine-preventable disease control is continually strengthening in NSW with notable successes in invasive bacterial infections. However, strengthening measles immunization in Pacific Islander and Aboriginal communities remains essential to maintain measles elimination.
Evangeli, Michael; Kafaar, Zuhayr; Kagee, Ashraf; Swartz, Leslie; Bullemor-Day, Philippa
It is vital that enough participants are willing to participate in clinical trials to test HIV vaccines adequately. It is, therefore, necessary to explore what affects peoples' willingness to participate (WTP) in such trials. Studies have only examined individual factors associated with WTP and not the effect of messages about trial participation on potential participants (e.g., whether losses or gains are emphasized, or whether the outcome is certain or uncertain). This study explores whether the effects of message framing on WTP in a hypothetical HIV vaccine trial are consistent with Prospect Theory. This theory suggests that people are fundamentally risk averse and that (1) under conditions of low risk and high certainty, gain-framed messages will be influential (2) under conditions of high risk and low certainty, loss-framed messages will be influential. This cross-sectional study recruited 283 HIV-negative students from a South African university who were given a questionnaire that contained matched certain gain-framed, certain loss-framed, uncertain gain-framed, and uncertain loss-framed statements based on common barriers and facilitators of WTP. Participants were asked to rate how likely each statement was to result in their participation in a hypothetical preventative HIV vaccine trial. Consistent with Prospect Theory predictions, for certain outcomes, gain-framed messages were more likely to result in WTP than loss-framed messages. Inconsistent with predictions, loss-framed message were not more likely to be related to WTP for uncertain outcomes than gain-framed messages. Older students were less likely to express their WTP across the different message frames. Recruitment for HIV vaccine trials should pay attention to how messages about the trial are presented to potential participants.
Carne, C A; Weller, I V; Waite, J; Briggs, M; Pearce, F; Adler, M W; Tedder, R S
Thirty five homosexual men (17 positive for antibody to the human immunodeficiency virus (HIV) and 18 consistently negative) were vaccinated against hepatitis B virus infection. Eight of the 17 seropositive patients failed to develop detectable hepatitis B surface antibody within three months of the third injection compared with only one of the 18 seronegative patients (p less than 0.01). HIV infection is prevalent in the developed world in groups at risk for hepatitis B infection and in certain Third World countries where widespread vaccination programmes exist. This study shows the impact that coincident HIV infection may have on an otherwise efficacious vaccine. The efficacy of this and other vaccines in patients infected with HIV needs to be studied urgently.
Baggaley, Rachel; Dalal, Shona; Johnson, Cheryl; Macdonald, Virginia; Mameletzis, Ioannis; Rodolph, Michelle; Figueroa, Carmen; Samuelson, Julia; Verster, Annette; Doherty, Meg; Hirnschall, Gottfried
Introduction The remarkable expansion in availability of antiretroviral therapy (ART) over the past two decades has transformed HIV infection into a manageable chronic condition. People with HIV infection now live long and healthy lives on treatment that is simpler, safer and cheaper. According to UNAIDS estimates, the global coverage of ART reached 46% in 2015, resulting in a 26% decrease in annual HIV-related deaths since 2010. Such success has positioned treatment access at the centre of the global HIV response as a way to prevent mortality, morbidity and HIV transmission through a “Treat All” approach. Continuing expansion of treatment is needed to further reduce HIV-related mortality. This progress with treatment, however, masks a stagnation in the estimated annual number of new HIV infections. Continuing levels of HIV incidence despite treatment scale-up stem from several factors, which should be addressed in order to prevent new infections and decrease the numbers of people requiring treatment in the future. Discussion ART can only reach those already diagnosed, and although it is unclear what proportion of new infections occur during acute and early infection prior to treatment initiation, phylogenetic studies suggest that it might be substantial. Thus, better testing approaches to reach the 40% of people with undiagnosed HIV infection as early as possible are critical. New approaches to reach men, young people and key populations, where HIV risk is highest and HIV prevention, testing and treatment coverage is lowest, are also needed. Overall coverage of effective prevention interventions remains low, enabling HIV transmission to occur, or time is required to show population-level effects. For example, the full impact of the medical male circumcision intervention will be seen once a larger proportion of men in age cohorts with high incidence are circumcised. Finally, strategically focused pre-exposure prophylaxis interventions have the potential to
Leitner, Thomas; Campbell, Mary S; Mullins, James I; Hughes, James P; Wong, Kim G; Raugi, Dana N; Scrensen, Stefanie
HIV-1 sequencing has been used extensively in epidemiologic and forensic studies to investigate patterns of HIV-1 transmission. However, the criteria for establishing genetic linkage between HIV-1 strains in HIV-1 prevention trials have not been formalized. The Partners in Prevention HSV/HIV Transmission Study (ClinicaITrials.gov NCT00194519) enrolled 3408 HIV-1 serodiscordant heterosexual African couples to determine the efficacy of genital herpes suppression with acyclovir in reducing HIV-1 transmission. The trial analysis required laboratory confirmation of HIV-1 linkage between enrolled partners in couples in which seroconversion occurred. Here we describe the process and results from HIV-1 sequencing studies used to perform transmission linkage determination in this clinical trial. Consensus Sanger sequencing of env (C2-V3-C3) and gag (p17-p24) genes was performed on plasma HIV-1 RNA from both partners within 3 months of seroconversion; env single molecule or pyrosequencing was also performed in some cases. For linkage, we required monophyletic clustering between HIV-1 sequences in the transmitting and seroconverting partners, and developed a Bayesian algorithm using genetic distances to evaluate the posterior probability of linkage of participants sequences. Adjudicators classified transmissions as linked, unlinked, or indeterminate. Among 151 seroconversion events, we found 108 (71.5%) linked, 40 (26.5%) unlinked, and 3 (2.0%) to have indeterminate transmissions. Nine (8.3%) were linked by consensus gag sequencing only and 8 (7.4%) required deep sequencing of env. In this first use of HIV-1 sequencing to establish endpoints in a large clinical trial, more than one-fourth of transmissions were unlinked to the enrolled partner, illustrating the relevance of these methods in the design of future HIV-1 prevention trials in serodiscordant couples. A hierarchy of sequencing techniques, analysis methods, and expert adjudication contributed to the linkage
Jacobsen, Margo M.; Walensky, Rochelle P.
With HIV funding plateauing and the number of people living with HIV increasing due to the roll-out of life-saving antiretroviral therapy, policy makers are faced with increasingly tighter budgets to manage the ongoing HIV epidemic. Cost-effectiveness and modeling analyses can help determine which HIV interventions may be of best value. Incidence remains remarkably high in certain populations and countries, making prevention key to controlling the spread of HIV. This paper briefly reviews concepts in modeling and cost-effectiveness methodology, then examines results of recently published cost-effectiveness analyses on the following HIV prevention strategies: condoms and circumcision, behavioral or community-based interventions, prevention of mother to child transmission, HIV testing, pre-exposure prophylaxis, and treatment as prevention. We find that the majority of published studies demonstrate cost-effectiveness; however, not all interventions are affordable. We urge continued research on combination strategies and methodologies that take into account willingness to pay and budgetary impact. PMID:26830283
Jacobsen, Margo M; Walensky, Rochelle P
With HIV funding plateauing and the number of people living with HIV increasing due to the rollout of life-saving antiretroviral therapy, policy makers are faced with increasingly tighter budgets to manage the ongoing HIV epidemic. Cost-effectiveness and modeling analyses can help determine which HIV interventions may be of best value. Incidence remains remarkably high in certain populations and countries, making prevention key to controlling the spread of HIV. This paper briefly reviews concepts in modeling and cost-effectiveness methodology and then examines results of recently published cost-effectiveness analyses on the following HIV prevention strategies: condoms and circumcision, behavioral- or community-based interventions, prevention of mother-to-child transmission, HIV testing, pre-exposure prophylaxis, and treatment as prevention. We find that the majority of published studies demonstrate cost-effectiveness; however, not all interventions are affordable. We urge continued research on combination strategies and methodologies that take into account willingness to pay and budgetary impact.
Corey, Lawrence; Gilbert, Peter B.; Tomaras, Georgia; Haynes, Barton F.; Pantaleo, Giuseppe; Fauci, Anthony S.
Since 2009, the HIV vaccine field has worked to define correlates of risk associated with HIV-1 acquisition based upon the partial efficacy found in the RV144 trial. Both immunological and genetic pressure on the virus has been demonstrated by Fc antiviral antibodies largely directed at conserved regions of the V1V2 loop including antibody dependent cellular cytotoxicity (ADCC) to HIV envelope in the absence of inhibiting serum IgA antibodies. CD4+ T-cell responses to HIV envelope also correlate with reduced acquisition. Recently, NHP studies using vaccine regimens that differ from that used in RV144 also indicate that non-neutralizing antibodies are associated with protection from experimental lentivirus challenge. These immunological correlates have provided the basis for the design of a next generation of vaccine regimens to improve upon the qualitative and quantitative degree of magnitude of these immune responses on HIV acquisition. PMID:26491081
Any therapeutic vaccination approach against HIV-1 must induce CTL and Th1 cells. But, therapeutic vaccination is more than that. For extensive application of a therapeutic vaccine several questions need to be solved in advance to achieve a global impact. In this commentary some of them are addressed. We analyze the epidemiology, sociology, economy and immunopathology related to the HIV/AIDS disease. Also, important technical issues and real possibilities to overcome at least some of the major limitation of the antiretroviral treatments in the pursuit of an effective vaccine are considered. From the integration of previous analyses some conclusions are drawn. Because it is just a commentary some arguments are not unveiled into their full extension. At the end, we discuss some issues in relation to the development of the vaccine candidate TERAVAC-HIV-1 as a case study.
Holtgrave, D R; Harrison, J; Gerber, R A; Aultman, T V; Scarlett, M
To be effective, HIV prevention programs should be planned in partnership with affected communities and should be built on a solid scientific foundation. In 1994, the Centers for Disease Control and Prevention (CDC) and its prevention partners implemented HIV prevention community planning to achieve primarily these two objectives. In order to manage the community planning process effectively, extensive evaluation activities were employed at both the grantee and national level. This paper describes the first year evaluation goals and methods in detail. Throughout, reasons for collecting specific types of information and for using particular methodologies are highlighted. PMID:8862165
Santana, Vinicius C; Diniz, Mariana O; Cariri, Francisco A M O; Ventura, Armando M; Cunha-Neto, Edécio; Almeida, Rafael R; Campos, Marco A; Lima, Graciela K; Ferreira, Luís C S
Millions of people worldwide are currently infected with human papillomavirus (HPV), herpes simplex virus (HSV) or human immunodeficiency virus (HIV). For this enormous contingent of people, the search for preventive and therapeutic immunological approaches represents a hope for the eradication of latent infection and/or virus-associated cancer. To date, attempts to develop vaccines against these viruses have been mainly based on a monovalent concept, in which one or more antigens of a virus are incorporated into a vaccine formulation. In the present report, we designed and tested an immunization strategy based on DNA vaccines that simultaneously encode antigens for HIV, HSV and HPV. With this purpose in mind, we tested two bicistronic DNA vaccines (pIRES I and pIRES II) that encode the HPV-16 oncoprotein E7 and the HIV protein p24 both genetically fused to the HSV-1 gD envelope protein. Mice i.m. immunized with the DNA vaccines mounted antigen-specific CD8⁺ T cell responses, including in vivo cytotoxic responses, against the three antigens. Under experimental conditions, the vaccines conferred protective immunity against challenges with a vaccinia virus expressing the HIV-derived protein Gag, an HSV-1 virus strain and implantation of tumor cells expressing the HPV-16 oncoproteins. Altogether, our results show that the concept of a trivalent HIV, HSV, and HPV vaccine capable to induce CD8⁺ T cell-dependent responses is feasible and may aid in the development of preventive and/or therapeutic approaches for the control of diseases associated with these viruses.
Essack, Zaynab; Koen, Jennifer; Slack, Catherine; Lindegger, Graham; Newman, Peter A
Community engagement is crucial to ongoing development and testing of sorely needed new biomedical HIV prevention technologies. Yet, negative trial results raise significant challenges for community engagement in HIV prevention trials, including the early termination of the Cellulose Sulfate microbicide trial and two Phase IIb HIV vaccine trials (STEP and Phambili). The present study aimed to explore the perspectives and experiences of civil society organization (CSO) representatives regarding negative HIV prevention trial results and perceived implications for future trials. We conducted in-depth interviews with 14 respondents from a broad range of South African and international CSOs, and analyzed data using thematic analysis. CSO representatives reported disappointment in response to negative trial results, but acknowledged such outcomes as inherent to clinical research. Respondents indicated that in theory negative trial results seem likely to impact on willingness to participate in future trials, but that in practice people in South Africa have continued to volunteer. Negative trial results were described as having contributed to improving ethical standards, and to a re-evaluation of the scientific agenda. Such negative results were identified as potentially impacting on funding for trials and engagement activities. Our findings indicate that trial closures may be used constructively to support opportunities for reflection and renewed vigilance in strategies for stakeholder engagement, communicating trial outcomes, and building research literacy among communities; however, these strategies require sustained resources for community engagement and capacity-building.
Graziani, Gina M; Angel, Jonathan B
Introduction The development of an effective therapeutic HIV vaccine that induces immunologic control of viral replication, thereby eliminating or reducing the need for antiretroviral therapy (ART), would be of great value. Besides the obvious challenges of developing a therapeutic vaccine that would generate effective, sustained anti-HIV immunity in infected individuals is the issue of how to best assess the efficacy of vaccine candidates. Discussion This review discusses the various outcome measures assessed in therapeutic HIV vaccine clinical trials involving individuals receiving suppressive ART, with a particular focus on the role of analytical treatment interruption (ATI) as a way to assess the virologic control induced by an immunotherapy. This strategy is critical given that there are otherwise no readily available measures to determine the ability of a vaccine-induced immune response to effectively control HIV replication. The various outcome measures that have been used to assess vaccine efficacy in published therapeutic HIV vaccine clinical trials will also be discussed. Outcome measures have included the kinetics of viral rebound, the new viral set point and changes in the size of the viral reservoir. Clinically relevant outcomes such as the CD4 decline, the time to resume therapy or the time to meet the criterion to resume therapy, the proportion of participants who resume therapy and/or the development of clinical symptoms such as acute retroviral syndrome are also measures of vaccine efficacy. Conclusions Given the lack of consistency between therapeutic HIV vaccine trials in how efficacy is assessed, comparing vaccines has been difficult. It would, therefore, be beneficial to determine the most clinically relevant measure for use in future studies. Other recommendations for future clinical trials also include studying compartments in addition to blood and replacing ATIs with single-copy assays in situations in which the use of an ATI is not ideal
Bourrillon, Antoine; Bingen, Edouard
Given the devastating nature of Neisseria meningitidis disease and emergence of resistant strains prevention through chemoprophylaxis and meningococcal vaccine remains the best approach to control this serious infection. Chemoprophylaxis may limited strictly to the contact subjects. Polysaccharide meningococcal serogroups A, C, Y and W135 should be given less than 10 days to patients with prolonged contact with the index case. Meningococcal C conjugate vaccine constitutes an additional advantage in the prevention of meningococcal meningitis in children < 2 years. High Haemophilus serotype B coverage level led to near-disappearance of H. influenzae serotype b meningitis but chemoprophylaxis remains indicated.
Polonsky, S; Kerr, S; Harris, B; Gaiter, J; Fichtner, R R; Kennedy, M G
High rates of human immunodeficiency virus (HIV) infection among jail and prison inmates suggest that HIV prevention efforts should focus on incarcerated populations. Overcrowding, the high prevalence of injection drug use, and other high-risk behaviors among inmates create a prime opportunity for public health officials to affect the course of the HIV epidemic if they can remedy these problems. Yet, along with the opportunity, there are certain obstacles that correctional institutions present to public health efforts. The various jurisdictions have differing approaches to HIV prevention and control. Whether testing should be mandatory or voluntary, whether housing should be integrated or segregated by HIV serostatus, and whether condoms, bleach, or clean needles should be made available to the prisoners, are questions hotly debated by public health and correctional officials. Even accurate assessment of risk-taking within the institutions leads to controversy, as asking questions could imply acceptance of the very behaviors correctional officials are trying to prevent. Education and risk-reduction counseling are the least controversial and most widely employed modes of prevention, but the effectiveness of current prevention efforts in reducing HIV transmission in this high-risk population is largely undetermined.
Polonsky, S; Kerr, S; Harris, B; Gaiter, J; Fichtner, R R; Kennedy, M G
High rates of human immunodeficiency virus (HIV) infection among jail and prison inmates suggest that HIV prevention efforts should focus on incarcerated populations. Overcrowding, the high prevalence of injection drug use, and other high-risk behaviors among inmates create a prime opportunity for public health officials to affect the course of the HIV epidemic if they can remedy these problems. Yet, along with the opportunity, there are certain obstacles that correctional institutions present to public health efforts. The various jurisdictions have differing approaches to HIV prevention and control. Whether testing should be mandatory or voluntary, whether housing should be integrated or segregated by HIV serostatus, and whether condoms, bleach, or clean needles should be made available to the prisoners, are questions hotly debated by public health and correctional officials. Even accurate assessment of risk-taking within the institutions leads to controversy, as asking questions could imply acceptance of the very behaviors correctional officials are trying to prevent. Education and risk-reduction counseling are the least controversial and most widely employed modes of prevention, but the effectiveness of current prevention efforts in reducing HIV transmission in this high-risk population is largely undetermined. PMID:7938381
Johnson, Blair T.; Redding, Colleen A.; DiClemente, Ralph J.; Mustanski, Brian S.; Dodge, Brian M.; Sheeran, Paschal; Warren, Michelle R.; Zimmerman, Rick S.; Fisher, William A.; Conner, Mark T.; Carey, Michael P.; Fisher, Jeffrey D.; Stall, Ronald D.; Fishbein, Martin
HIV is transmitted through dyadic exchanges of individuals linked in transitory or permanent networks of varying sizes. To optimize prevention efficacy, a complementary theoretical perspective that bridges key individual level elements with important network elements can be a foundation for developing and implementing HIV interventions with outcomes that are more sustainable over time and have greater dissemination potential. Toward that end, we introduce a Network-Individual-Resource (NIR) model for HIV prevention that recognizes how exchanges of resources between individuals and their networks underlies and sustains HIV-risk behaviors. Individual behavior change for HIV prevention, then, may be dependent on increasing the supportiveness of that individual's relevant networks for such change. Among other implications, an NIR model predicts that the success of prevention efforts depends on whether the prevention efforts (1) prompt behavior changes that can be sustained by the resources the individual or their networks possess; (2) meet individual and network needs and are consistent with the individual's current situation/developmental stage; (3) are trusted and valued; and (4) target high HIV-prevalence networks. PMID:20862606
Gowda, Charitha; McKittrick, Noah; Kim, Deborah; Kappes, Rosemarie A.; Lo Re, Vincent; Tebas, Pablo
Introduction. HIV-infected individuals demonstrate lower immunogenicity to the influenza vaccine, despite immunologic and virologic control of HIV infection. Obesity has been previously shown to be associated with diminished antibody responses to other vaccines in HIV-uninfected persons. However, no studies have examined if obesity is associated with diminished protective immune response to influenza vaccination among HIV-infected persons on antiretroviral therapy (ART). Methods. We performed a retrospective analysis of immunogenicity data from a clinical trial of inactivated, trivalent influenza vaccine. The primary endpoint was the proportion of participants with seroconversion, defined as >4-fold increase in anti-hemagglutinin antibody titers after vaccination. Secondary endpoints were the proportion of participants with seroprotection (defined as antibody titers of ≥1 : 40) and geometric mean hemagglutination inhibition antibody titers. Results. Overall, 48 (27%) participants were obese (body mass index ≥ 30 kg/m2). Seroconversion rates were comparable between obese and nonobese subjects for all three vaccine strains. Further, postvaccination geometric mean titers did not differ by body mass index category. Conclusion. Obesity was not associated with diminished antibody response to influenza vaccination in a sample of healthy HIV-infected persons. PMID:26576297
Gowda, Charitha; McKittrick, Noah; Kim, Deborah; Kappes, Rosemarie A; Lo Re, Vincent; Tebas, Pablo
Introduction. HIV-infected individuals demonstrate lower immunogenicity to the influenza vaccine, despite immunologic and virologic control of HIV infection. Obesity has been previously shown to be associated with diminished antibody responses to other vaccines in HIV-uninfected persons. However, no studies have examined if obesity is associated with diminished protective immune response to influenza vaccination among HIV-infected persons on antiretroviral therapy (ART). Methods. We performed a retrospective analysis of immunogenicity data from a clinical trial of inactivated, trivalent influenza vaccine. The primary endpoint was the proportion of participants with seroconversion, defined as >4-fold increase in anti-hemagglutinin antibody titers after vaccination. Secondary endpoints were the proportion of participants with seroprotection (defined as antibody titers of ≥1 : 40) and geometric mean hemagglutination inhibition antibody titers. Results. Overall, 48 (27%) participants were obese (body mass index ≥ 30 kg/m(2)). Seroconversion rates were comparable between obese and nonobese subjects for all three vaccine strains. Further, postvaccination geometric mean titers did not differ by body mass index category. Conclusion. Obesity was not associated with diminished antibody response to influenza vaccination in a sample of healthy HIV-infected persons.
...) Enhancing Hepatitis Prevention Treatment and Care in the United States; (2) Integrating HIV Prevention and..., CDC, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, 1600 Clifton Road,...
Cason, Cari; Orrock, Nan; Schmitt, Karla; Tesoriero, James; Lazzarini, Zita; Sumartojo, Esther
HIV and sexually transmitted diseases (STDs) are major public health problems in the United States. Since the start of the epidemic, nearly 800,000 persons have been reported with AIDS, and approximately 900,000 Americans are currently living with HIV infection. Each year, 15 million people in the United States become infected with one or more STDs. The direct and indirect costs of the major STDs--not including HIV infection--and their complications are estimated to total at least $10 billion annually. This article underscores the importance of law and other structural factors in the prevention and treatment of HIV and STDs. It describes state-level laws on STD screening, name-based reporting of STDs, name-based reporting of HIV and HIV partner notification implementation, and the impact of laws on STD and HIV risk behaviors and prevention services. More broadly, the article focuses on how the law influences the vulnerability or resilience of persons facing the risk of STDs, HIV infection, or AIDS.
Gorringe, Andrew R; Pajón, Rolando
Serogroup B meningococcal (MenB) disease remains a serious public health problem for which a cross-protective vaccine effective against a wide range of MenB isolates has not been available. Novartis Vaccines has developed a vaccine for the prevention of MenB disease that contains four antigenic components: factor H binding protein (fHbp), neisserial adhesin A (NadA), Neisseria heparin binding antigen (NHBA) and outer membrane vesicles from a New Zealand epidemic strain (which provides PorA). This vaccine has been submitted for regulatory review in Europe so it is timely to review the design of the vaccine, results to date in clinical studies and the potential strain coverage provided by the vaccine. It is also critical to discuss the key issues for the long-term success of the vaccine which include strain coverage, potential persistence of protection, potential effects on carriage of MenB strains, potential for escape mutants and cost effectiveness.
Geary, Cynthia Waszak; Burke, Holly McClain; Castelnau, Laure; Neupane, Shailes; Sall, Yacine Ba; Wong, Emily; Tucker, Heidi Toms
In 2002 MTV launched a global multicomponent HIV prevention campaign, "Staying Alive," reaching over 166 countries worldwide. An evaluation of this campaign focused on three diverse sites: Kathmandu, Nepal; São Paulo, Brazil; and Dakar, Senegal. Data were collected before and after campaign implementation through population-based household surveys. Using linear regression techniques, our evaluation examined the effects of campaign exposure on interpersonal communication about HIV and the effects of campaign exposure and interpersonal communication on beliefs about HIV prevention. We found a consistent positive effect of exposure on interpersonal communication across all sites, though there were differences among sites with regard to whom the respondent talked about HIV. We also found a consistent positive effect of exposure on HIV prevention beliefs across sites when interpersonal communication was simultaneously entered into the model. Finally, in two sites we found a relationship between interpersonal communication and HIV prevention beliefs, controlling for exposure, though again, the effects differed by the type of person the communication was with. These similar findings in three diverse sites provide ecological validity of the findings that "Staying Alive" promoted interpersonal communication and influenced young people's beliefs about HIV prevention in a positive way, evidence for the potential of a global media campaign to have an impact on social norms.
Murdaca, Giuseppe; Orsi, Andrea; Spanò, Francesca; Faccio, Valeria; Puppo, Francesco; Durando, Paolo; Icardi, Giancarlo; Ansaldi, Filippo
Systemic Lupus Erythematosus (SLE) is characterized by abnormal autoantibody production and clearance. Infections are among the most important causes of morbidity and mortality in SLE patients; they have an increased frequency of severe bacterial and viral infections possibly due to inherited genetic and immunologic defects and to immunosuppressive therapies. In addition, infectious agents can switch on lupus disease expression and activity. Among the strategies to reduce the risk of infection, vaccination can be considered the most reliable option. Most vaccines are effective and safe in SLE patients, although in certain cases immunogenicity may be sub-optimal and vaccination can trigger a flare. Although these issues are currently unresolved, the risk benefit balance is in favor for vaccination to reduce the risk of infection in SLE patients. In the present review we discuss the preventive strategies currently recommended to reduce bacterial and viral infections in SLE. PMID:26750996
Omer, Saad B; Salmon, Daniel A; Orenstein, Walter A; deHart, M Patricia; Halsey, Neal
Vaccines are among the most effective prevention tools available to clinicians. However, the success of an immunization program depends on high rates of acceptance and coverage. There is evidence of an increase in vaccine refusal in the United States and of geographic clustering of refusals that results in outbreaks. Children with exemptions from school immunization requirements (a measure of vaccine refusal) are at increased risk for measles and pertussis and can infect others who are too young to be vaccinated, cannot be vaccinated for medical reasons, or were vaccinated but did not have a sufficient immunologic response. Clinicians can play a crucial role in parental decision making. Health care providers are cited as the most frequent source of immunization information by parents, including parents of unvaccinated children. Although some clinicians have discontinued or have considered discontinuing their provider relationship with patients who refuse vaccines, the American Academy of Pediatrics Committee on Bioethics advises against this and recommends that clinicians address vaccine refusal by respectfully listening to parental concerns and discussing the risks of nonvaccination.
Scheibe, A; Drame, F M; Shannon, K
Sex work occurs to meet the demand for sexual services and is a universal phenomenon. In Africa sex work takes many forms and is an important source of income for many women. Yet sex worker reproductive health needs remain largely unmet. The criminalisation of sex work; community and service provider stigma; violence; substance use and limited access to health services and prevention commodities contribute to the high HIV burden evident among female sex workers in Africa. Following UNAIDS' three pillar approach to HIV prevention and sex work we present an overview of current opportunities, barriers and suggestions to improve HIV prevention policy and programming for sex work in Africa. Universal access to a comprehensive package of HIV services is the first pillar. Reproductive health commodities; voluntary and anonymous HIV counselling and testing; treatment of sexually transmitted infections, HIV and opportunistic infections; harm reduction for substance use and psychosocial support services make up the recommended package of services. The second pillar is a sex worker-supportive environment. The inclusion of sex worker programmes within national HIV strategic planning; sex worker-led community mobilisation and the establishment of sex work community networks (comprised of sex workers, health service providers, law enforcers and other stakeholders) enable effective programme implementation and are recommended. The reduction of sex worker vulnerability and addressing structural issues form the final pillar. The decriminalisation of sex work; development of supportive policy; gender equality and economic development are key factors that need to be addressed to increase sex worker resilience. Evidence supports the public health benefit of human rights based approaches to HIV prevention; moralistic and restrictive policy and laws towards sex work are harmful and should be removed. The establishment of these pillars will increase sex worker safety and enhance the
Tambo, Ernest; Yah, Clarence S; Ugwu, Chidiebere E; Olalubi, Oluwasogo A; Wurie, Isatta; Jonhson, Jeannetta K; Ngogang, Jeanne Y
Human immunodeficiency virus (HIV) and the re-emerging Ebola virus disease (EVD) are closely intertwined and remain a persistent public health threat and global challenge. Their origin and rapid transmission and spread have similar boundaries and share overlapping impact characteristics, including related symptoms and other interactions. The controversies and global threat of these viruses require rapid response policy and evidence-based implementation findings. The constraints and dual burden inflicted by Ebola and HIV infections are highly characterized by similar socio-demographics, socio-economic and political factors. EVD has similar effects and burdens to HIV infection. This study seeks to understand EVD in the context of HIV epidemic despite the challenges in developing an effective vaccine against HIV and EVD. Our findings show that early understanding, prevention and treatment of these diseases a global health threat mainly in Africa is important and valuable. The lessons learned so far from HIV and Ebola epidemics are crucial in health programming and execution of rapid response interventions and continued vigilance against EVD before it become another worldwide health menace. Therefore, the current regional West Africa EVD requires strengthening healthcare systems and building preparedness and response capacity. Importantly, appropriate community participation, health education and resilience coupled with deployment of effective novel diagnostic approaches in early warning and surveillance of threats and emerging diseases. Therefore, there is an urgent need to develop novel key strategies are crucial in curbing the constant viral resurgence, persistence transmission dynamics and spread, as well in accelerating Ebola vaccines regimen (immunization) development and national implementation plans in achieving sustained control, and eventual elimination.
Nishiyama, Yasuhiro; Planque, Stephanie; Mitsuda, Yukie; Nitti, Giovanni; Taguchi, Hiroaki; Jin, Lei; Symersky, Jindrich; Boivin, Stephane; Sienczyk, Marcin; Salas, Maria; Hanson, Carl V.; Paul, Sudhir
We describe murine monoclonal antibodies (mAbs) raised by immunization with an electrophilic gp120 analog (E-gp120) expressing the rare ability to neutralize genetically heterologous human immunodeficiency virus (HIV) strains. Unlike gp120, E-gp120 formed covalent oligomers. The reactivity of gp120 and E-gp120 with mAbs to reference neutralizing epitopes was markedly different, indicating their divergent structures. Epitope mapping with synthetic peptides and electrophilic peptide analogs indicated binary recognition of two distinct gp120 regions by anti-E-gp120 mAbs, the 421-433 and 288-306 peptide regions. Univalent Fab and single chain Fv fragments expressed the ability to recognize both peptides. X-ray crystallography of an anti-E-gp120 Fab fragment revealed two neighboring cavities, the typical antigen-binding cavity formed by the complementarity determining regions (CDRs) and another cavity dominated by antibody heavy chain variable (VH) domain framework (FR) residues. Substitution of the FR cavity VH Lys-19 residue by an Ala residue resulted in attenuated binding of the 421-433 region peptide probe. The CDRs and VH FR replacement/silent mutation ratios exceeded the ratio for a random mutation process, suggesting adaptive development of both putative binding sites. All mAbs studied were derived from VH1 family genes, suggesting biased recruitment of the V gene germ line repertoire by E-gp120. The conserved 421-433 region of gp120 is essential for HIV binding to host CD4 receptors. This region is recognized weakly by the FR of antibodies produced without exposure to HIV, but it usually fails to induce adaptive synthesis of neutralizing antibodies. We present models accounting for improved CD4-binding site recognition and broad HIV neutralizing activity of the mAbs, long sought goals in HIV vaccine development.
Chandler-Coley, Rasheeta; Ross, Henry; Ozoya, Oluwatobi; Lescano, Celia; Flannigan, Timothy
Media messages can facilitate the delivery of accurate information related to HIV and sexually transmitted infection. This study's purpose was to examine preexisting media campaigns from the iMPPACS study to assess age-, gender-, and culturally appropriate components identified by African American females who attend historically Black colleges/universities. In 3 separate focus group sessions, 31 Black female college students (M age = 20) viewed 4 vignettes and heard 3 audio-only clips, then ranked and commented on them based on perceived satisfaction with HIV prevention content and appropriateness of delivery. Conventional qualitative analysis using NVivo software was performed until saturation of content was achieved and themes derived. Six major themes emerged and were designated as (a) social media; (b) mirror image; (c) visually dynamic advertisements; (d) the real world; (e) people, place, things; and (f) HIV knowledge. Visually stimulating content (i.e., graphics) was found to be most appealing in marketing HIV prevention, with brief monologue/dialogue from scenarios that resemble daily life. Socially and culturally relevant HIV prevention messages are important to Black college female students. Participants recommended creating short audiovisual messages that encompass familiar contexts like dorm rooms and appealing graphics for HIV health promotion messages, such as emojis. Future audio-only prevention advertisements for this population should use recognizable voices (e.g., celebrities). Finally, messaging should be promoted on open and closed circuit social media platforms.
Gil-Llario, María Dolores; Ballester-Arnal, Rafael; Giménez-García, Cristina; Salmerón-Sánchez, Pedro
The HIV-AIDS remains a public health problem which disproportionally affects women. However, prevention strategies have rarely considered their specific efficacy for them. For this reason, this study examines the differential effectiveness of six intervention elements based on socio-cognitive theories addressing young women. A controlled between-groups design examined the change in risk profile among 167 young Spanish women (mean age 21.3 years old) involved in five sexual risk prevention interventions (informative talk, attitudinal discussion, role-play, fear induction and informative website) and one control non-intervening group (waiting list). Our findings support the differential efficacy of some HIV preventive intervention elements comparing others for women. In particular, the attitudinal discussion stands out followed by the informative talk and the role play. Contrarily, the fear induction component did not reveal relevant improvements. This study provides new evidence related to HIV prevention. Particularly, the higher efficacy of motivational components for these young Spanish women is revealed.
Hudson, C P
Networks of concurrent sexual partnerships may be the primary cause of epidemic spread of HIV-1 in parts of sub-Saharan Africa. This pattern of sexual behaviour increases the likelihood that individuals experiencing primary HIV-1 infection transmit the virus to other persons. Networks of concurrent partnerships are likely to be important in both the early ('epidemic') and late ('endemic') phases of HIV-1 transmission. Interventions should aim to break the sexual networks, whatever the stage of the epidemic. However, prevention of transmission in the endemic phase also requires a greater awareness of early clinical manifestations of HIV-1 infection in the general population. Such awareness, coupled with the availability of condoms and access to HIV-1 testing facilities, may reduce transmission in discordant couples.
Paz-Bailey, Gabriela; Raymond, H Fisher; Lansky, Amy; Mermin, Jonathan
The National HIV Behavioral Surveillance system (NHBS) was designed to monitor HIV prevalence and risk factors for infection among higher-risk individuals, i.e., sexually active men who have sex with men who attend venues, injection drug users who injected in the past 12 months, and heterosexuals living in low socioeconomic urban areas. These groups were selected as priorities for behavioral surveillance since they represent the major HIV transmission routes and the populations with the highest HIV burden. NHBS contributes to the nation's program of HIV surveillance by being the only multi-site population-based system that provides estimates on key HIV prevention measures among high-risk HIV-negative individuals, HIV-positive individuals unaware of their infection, and HIV-positive individuals aware of their infection who are in and out of care. Accurate and precise data on the behaviors in these populations are critical for tracking the epidemic, planning effective responses, and monitoring and evaluating those responses. Reports in this supplement illustrate the uses of NHBS data at the national and local level and reflect ongoing efforts to improve the system and remains essential for characterizing and monitoring the burden of HIV infection and sexual and behavioral risks.
Allen, Susan; Than, Soe; Adams, Elizabeth M.; Graham, Barney S.; Koup, Richard A.; Bailer, Robert T.; Smith, Carol; Dally, Len; Tarragona-Fiol, Tony; Bergin, Philip J.; Hayes, Peter; Ho, Martin; Loughran, Kelley; Komaroff, Wendy; Stevens, Gwynneth; Thomson, Helen; Boaz, Mark J.; Cox, Josephine H.; Schmidt, Claudia; Gilmour, Jill; Nabel, Gary J.; Fast, Patricia
Background We conducted a double-blind, randomized, placebo-controlled Phase I study of a recombinant replication-defective adenovirus type 5 (rAd5) vector expressing HIV-1 Gag and Pol from subtype B and Env from subtypes A, B and C, given alone or as boost following a DNA plasmid vaccine expressing the same HIV-1 proteins plus Nef, in 114 healthy HIV-uninfected African adults. Methodology/Principal Findings Volunteers were randomized to 4 groups receiving the rAd5 vaccine intramuscularly at dosage levels of 1×1010 or 1×1011 particle units (PU) either alone or as boost following 3 injections of the DNA vaccine given at 4 mg/dose intramuscularly by needle-free injection using Biojector® 2000. Safety and immunogenicity were evaluated for 12 months. Both vaccines were well-tolerated. Overall, 62% and 86% of vaccine recipients in the rAd5 alone and DNA prime - rAd5 boost groups, respectively, responded to the HIV-1 proteins by an interferon-gamma (IFN-γ) ELISPOT. The frequency of immune responses was independent of rAd5 dosage levels. The highest frequency of responses after rAd5 alone was detected at 6 weeks; after DNA prime - rAd5 boost, at 6 months (end of study). At baseline, neutralizing antibodies against Ad5 were present in 81% of volunteers; the distribution was similar across the 4 groups. Pre-existing immunity to Ad5 did not appear to have a significant impact on reactogenicity or immune response rates to HIV antigens by IFN-γ ELISPOT. Binding antibodies against Env were detected in up to 100% recipients of DNA prime - rAd5 boost. One volunteer acquired HIV infection after the study ended, two years after receipt of rAd5 alone. Conclusions/Significance The HIV-1 rAd5 vaccine, either alone or as a boost following HIV-1 DNA vaccine, was well-tolerated and immunogenic in African adults. DNA priming increased the frequency and magnitude of cellular and humoral immune responses, but there was no effect of rAd5 dosage on immunogenicity endpoints. Trial
Eide, Arne Henning; Schür, Clare; Ranchod, Chitra; Rohleder, Poul; Swartz, Leslie; Schneider, Marguerite
The main research question in this article is how access to information about HIV/AIDS and level of HIV/AIDS prevention related knowledge are distributed among disabled people, and whether level of knowledge predicts access to HIV/AIDS related services. A survey was carried out among a sample of 285 disabled people from three provinces in South Africa. Analyses of the data revealed that gender and level of education, together with geographical differences, are key predictors for access to information and knowledge about HIV/AIDS among disabled people. For male respondents number of information sources predicts access to voluntary counselling and testing services and HIV testing, while knowledge about prevention predicts access to Voluntary Counselling and Testing centres. Significant gender differences with regards to information, knowledge and access to services highlight the need for gender specific prevention strategies among disabled people.
Rhodes, Corinne M.; Chang, Yuchiao; Regan, Susan; Triant, Virginia A.
Importance The Human Immunodeficiency Virus (HIV) epidemic has evolved, with an increasing non-communicable disease (NCD) burden emerging and need for long-term management, yet there are limited data to help delineate the optimal care model to screen for NCDs for this patient population. Objective The primary aim was to compare rates of NCD preventive screening in persons living with HIV/AIDS (PLWHA) by type of HIV care model, focusing on metabolic/cardiovascular disease (CVD) and cancer screening. We hypothesized that primary care models that included generalists would have higher preventive screening rates. Design Prospective observational cohort study. Setting Partners HealthCare System (PHS) encompassing Brigham & Women’s Hospital, Massachusetts General Hospital, and affiliated community health centers. Participants PLWHA age >18 engaged in active primary care at PHS. Exposure HIV care model categorized as infectious disease (ID) providers only, generalist providers only, or ID plus generalist providers. Main Outcome(s) and Measures(s) Odds of screening for metabolic/CVD outcomes including hypertension (HTN), obesity, hyperlipidemia (HL), and diabetes (DM) and cancer including colorectal cancer (CRC), cervical cancer, and breast cancer. Results In a cohort of 1565 PLWHA, distribution by HIV care model was 875 ID (56%), 90 generalists (6%), and 600 ID plus generalists (38%). Patients in the generalist group had lower odds of viral suppression but similar CD4 counts and ART exposure as compared with ID and ID plus generalist groups. In analyses adjusting for sociodemographic and clinical covariates and clustering within provider, there were no significant differences in metabolic/CVD or cancer screening rates among the three HIV care models. Conclusions There were no notable differences in metabolic/CVD or cancer screening rates by HIV care model after adjusting for sociodemographic and clinical factors. These findings suggest that HIV patients receive similar
Njoku, Ogbonnaya S.; O’Connell, Robert J.; Shutt, Ashley L. W.; Malia, Jennifer A.; Heipertz, Richard A.; Tovanabutra, Sodsai; Milazzo, Mark J.; Akintunde, Gideon Akindiran; Alabi, Abraham S.; Suleiman, Aminu; Ogundeji, Amos A.; Kene, Terfa S.; Nelson, Robbie; Ayemoba, Ojor R.; Singer, Darrell E.; Robb, Merlin L.; Peel, Sheila A.; Michael, Nelson L.
Development of a globally effective HIV-1 vaccine will need to encompass Nigeria, one of the hardest hit areas, with an estimated 3.2 million people living with HIV. This cross-sectional Institutional Review Board (IRB) approved study was conducted in 2009–12 at four market sites and two highway settlements sites in Nigeria to identify and characterize populations at high risk for HIV; engage support of local stakeholders; and assess the level of interest in future vaccine studies. Demographic, HIV risk data were collected by structured interviewer-administered questionnaires. Blood samples were tested on site by HIV rapid diagnostic tests, followed by rigorous confirmatory testing, subtype evaluation and testing for HBV and HCV markers in a clinical reference laboratory. Of 3229 study participants, 326 were HIV infected as confirmed by Western Blot or RNA, with a HIV prevalence of 15.4%-23.9% at highway settlements and 3.1%-9.1% at market sites. There was no observable correlation of prevalence of HIV-1 (10.1%) with HBV (10.9%) or HCV (2.9%). Major HIV-1 subtypes included CRF02_AG (37.5%); G (27.5%); G/CRF02_AG (25.9%); and non-typeable (8.9%), with 0.3% HIV-2. Univariate analysis found age, gender, marital status, level of education, and sex under substance influence as significant risk factors for HIV (p<0.001). Educating and winning the trust of local community leadership ensured high level of participation (53.3–77.9%) and willingness to participate in future studies (95%). The high HIV prevalence and high risk of HIV infection at highway settlement and mammy markets make them well suited for targeting future vaccine trials in Nigeria. PMID:27936236
Njoku, Ogbonnaya S; Manak, Mark M; O'Connell, Robert J; Shutt, Ashley L W; Malia, Jennifer A; Heipertz, Richard A; Tovanabutra, Sodsai; Milazzo, Mark J; Akintunde, Gideon Akindiran; Alabi, Abraham S; Suleiman, Aminu; Ogundeji, Amos A; Kene, Terfa S; Nelson, Robbie; Ayemoba, Ojor R; Singer, Darrell E; Robb, Merlin L; Peel, Sheila A; Michael, Nelson L
Development of a globally effective HIV-1 vaccine will need to encompass Nigeria, one of the hardest hit areas, with an estimated 3.2 million people living with HIV. This cross-sectional Institutional Review Board (IRB) approved study was conducted in 2009-12 at four market sites and two highway settlements sites in Nigeria to identify and characterize populations at high risk for HIV; engage support of local stakeholders; and assess the level of interest in future vaccine studies. Demographic, HIV risk data were collected by structured interviewer-administered questionnaires. Blood samples were tested on site by HIV rapid diagnostic tests, followed by rigorous confirmatory testing, subtype evaluation and testing for HBV and HCV markers in a clinical reference laboratory. Of 3229 study participants, 326 were HIV infected as confirmed by Western Blot or RNA, with a HIV prevalence of 15.4%-23.9% at highway settlements and 3.1%-9.1% at market sites. There was no observable correlation of prevalence of HIV-1 (10.1%) with HBV (10.9%) or HCV (2.9%). Major HIV-1 subtypes included CRF02_AG (37.5%); G (27.5%); G/CRF02_AG (25.9%); and non-typeable (8.9%), with 0.3% HIV-2. Univariate analysis found age, gender, marital status, level of education, and sex under substance influence as significant risk factors for HIV (p<0.001). Educating and winning the trust of local community leadership ensured high level of participation (53.3-77.9%) and willingness to participate in future studies (95%). The high HIV prevalence and high risk of HIV infection at highway settlement and mammy markets make them well suited for targeting future vaccine trials in Nigeria.
Li, Hua; Liu, Zu-Qiang; Ding, Jian; Chen, Ying-Hua
Monoclonal antibody 2F5 recognizing ELDKWA-epitope on HIV-1 gp41 has significant neutralization potency against 90% of the investigated viruses of African, Asia, American and European strains, but antibodies responses to ELDKWA-epitope in HIV-1 infected individuals were very low. Based on the epitope-vaccine strategy suggested by us, a recombinant glutathione S-transferase (GST) fusion protein (GST-MELDKWAGELDKWAGELDKWAVDIGPGRAFYGPGRAFYGPGRAFY) as vaccine antigen containing three repeats of neutralizing epitope ELDKWA on gp41 and GPGRAFY on gp120 was designed and expressed in Escherichia coli. After vaccination course, the recombinant multi-epitope vaccine could induce high levels of predefined multi-epitope-specific antibodies in mice. These antibodies in sera could bind to both neutralizing epitopes on gp41 peptide, V3 loop peptide and recombinant soluble gp41 (aa539-684) in ELISA assay (antisera dilution: 1:1,600-25,600), while normal sera did not. Moreover, these antibodies in sera could recognize the CHO-WT cells which expressed HIV-1 envelope glycoprotein on the cell surfaces, indicating that the predefined epitope-specific antibodies could recognize natural envelope protein of HIV-1 though these antibodies were induced by recombinant multi-epitope-vaccine. These experimental results suggested a possible way to develop recombinant multi-epitope vaccine inducing multi-antiviral activities against HIV-1.
Pettifor, Audrey; Bekker, Linda-Gail; Hosek, Sybil; DiClemente, Ralph; Rosenberg, Molly; Bull, Sheana; Allison, Susannah; Delany-Moretlwe, Sinead; Kapogiannis, Bill G.; Cowan, Frances
Objective To review the current state of knowledge on the prevention of sexual transmission of HIV in adolescents and to highlight existing gaps and priority areas for future research. Background A disproportionate burden of HIV infections falls on adolescents, a developmental stage marked by unique neural, biological, and social transition. Successful interventions are critical to prevent the spread of HIV in this vulnerable population. Methods We summarized the current state of research on HIV prevention in adolescents by providing examples of successful interventions and best practices, and highlighting current research gaps. Results Adolescent interventions fall into three main categories: biomedical, behavioral, and structural. The majority of current research has focused on individual behavior change, while promising biomedical and structural interventions have been largely understudied in adolescents. Combination prevention interventions may be particularly valuable to this group. Conclusions Adolescents have unique needs with respect to HIV prevention and, thus, interventions should be designed to most effectively reach this population with information and services that will be relevant to them. PMID:23764629
Schooley, Robert T.; Spritzler, John; Wang, Hongying; Lederman, Michael M.; Havlir, Diane; Kuritzkes, Daniel R.; Pollard, Richard; Battaglia, Cathy; Robertson, Michael; Mehrotra, Devan; Casimiro, Danilo; Cox, Kara; Schock, Barbara
Background HIV-1 specific cellular immunity contributes to control of HIV-1 replication. HIV-1 infected volunteers on antiretroviral therapy received a replication defective Ad5 HIV-1 gag vaccine in a randomized, blinded therapeutic vaccination study. Methods HIV-1-infected vaccine or placebo recipients underwent a 16-wk analytical treatment interruption (ATI). The log10 HIV-1 RNA at the ATI set point and time averaged area under the curve (TA-AUC) served as co-primary endpoints. Immune responses were measured by intracellular cytokine staining and CFSE dye dilution. Results Vaccine benefit trends were seen for both primary endpoints, but did not reach a pre-specified p ≤ 0.025 level of significance. The estimated shift in TA-AUC and set point were 0.24 (unadjusted p=0.04) and 0.26 (unadjusted p=0.07) log10 copies lower in the vaccine than in the placebo arm. HIV-1 gag-specific CD4+ interferon-γ producing cells were an immunologic correlate of viral control. Conclusion The vaccine was generally safe and well tolerated. Despite a trend favoring viral suppression among vaccine recipients, differences in HIV-1 RNA levels did not meet the pre-specified level of significance. Induction of HIV-1 gag-specific CD4 cells correlated with control of viral replication in vivo. Future immunogenicity studies should require a substantially higher immunogenicity threshold before an ATI is contemplated. PMID:20662716
Sadanand, Saheli; Suscovich, Todd J; Alter, Galit
HIV-1 poses immense immunological challenges to the humoral immune response because of its ability to shield itself and replicate and evolve rapidly. Although most currently licensed vaccines provide protection via the induction of antibodies (Abs) that can directly block infection ( 1 ), 30 years of HIV-1 vaccine research has failed to successfully elicit such Abs against globally relevant HIV strains. However, mounting evidence suggests that these broadly neutralizing antibodies (bNAbs) do emerge naturally in a significant fraction of infected subjects, albeit after years of infection, indicating that these responses can be selected naturally by the immune response but take long periods of time to evolve. We review the basic structural characteristics of broadly neutralizing antibodies and how they recognize the virus, and we discuss new vaccination strategies that aim to mimic natural evolution to guide B cells to produce protective Abs against HIV-1.
Cardozo, Timothy; Wang, Shixia; Jiang, Xunqing; Kong, Xiang-Peng; Hioe, Catarina; Krachmarov, Chavdar
We designed synthetic, epitope-focused immunogens that preferentially display individual neutralization epitopes targeted by cross-subtype anti-HIV V3 loop neutralizing monoclonal antibodies (mAbs). Vaccination of rabbits with these immunogens resulted in the elicitation of distinct polyclonal serum Abs that exhibit cross-subtype neutralization specificities mimicking the mAbs that guided the design. Our results prove the principle that a predictable range of epitope-specific polyclonal cross-subtype HIV-1 neutralizing Abs can be intentionally elicited in mammals by vaccination. The precise boundaries of the epitopes and conformational flexibility in the presentation of the epitopes in the immunogen appeared to be important for successful elicitation. This work may serve as a starting point for translating the activities of human broadly neutralizing anti-HIV-1 monoclonal antibodies (bNAbs) into matched immunogens that can contribute to an efficacious HIV-1 vaccine.
Bärnighausen, Till; Bloom, David E; Humair, Salal
The HIV Prevention Trials Network (HPTN) 052 study, which showed the effectiveness of antiretroviral treatment in reducing HIV transmission, has been hailed as a "game changer" in the fight against HIV, prompting calls for scaling up treatment as prevention (TasP). However, it is unclear how TasP can be financed, given flat-lining support for global HIV programs. We assess whether TasP is indeed a game changer or if comparable benefits are obtainable at similar or lower cost by increasing coverage of medical male circumcision (MMC) and antiretroviral treatment (ART) at CD4 <350/μL. We develop a new mathematical model and apply it to South Africa, finding that high ART coverage combined with high MMC coverage provides approximately the same HIV incidence reduction as TasP, for $5 billion less over 2009-2020. MMC outperforms ART significantly in cost per infection averted ($1,096 vs. $6,790) and performs comparably in cost per death averted ($5,198 vs. $5,604). TasP is substantially less cost effective at $8,375 per infection and $7,739 per death averted. The prevention benefits of HIV treatment are largely reaped with high ART coverage. The most cost-effective HIV prevention strategy is to expand MMC coverage and then scale up ART, but the most cost-effective HIV-mortality reduction strategy is to scale up MMC and ART jointly. TasP is cost effective by commonly used absolute benchmarks but it is far less cost effective than MMC and ART. Given South Africa's current annual ART spending, the $5 billion in savings offered by MMC and ART over TasP in the next decade, for similar health benefits, challenges the widely hailed status of TasP as a game changer.
Kaufman, D R; Barouch, D H
Many pathogens use mucosal surfaces to enter and propagate within the host, making particularly desirable vaccines that target immune responses specifically to mucosal compartments. The majority of mucosal vaccine design strategies to date have been empirical in nature. However, an emerging body of basic immunological knowledge is providing new insights into the regulation of tissue-specific lymphocyte trafficking and differentiation. These insights afford the opportunity for the rational design of vaccines that focus immune responses at mucosal surfaces. Mucosal cellular immunity may prove critical for protection in the context of HIV infection, and thus there has been considerable interest in developing vaccines that target HIV-specific cellular immune responses to the gastrointestinal and vaginal mucosa. However, the optimal strategies for eliciting mucosal cellular immune responses through vaccination remain to be determined. Here, we review both recent vaccine studies and emerging paradigms from the basic immunological literature that are relevant to the elicitation of potent and protective mucosal cellular immune memory. Increasing the synergy between these avenues of research may afford new opportunities for mucosal vaccine design. PMID:19604255
Valdiserri, Ronald O; Ogden, Lydia O; Janssen, Robert S; Onorato, Ida; Martin, Tonya
Reducing new HIV infections in the United States requires allocating public resources to interventions that will have the greatest impact on reducing the number of new infections. We report on the organizational experience of a federal agency's efforts to align its HIV prevention resources to reflect the specific priorities of a five-year strategic plan that has as its goal a fifty percent reduction in the number of annual HIV infections nationwide. Structural and other impediments encountered during the alignment process, and the steps taken to minimize their impact are described, adding to the empirical data base of strategic planning experiences in the public sector.
Card, Josefina J.; Newman, Emily N.; Golden, Rachel E.; Kuhn, Tamara; Lomonaco, Carmela
This paper describes the development, content, and capabilities of the online Global HIV Archive (GHA). With the goal of facilitating widespread adaptation and appropriate use of efficacious HIV prevention programs throughout the globe, GHA has: first, expanded and updated the search for HIV prevention programs originating in low-resource countries; second, identified those meritorious HIV prevention programs meeting established efficacy criteria of technical merit, replicability, and positive outcomes; third, prepared both implementation and evaluation materials from the efficacious programs for public use; fourth, developed interactive wizards or capacity-building tools to facilitate appropriate program selection, implementation, and adaptation; and, fifth, made the efficacious programs and accompanying wizards available to health practitioners throughout the globe in both printed and online formats. PMID:24563820
Group A beta hemolytic streptococcus (GAS), the organism which initiates rheumatic fever (RF) continues to be sensitive to penicillin. However, penicillin cannot prevent RF if the preceding sore throat is asymptomatic in more than 70 percent children. Prevention of rheumatic fever (RF) may be possible only with the use of a vaccine. Efforts to design a vaccine based on emm gene identification of GAS, M-protein going on for more than 40 years, is unlikely to succeed. M-protein is strain specific. Infection with one strain does not provide immunity from infection with another strain. Based on the emm gene identification, of 250 or more identified strains of GAS, the distribution is heterogenous and keeps changing. The M-protein gene sequence of the organism tends to mutate. A vaccine prepared from available strains may not be effective against a strain following mutation. Lethal toxic shock syndrome due to GAS infection has been described with organisms without identifiable or functional M-protein. M-protein has been excluded as the antigen responsible for acute glomerulonephritis (GN). Therefore M-protein plays no role in one suppurative (toxic shock syndrome) and one non-suppurative (acute GN) manifestation due to GAS infection. Lastly there is no direct evidence to indicate that M-protein is involved in inducing RF. The role of M-protein and the GAS component resulting in the suppurative manifestations of GAS infections like pyoderma, septic arthritis or necrotizing fasciitis etc is unknown. For a vaccine to be effective, an epitope of the streptococcus which is stable and uniformly present in all strains, needs to be identified and tested for its safety and efficacy. The vaccine if and when available is expected to prevent GAS infection. Preventing GAS infection will prevent all the suppurative as well as non-suppurative manifestations including RF.
Principi, Nicola; Esposito, Susanna
Community-acquired pneumonia (CAP) places a considerable burden on society. A substantial number of pediatric and adult CAP cases are due to Streptococcus pneumoniae, but fortunately there are effective vaccines available that have a significant impact on CAP-related medical, social, and economic problems. The main aim of this paper is to evaluate the published evidence concerning the impact of pneumococcal vaccines on the prevention of CAP in children and adults. Available data indicate that pneumococcal conjugate vaccines (PCVs) are effective in children, reducing all-cause CAP cases and bacteremic and nonbacteremic CAP cases. Moreover, at least for PCV7 and PCV13, vaccination of children is effective in reducing the incidence of CAP among adults. Recently use of PCV13 in adults alone or in combination with the pneumococcal polysaccharide vaccine has been suggested and further studies can better define its effectiveness in this group of subjects. The only relevant problem for PCV13 is the risk of a second replacement phenomenon, which might significantly reduce its real efficacy in clinical practice. Protein-based pneumococcal vaccines might be a possible solution to this problem. PMID:28029140
Jin, Xia; Morgan, Cecilia; Yu, Xuesong; DeRosa, Stephen; Tomaras, Georgia D; Montefiori, David C; Kublin, James; Corey, Larry; Keefer, Michael C
Plasmid DNA vaccines have been licensed for use in domesticated animals because of their excellent immunogenicity, but none have yet been licensed for use in humans. Here we report a retrospective analysis of 1218 healthy human volunteers enrolled in 10 phase I clinical trials in which DNA plasmids encoding HIV antigens were administered. Elicited T-cell immune responses were quantified by validated intracellular cytokine staining (ICS) stimulated with HIV peptide pools. HIV-specific binding and neutralizing antibody activities were also analyzed using validated assays. Results showed that, in the absence of adjuvants and boosting with alternative vaccines, DNA vaccines elicited CD8+ and CD4+ T-cell responses in an average of 13.3% (95% CI: 9.8-17.8%) and 37.7% (95% CI: 31.9-43.8%) of vaccine recipients, respectively. Three vaccinations (vs. 2) improved the proportion of subjects with antigen-specific CD8+ responses (p=0.02), as did increased DNA dosage (p=0.007). Furthermore, female gender and participants having a lower body mass index were independently associated with higher CD4+ T-cell response rate (p=0.001 and p=0.008, respectively). These vaccines elicited minimal neutralizing and binding antibody responses. These findings of the immunogenicity of HIV DNA vaccines in humans can provide guidance for future clinical trials.
Greenberg, David P; Robertson, Corwin A; Gordon, Daniel M
Influenza and dengue are viral illnesses of global public health importance, especially among children. Accordingly, these diseases have been the focus of efforts to improve their prevention and control. Influenza vaccination offers the best protection against clinical disease caused by strains contained within the specific year's formulation. It is not uncommon for there to be a mismatch between vaccine strains and circulating strains, particularly with regards to the B lineages. For more than a decade, two distinct lineages of influenza B (Yamagata and Victoria) have co-circulated in the US with varying frequencies, but trivalent influenza vaccines contain only one B-lineage strain and do not offer adequate protection against the alternate B-lineage. Quadrivalent influenza vaccines (QIVs), containing two A strains (H1N1 and H3N2) and two B strains (one from each lineage) have been developed to help protect against the four strains predicted to be the most likely to be circulating. The QIV section of this article discusses epidemiology of pediatric influenza, importance of influenza B in children, potential benefits of QIV, and new quadrivalent vaccines. In contrast to influenza, a vaccine against dengue is not yet available in spite of many decades of research and development. A global increase in reports of dengue fever (DF) and its more severe presentations, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), suggest that US physicians will increasingly encounter patients with this disease. Similarities of the early signs and symptoms of influenza and dengue and the differences in disease management necessitates a better understanding of the epidemiology, clinical presentation, management, and prevention of DF by US physicians, including pediatricians. The article also provides a brief overview of dengue and discusses dengue vaccine development.
... and Care in the United States Through the HIV Care Continuum Initiative #0; #0; #0; Presidential... Improvements in HIV Prevention and Care in the United States Through the HIV Care Continuum Initiative By the... increasing the use of evidence-based approaches to prevention and care among populations and in regions...
...: National HIV Program for Enhanced HIV/AIDS Screening and Engagement in Care Announcement Type: New. Funding... applications for the Office of Clinical and Preventive Services: National HIV Program for Enhanced HIV/AIDS... Syndrome (HIV/ AIDS) Program serves as the primary source for national advocacy, policy development,...
Background HIV trans-activator protein (Tat) is the crucial factor to control HIV transcription, and is usually considered as an important immunogen for the design of HIV vaccine. Recent studies reported some special bio-activities of Tat protein on immunoregulation. However, to date, few studies have focused on exploring the effects of Tat expression plasmid (pTat) on regulating the immune responses induced by HIV DNA vaccines. In this study, our main objective is to investigate the immunoregulation mediated by pTat in mice. Methods Four gene-coding plasmids (pTat, pGag, pEnv and pPol) were constructed, and the gene expression was detected by western blot method. The effects of pTat on regulating the immune responses to antigens Gag, Env, Pol were assessed by enzyme-linked immunospot and enzyme-linked immunosorbent assay. The data was analysed by one-way analysis of variance. Results After two immunizations, mice vaccinated with antigen expressing plasmid (pGag, pEnv or pPol) plus pTat exhibited significantly stronger IFN-gamma response than that vaccinated with the corresponding antigen alone. Moreover, mice receiving two injections of antigen plus pTat exhibited the same strong IFN-gamma response as those receiving three injections of antigen alone did. Furthermore, addition of pTat not only induced a more balanced Th1 and Th2 response, but also broadened IgG subclass responses to antigens Gag and Pol. Conclusion pTat exhibited the appreciable effects on modulating immune responses to HIV antigens Gag, Env and Pol, providing us interesting clues on how to optimize HIV DNA vaccine. PMID:24073803
Verma, Ramesh; Khanna, Pardeep; Prinja, Shankar; Rajput, Meena; Chawla, Suraj; Bairwa, Mohan
Hepatitis B is a disease of the liver caused by Hepatitis B virus (HBV) infection. HBV is transmitted through contact with infected blood or body fluids, unprotected sexual intercourse and the perinatal route but not through casual contact. About two billion people worldwide have been infected with the virus, an estimated 360 million live with chronic infection, and at least 600,000 people die annually from acute or chronic consequences of Hepatitis B, such that Hepatitis B is a major public health problem worldwide. HBV is 50 to 100 times more infectious than HIV. It has been estimated that, of the 25 million infants born every year in India, over one million run the lifetime risk of developing chronic HBV infection. Every year over 100,000 Indians die due to illnesses related to HBV infection. Following the launch of the Global Alliance for Vaccines and Immunization (GAVI) to intensify National Immunization Programs (NIPs) in developing countries worldwide. World Health Organization (WHO) recommends that Hepatitis B vaccine should be given to all infants. Several cost-effectiveness analyses of inclusion of Hepatitis B vaccine in India's NIP have been performed. These indicate that universal childhood Hepatitis B immunization in India will be highly cost-effective. The Government of India is also supporting planned state programs for introducing new vaccines as part of routine immunization. The current immunization schedule for hepatitis B vaccine includes a dose given as early as possible after birth, preferably within 24 hours for all institutional deliveries because the birth dose of Hepatitis B vaccine is effective in preventing perinatal transmission of Hepatitis B. Irrespective of the birth dose, 3 doses are to be given at 6, 10, 14 weeks at the same time as DPT and OPV.
Karim, Quarraisha Abdool; Baxter, Cheryl
The impetus for, and efforts in the past 20 years toward a women-initiated method for preventing sexual transmission of HIV has been previously well described. To date, four classes of topical agents categorized by mechanism of action as: surfactants, buffers, cell entry blockers and antiretroviral agents have undergone advanced clinical testing. Thus far, only coitally linked use of 1% tenofovir gel has demonstrated moderate effectiveness in preventing HIV and HSV-2 infection and has generated renewed hope for microbicide development. Studies of new antiviral agents, novel delivery mechanisms and combination/multipurpose products that address challenges of adherence and enhance the effectiveness of tenofovir gel are already underway to further enhance sexual and reproductive health needs of men and women and efforts to prevent HIV infection.
Stewart, Angela; Fasciano, John; Brown, Larry K.
Objective To conduct a critical review of all HIV prevention intervention studies conducted with adolescents in juvenile justice settings to inform future intervention development. Method PubMed and PsycInfo database searches were conducted for peer-reviewed, published HIV prevention intervention studies with juvenile offenders. Results Sixteen studies were identified (N = 3,700 adolescents). Half of the projects utilized rigorous methodologies to determine intervention effect on behavior change, such as conducting a randomized controlled trial (n = 8). Nine studies reported behaviors at least 3 months post-intervention and five out of nine showed decreases in sexual risk behavior. Conclusions Several HIV prevention programs with juvenile offenders have led to sexual risk reduction, although effect sizes are modest. Most existing programs have neglected to address the impact of family, mental health, and substance use on HIV risk. More work is needed to develop evidence-based interventions that include HIV prevention strategies relevant and appropriate for the juvenile justice setting. PMID:19741021
Flynn, Patricia M.; Cunningham, Coleen K.; Rudy, Bret; Wilson, Craig M.; Kapogiannis, Bill; Worrell, Carol; Bethel, James; Monte, Dina; Bojan, Kelly
Background HIV-infected youth are at risk of hepatitis B (HBV) infection and should be vaccinated. Previous reports suggest reduced response to standard HBV vaccine regimens. Methods HIV-infected youth, age 12 to <25 years, were randomly assigned to one of three treatment arms: Arm 1: Engerix B®, 20 mcg HBsAg; Arm 2: Engerix B®, 40 mcg; and Arm 3: Twinrix®, 20mcg HBsAg combined with 720 ELU hepatitis A antigen. Vaccines were administered at weeks 0, 4 and 24. Results Characteristics of evaluable patients (n=336) at entry were similar in the study arms. At enrollment, median CD4+ T-cell count was 460 cells/mm3 (IQR: 305 to 668); 13% were < 200 cells/mm3. Among Engerix B®, 20 mcg recipients, 60.4% responded to vaccine (HBsAb ≥ 10 IU/mL at week 28). Improved vaccine response was seen in recipients of Engerix B®, 40 mcg, (73.2%, vs. Arm 1, p=0.04) and Twinrix® (75.4%, vs. Arm 1, p=0.02). In multivariate analysis, only baseline CD4+ T-cell count and study arm were independent predictors of vaccine response. Conclusions In HIV-infected youth, a three dose vaccination regimen with Engerix B®, 40 mcg, or Twinrix® and higher baseline CD4+ T-cell counts were independently associated with improved vaccine response. PMID:21350366
Biomedical research is critical to identifying effective and safe interventions, such as vaccines, microbicides, male circumcision and antiretrovirals, for prevention. Funding for clinical prevention trials is highly competitive and the benchmarks of success ultimately reduce to quickly enrolling a select group of people at risk, keeping them enrolled, and inducing them to be compliant with trial requirements - all at the lowest cost possible. Juxtaposed with this reality is the fact that HIV is situated with poverty, exploitation, assaults on human dignity, and human rights abuses. The result is a complex web of ethical challenges that are socially constructed along lines of wealth and power. While social science research methods are commonly employed to examine such topics, they have played a marginal role in biomedical HIV prevention research. Why? To answer this question, a core set of persistent interlocking social, behavioural and ethical challenges to biomedical HIV prevention research are described. A critique is offered on how the social has been framed relative to the behavioural, ethical and biomedical components. Examples of how this framing has devalued social knowledge are provided, including the conflation of qualitative research with anecdotal reporting, a bias toward brevity and accuracy over external validity, and difficulties in distinguishing between a moral understanding of social norms and achieving a moral outcome when confronted with ethical challenges in research. Lastly, opportunities are identified for enhancing the success of biomedical HIV prevention research through development of a coherent programme of social science research. Recommendations are offered for reframing the social as a valid domain of scientific inquiry in this highly applied and interdisciplinary context. PMID:21968079
Buckheit, Robert W.; Watson, Karen M.; Morrow, Kathleen M.; Ham, Anthony S.
Women comprise almost 50% of the population of people living with HIV and the majority of these women contracted the virus through sexual transmission in monogamous relationships in the developing world. In these environments, where women are not empowered to protect themselves through the negotiation of condom use, effective means of preventing HIV transmission are urgently needed. In the absence of an approved and effective vaccine, microbicides have become the strategy of choice to provide women with the ability to prevent HIV transmission from their infected partners. Topical microbicides are agents specifically developed and formulated for use in either the vaginal or rectal environment that prevent infection by sexually transmitted infectious organisms, including pathogenic viruses, bacteria and fungi. Although a microbicidal product will have many of the same properties as other anti-infective agents and would be similarly developed through human clinical trials, microbicide development bears its own challenges related to formulation and delivery and the unique environment in which the product must act, as well as the requirement to develop a product that is acceptable to the user. Herein, perspectives based on preclinical and clinical microbicide development experience, which have led to an evolving microbicide development algorithm, will be discussed. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010”. PMID:19874851
Spearman, C W N; Sonderup, Mark W
Hepatitis B is a global public health issue, with some 2 billion people having current or past infection. In Africa, 65 million are chronically infected, an estimated 2.5 million of them in South Africa (SA). Hepatitis B and the associated complications of cirrhosis and hepatocellular carcinoma are entirely vaccine preventable. SA was one of the first ten countries in Africa to introduce universal hepatitis B vaccination in April 1995, but has no birth dose or catch-up programme. Although universal infant vaccination in SA has been successful in increasing population immunity to hepatitis B, improvements in terms of implementing protocols to screen all pregnant mothers for hepatitis B surface antigen (HBsAg) and ensuring full hepatitis B coverage, especially in rural areas, is justified. The World Health Organization has recommended a birth dose of hepatitis B vaccine in addition to the existing hepatitis B vaccine schedule in order to further decrease the risk of perinatal transmission. We recommend that SA implement a birth-dose vaccine into the existing schedule to attenuate the risk of perinatal transmission, prevent breakthrough infections and decrease HBsAg carriage in babies born to HIV-positive mothers.
Ferrantelli, Flavia; Buttò, Stefano; Cafaro, Aurelio; Wahren, Britta; Ensoli, Barbara
The need for an effective HIV/AIDS vaccine is imperative to halt a pandemic that involves more than 40 million individuals worldwide as of 2005 and is causing enormous socio-economic losses, especially in developing countries (DC). The overall failure of more than two decades of HIV vaccine research justifies the demands for a concerted effort for the rapid development of new and efficacious vaccines against HIV/AIDS. In this context, building international collaborative networks is a must for speeding up scientific research and optimizing the use of funding in a synergistic fashion, as resources for HIV/AIDS are limited and do not involve most of the biggest Pharmas that are more interested in drug discovery. The AIDS Vaccine Integrated Project (AVIP) consortium is an example of synergistic partnership of international European Union and DC experts with a common research goal. AVIP is a European Commission-funded (FP-6), consortium-based, 5-year program directed to the fast development of new HIV/AIDS vaccine candidates to be tested in phase I clinical trials in Europe for future advancement to phase II/III testing in DC. To ensure their rapid development, AVIP novel combined vaccines include both regulatory and structural HIV antigens, which have already been tested, as single components, in phase I clinical trials. In particular, such combination vaccines may be superior to earlier vaccine candidates, the vast majority of which are based only on either structural or regulatory HIV products. In fact, the generation of immune responses to both types of viral antigens expressed either early (regulatory products) or late (structural products) during the viral life cycle can maximize immune targeting of both primary or chronic viral infection. Further, the rational design of combined vaccines allows exploitation of immunomodulatory functions of HIV regulatory proteins, which can improve immunity against structural vaccine components. The building of the AVIP
Epps, Patricia H.; Vallenari, Allison
This manual includes all necessary information for implementing the Champs program, which trains older elementary school students or middle/high school students to operate puppets to deliver an HIV/AIDS message to kindergarten through sixth graders. Relying on a peer approach, the Program provides scripted, prerecorded lessons intended to reach…
Thomas, Stephen J; Endy, Timothy P
The dengue viruses (DENV) are mosquito-borne flaviviruses which cause a spectrum of clinical disease known as "dengue," and have emerged and re-emerged as a significant global health problem. It is estimated more than 120 countries currently have endemic DENV transmission, 55% of the world's population is at risk of infection, and there are between 70-500 million infections of which 2.1 million are clinically severe resulting in 21,000 deaths annually. By all estimates the global dengue problem will continue to worsen due to the increasing mobility of the population, ecological changes, and the inability to effectively sustain vector control. There are no licensed antivirals or vaccines to treat or prevent dengue. The development and widespread use of a safe and efficacious dengue vaccine is required to significantly reduce the global dengue burden. In this review the authors discuss dengue vaccines currently in the pre-clinical and clinical development pipeline.
Eshleman, Susan H; Hudelson, Sarah E; Redd, Andrew D; Swanstrom, Ronald; Ou, San-San; Zhang, Xinyi Cindy; Ping, Li-Hua; Piwowar-Manning, Estelle; Porcella, Stephen F; Sievers, Matthew F; Martens, Craig A; Bruno, Daniel; Dukhovlinova, Elena; McCauley, Marybeth; Gamble, Theresa; Fogel, Jessica M; Sabin, Devin; Quinn, Thomas C; Gunde, Laurence; Maliwichi, Madalitso; Nhando, Nehemiah; Akelo, Victor; Moyo, Sikhulile; Panchia, Ravindre; Kumarasamy, Nagalingeswaran; Chotirosniramit, Nuntisa; Melo, Marineide Gonçalves de; Pilotto, Jose; Grinsztejn, Beatriz; Mayer, Kenneth; Chen, Ying Q; Hughes, James P; Cohen, Myron S
HIV Prevention Trials Network 052 demonstrated that antiretroviral therapy (ART) prevents HIV transmission in serodiscordant couples. HIV from index-partner pairs was analyzed to determine the genetic linkage status of partner infections. Forty-six infections were classified as linked, indicating that the index was the likely source of the partner's infection. Lack of viral suppression and higher index viral load were associated with linked infection. Eight linked infections were diagnosed after the index started ART: 4 near the time of ART initiation and 4 after ART failure. Linked infections were not observed when the index participant was stably suppressed on ART.
Korber, Bette; Fischer, William; Wallstrom, Timothy
An effective AIDS vaccine must control highly diverse circulating strains of HIV-1. Among HIV -I gene products, the envelope (Env) protein contains variable as well as conserved regions. In this report, an informatic approach to the design of T-cell vaccines directed to HIV -I Env M group global sequences was tested. Synthetic Env antigens were designed to express mosaics that maximize the inclusion of common potential Tcell epitope (PTE) 9-mers and minimize the inclusion of rare epitopes likely to elicit strain-specific responses. DNA vaccines were evaluated using intracellular cytokine staining (ICS) in inbred mice with a standardized panel of highly conserved 15-mer PTE peptides. I, 2 and 3 mosaic sets were developed that increased theoretical epitope coverage. The breadth and magnitude ofT-cell immunity stimulated by these vaccines were compared to natural strain Env's; additional comparisons were performed on mutant Env's, including gpl60 or gpl45 with or without V regions and gp41 deletions. Among them, the 2 or 3 mosaic Env sets elicited the optimal CD4 and CD8 responses. These responses were most evident in CD8 T cells; the 3 mosaic set elicited responses to an average of 8 peptide pools compared to 2 pools for a set of3 natural Env's. Synthetic mosaic HIV -I antigens can therefore induce T-cell responses with expanded breadth and may facilitate the development of effective T -cell-based HIV -1 vaccines.
Bahromov, Mahbat; Weine, Stevan
This study was a pilot investigation of the feasibility, acceptability, and effects of TRAIN (Transit to Russia AIDS Intervention with Newcomers) a three-session HIV preventive intervention for Tajik male labor migrants performed in transit. Sixty adult Tajik male labor migrants on the 5-day train ride from Dushanbe to Moscow were randomly assigned to either the intervention or a control condition. Each initially completed an in-person survey then another 3 days later (immediately postintervention), and participated in a cell phone survey three months later. All participants came to all intervention sessions, were satisfied with the program, and completed all postassessments. In comparison with the controls, the TRAIN group reported significant increases in condom use with sex workers and non-sex workers, condom knowledge, worry about HIV/AIDS, talking with persons about HIV/AIDS, talking with wife about HIV/AIDS, community activities, and religious activities. HIV/AIDS prevention performed in transit is feasible, accceptable, and potentially efficacious in diminishing HIV risk behaviors in labor migrants. PMID:21696244
Bahromov, Mahbat; Weine, Stevan
This study was a pilot investigation of the feasibility, acceptability, and effects of TRAIN (Transit to Russia AIDS Intervention with Newcomers) a three-session HIV preventive intervention for Tajik male labor migrants performed in transit. Sixty adult Tajik male labor migrants on the 5-day train ride from Dushanbe to Moscow were randomly assigned to either the intervention or a control condition. Each initially completed an in-person survey then another 3 days later (immediately postintervention), and participated in a cell phone survey three months later. All participants came to all intervention sessions, were satisfied with the program, and completed all postassessments. In comparison with the controls, the TRAIN group reported significant increases in condom use with sex workers and non-sex workers, condom knowledge, worry about HIV/AIDS, talking with persons about HIV/AIDS, talking with wife about HIV/AIDS, community activities, and religious activities. HIV/AIDS prevention performed in transit is feasible, accceptable, and potentially efficacious in diminishing HIV risk behaviors in labor migrants.
Lu, Y; Ding, J; Chen, Y H
The failure of some candidate HIV-1 vaccines may result from inducing very weak neutralization activity against representative primary viral isolates. Based on our hypothesis that epitope-vaccine may be a new strategy to induce high levels of neutralizing antibodies against HIV-1, we designed two candidate multi-epitope-vaccines, EP1 [C-G-(ELDKWA-GPGRAFY)2-K] and EP2 (CG-GPGRAFY-G-ELDKWA-G-RILAVERYLKD), containing three neutralizing epitopes (GPGRAFY, ELDKWA and RILAVERYLKD) on HIV-1 envelope protein, and expected them to induce epitope-specific antibodies of predefined epitope-specificity. The two peptides were conjugated to carrier protein bovine serum albumin (BSA) and used for immunization of rabbits. Proteins were purified from the rabbit sera induced by both candidate multi-epitope-vaccines (EP1-BSA and EP2-BSA) through affinity chromatography with epitope-peptide-conjugated sepharose-column, and identified as antibodies in silver-staining and immunoblotting. These antibodies were demonstrated to recognize three neutralizing epitopes on peptides and the recombinant gp41 in ELISA-assay and immunoblotting. These results indicated that both candidate multi-epitope-vaccines could induce high levels of antibodies of predefined epitope-specificity which recognized a few of neutralizing epitopes on peptides and protein, providing experimental evidence for the new strategy to develop an effective neutralizing-antibody-based multi-epitope-vaccine against HIV-1.
Thanks to very effective interventions vertical transmission of HIV has been reduced from over 20% ten years ago to less than 2% today in industrialised countries. This progress has been achieved by combined application of different strategies including antiretroviral treatment of pregnant women, elective caesarian section (prior to labour and rupture of membranes) and refraining from breastfeeding. Fortunately, the Swiss Mother & Child HIV Cohort Study (MoCHiV) has been able to support this evolution with several important contributions. Nevertheless the most important challenge in the prevention of vertical HIV transmission remains to be resolved in this decade. This impressive reduction in vertical transmission achieved in the industrialised world and delineated in this article still needs to be carried forward to those countries in the third world where HIV prevalence is much higher and interventions therefore much more needed.
Kim, Eun; Erdos, Geza; Huang, Shaohua; Kenniston, Thomas; Falo, Louis D; Gambotto, Andrea
Since it emerged in Brazil in May 2015, the mosquito-borne Zika virus (ZIKV) has raised global concern due to its association with a significant rise in the number of infants born with microcephaly and neurological disorders such as Guillain-Barré syndrome. We developed prototype subunit and adenoviral-based Zika vaccines encoding the extracellular portion of the ZIKV envelope gene (E) fused to the T4 fibritin foldon trimerization domain (Efl). The subunit vaccine was delivered intradermally through carboxymethyl cellulose microneedle array (MNA). The immunogenicity of these two vaccines, named Ad5.ZIKV-Efl and ZIKV-rEfl, was tested in C57BL/6 mice. Prime/boost immunization regimen was associated with induction of a ZIKV-specific antibody response, which provided neutralizing immunity. Moreover, protection was evaluated in seven-day-old pups after virulent ZIKV intraperitoneal challenge. Pups born to mice immunized with Ad5.ZIKV-Efl were all protected against lethal challenge infection without weight loss or neurological signs, while pups born to dams immunized with MNA-ZIKV-rEfl were partially protected (50%). No protection was seen in pups born to phosphate buffered saline-immunized mice. This study illustrates the preliminary efficacy of the E ZIKV antigen vaccination in controlling ZIKV infectivity, providing a promising candidate vaccine and antigen format for the prevention of Zika virus disease.
Gil, Cristina; Climent, Núria; García, Felipe; Hurtado, Carmen; Nieto-Márquez, Sara; León, Agathe; García, M Teresa; Rovira, Cristina; Miralles, Laia; Dalmau, Judith; Pumarola, Tomás; Almela, Manel; Martinez-Picado, Javier; Lifson, Jeffrey D; Zamora, Laura; Miró, José M; Brander, Christian; Clotet, Bonaventura; Gallart, Teresa; Gatell, José M
This study provides a detailed description and characterization of the preparation of individualized lots of autologous heat inactivated HIV-1 virions used as immunogen in a clinical trial designed to test an autologous dendritic-cell-based therapeutic HIV-1 vaccine (Clinical Trial DCV-2, NCT00402142). For each participant, ex vivo isolation and expansion of primary virus were performed by co-culturing CD4-enriched PBMCs from the HIV-1-infected patient with PBMC from HIV-seronegative unrelated healthy volunteer donors. The viral supernatants were heat-inactivated and concentrated to obtain 1 mL of autologous immunogen, which was used to load autologous dendritic cells of each patient. High sequence homology was found between the inactivated virus immunogen and the HIV-1 circulating in plasma at the time of HIV-1 isolation. Immunogens contained up to 10⁹ HIV-1 RNA copies/mL showed considerably reduced infectivity after heat inactivation (median of 5.6 log₁₀), and were free of specified adventitious agents. The production of individualized lots of immunogen based on autologous inactivated HIV-1 virus fulfilling clinical-grade good manufacturing practice proved to be feasible, consistent with predetermined specifications, and safe for use in a clinical trial designed to test autologous dendritic cell-based therapeutic HIV-1 vaccine.
Waldura, Jess Fogler
Among the most frequently asked questions by callers to the National Perinatal HIV Hotline are those on the use of hormonal contraception in women receiving antiretroviral therapy. Estradiol levels are reduced by ritonavir-boosted protease inhibitors (PIs), nelfinavir, and nevirapine and increased by non-ritonavir-boosted PIs (except nelfinavir), efavirenz, and etravirine. Oral contraceptives do not affect antiretroviral drug levels, and several options are available for hormonal contraception that can compensate for or avoid the effects of antiretroviral drugs on estrogen levels. Other common questions on the hotline involve interpretation and management issues that arise from indeterminate Western blot test results early and late in pregnancy and from positive rapid test results during labor. Many questions focus on appropriate selection of antiretroviral drugs in pregnancy and the need to change regimens to reduce risk of birth defects in the child. This articlesummarizes a presentation by Jess Fogler Waldura, MD, at the 13th Annual Clinical Conference for the Ryan White HIV/AIDS Program held in August 2010 in Washington, DC.
Enjuanes, Luis; DeDiego, Marta L.; Álvarez, Enrique; Deming, Damon; Sheahan, Tim; Baric, Ralph
An important effort has been performed after the emergence of severe acute respiratory syndrome (SARS) epidemic in 2003 to diagnose and prevent virus spreading. Several types of vaccines have been developed including inactivated viruses, subunit vaccines, virus-like particles (VLPs), DNA vaccines, heterologous expression systems, and vaccines derived from SARS-CoV genome by reverse genetics. This review describes several aspects essential to develop SARS-CoV vaccines, such as the correlates of protection, virus serotypes, vaccination side effects, and bio-safeguards that can be engineered into recombinant vaccine approaches based on the SARS-CoV genome. The production of effective and safe vaccines to prevent SARS has led to the development of promising vaccine candidates, in contrast to the design of vaccines for other coronaviruses, that in general has been less successful. After preclinical trials in animal models, efficacy and safety evaluation of the most promising vaccine candidates described has to be performed in humans. PMID:17416434
Yates, Nicole L; Liao, Hua-Xin; Fong, Youyi; deCamp, Allan; Vandergrift, Nathan A; Williams, William T; Alam, S Munir; Ferrari, Guido; Yang, Zhi-yong; Seaton, Kelly E; Berman, Phillip W; Alpert, Michael D; Evans, David T; O'Connell, Robert J; Francis, Donald; Sinangil, Faruk; Lee, Carter; Nitayaphan, Sorachai; Rerks-Ngarm, Supachai; Kaewkungwal, Jaranit; Pitisuttithum, Punnee; Tartaglia, James; Pinter, Abraham; Zolla-Pazner, Susan; Gilbert, Peter B; Nabel, Gary J; Michael, Nelson L; Kim, Jerome H; Montefiori, David C; Haynes, Barton F; Tomaras, Georgia D
HIV-1-specific immunoglobulin G (IgG) subclass antibodies bind to distinct cellular Fc receptors. Antibodies of the same epitope specificity but of a different subclass therefore can have different antibody effector functions. The study of IgG subclass profiles between different vaccine regimens used in clinical trials with divergent efficacy outcomes can provide information on the quality of the vaccine-induced B cell response. We show that HIV-1-specific IgG3 distinguished two HIV-1 vaccine efficacy studies (RV144 and VAX003 clinical trials) and correlated with decreased risk of HIV-1 infection in a blinded follow-up case-control study with the RV144 vaccine. HIV-1-specific IgG3 responses were not long-lived, which was consistent with the waning efficacy of the RV144 vaccine. These data suggest that specific vaccine-induced HIV-1 IgG3 should be tested in future studies of immune correlates in HIV-1 vaccine efficacy trials.
Buchbinder, Susan P; Liu, Albert Y
The 2016 Conference on Retroviruses and Opportunistic Infections (CROI) highlighted hot spots in HIV infection. Men who have sex with men (MSM), transgender populations, people who inject drugs, fisherfolk, migrants, adolescents, and older adults are heavily impacted in a number of regions. Stigma contributes to risk behaviors and HIV acquisition across populations. HIV testing is a crucial first step in the HIV care continuum, and several large community-based surveys are underway in Africa to increase HIV testing, linkage to care, and uptake of antiretroviral treatment. Advances in preexposure prophylaxis (PrEP) featured prominently at CROI 2016. Two large efficacy trials of a vaginal ring containing the investigational drug dapivirine demonstrated efficacy and safety in preventing HIV infections in women in Africa. Data on the safety of long-acting injectable PrEP and several investigational PrEP drugs and formulations were also presented. Knowledge and use of PrEP among MSM in the United States appears to be increasing, and high uptake was seen among black MSM when provided as part of a culturally tailored support program. The use of broadly neutralizing antibodies for HIV prevention is a novel and promising approach to be evaluated in efficacy trials.
Azizi, Ali; Ghorbani, Masoud; Soare, Catalina; Mojibian, Majid; Diaz-Mitoma, Francisco
Dual infections with HIV-1 and Hepatitis C virus (HCV) may proceed in concert to cause severe disease. HIV positive individuals that become infected with HCV advance more rapidly to AIDS than those that are infected with HIV-1 alone. In this study, HLA-A2.1 mice were immunized with a combination vaccine including HIV and HCV immunogens (polycistronic DNA + proteins) or vaccine containing either HIV or HCV immunogens. Mice immunized with the combined HIV/HCV regimen had similar antibody titers as the group receiving either the HIV-1 or HCV only regimen. Proliferative immune responses showed that mice receiving the combined HIV/HCV vaccine exhibited a three fold higher stimulation index (SI) to gp120 than mice immunized with the vaccine containing HIV alone. To determine whether our vaccine strategy induced Th1 or Th2 immune responses, IFN-gamma and IL-4/IL-5 were measured. The combined HIV/HCV vaccine induced a higher level of Th1 responses to HIV-1 gag protein compared with the other groups, as measured by IFN-gamma production. Interestingly, detection of IFN-gamma by ELISPOT assay demonstrated that the combined HIV/HCV vaccine group had increased numbers of spot forming cells (SFC) to HIV-gp120 peptides when compared to that of the HIV-1 only vaccine group. The combined HIV/HCV vaccine group also showed an increase in SFC to HCV-core peptides in comparison with the group receiving the HCV only vaccine. Intracellular IFN-gamma staining confirmed the ELISPOT results and demonstrated that the combined HIV/HCV group had significantly higher percentages of HIV and HCV-specific CD8+ T cells in comparison to the groups receiving the HIV or HCV vaccines. These results suggest a new approach to maximize vaccine efficacy against HIV and HCV.
Thompson, Kimberly M; Duintjer Tebbens, Radboud J
Managing the dynamics of vaccine supply and demand represents a significant challenge with very high stakes. Insufficient vaccine supplies can necessitate rationing, lead to preventable adverse health outcomes, delay the achievements of elimination or eradication goals, and/or pose reputation risks for public health authorities and/or manufacturers. This article explores the dynamics of global vaccine supply and demand to consider the opportunities to develop and maintain optimal global vaccine stockpiles for universal vaccines, characterized by large global demand (for which we use measles vaccines as an example), and nonuniversal (including new and niche) vaccines (for which we use oral cholera vaccine as an example). We contrast our approach with other vaccine stockpile optimization frameworks previously developed for the United States pediatric vaccine stockpile to address disruptions in supply and global emergency response vaccine stockpiles to provide on-demand vaccines for use in outbreaks. For measles vaccine, we explore the complexity that arises due to different formulations and presentations of vaccines, consideration of rubella, and the context of regional elimination goals. We conclude that global health policy leaders and stakeholders should procure and maintain appropriate global vaccine rotating stocks for measles and rubella vaccine now to support current regional elimination goals, and should probably also do so for other vaccines to help prevent and control endemic or epidemic diseases. This work suggests the need to better model global vaccine supplies to improve efficiency in the vaccine supply chain, ensure adequate supplies to support elimination and eradication initiatives, and support progress toward the goals of the Global Vaccine Action Plan.
Jones, Tiffany; Mitchell, Anne
Australia has not seen a Human Immunodeficiency Virus (HIV) epidemic among young people. However, early research in the Australian context had indicated that the degree of unprotected sexual activity, partner change, and STI infection in this cohort would fuel a young people's epidemic if HIV ever reached a tipping point in the country. The difficulty of reaching young people outside school for HIV prevention has been no more successfully addressed in Australia than elsewhere. Therefore, the investment of Australian HIV prevention funds for youth has had an emphasis on school-based programs. This emphasis on formal schooling has led to a history of engagement with the ad hoc and unreliable nature of sexuality education in Australian schools. It has particularly been the catalyst for a struggle to construct young people as sexually active and as possessing a right to appropriate education, against tides of both secular and religiously-motivated resistance. The eight state and territory education sectors, along with the independent sectors, have had differing and sometimes troubled histories with HIV prevention. This paper discusses the differing HIV education policies and programs that have emerged in Australian schooling historically, and in some cases been abandoned altogether, amid strong public debates. It also considers current approaches, the new national curriculum, and future challenges. Additionally, the particular case of same sex attracted young men, who have a heightened level of vulnerability to HIV, is explored. Australian schools have struggled to address both the imperative for relevant sexuality education for same-sex-attracted young people and the broader issue of combating homophobia, which research has linked directly to this vulnerability.
Pérez-Losada, Marcos; Jobes, David V.; Sinangil, Faruk; Crandall, Keith A.; Posada, David; Berman, Phillip W.
In 2003, a phase III placebo-controlled trial (VAX004) of a candidate HIV-1 vaccine (AIDSVAX B/B) was completed in 5,403 volunteers at high risk for HIV-1 infection from North America and the Netherlands. A total of 368 individuals became infected with HIV-1 during the trial. The envelope glycoprotein gene (gp120) from the HIV-1 subtype B viruses infecting 349 patients was sequenced from clinical samples taken as close as possible to the time of diagnosis, rendering a final data set of 1,047 sequences (1,032 from North America and 15 from the Netherlands). Here, we used these data in combination with other sequences available in public databases to assess HIV-1 variation as a function of vaccination treatment, geographic region, race, risk behavior, and viral load. Viral samples did not show any phylogenetic structure for any of these factors, but individuals with different viral loads showed significant differences (P = 0.009) in genetic diversity. The estimated time of emergence of HIV-1 subtype B was 1966–1970. Despite the fact that the number of AIDS cases has decreased in North America since the early 90s, HIV-1 genetic diversity seems to have remained almost constant over time. This study represents one of the largest molecular epidemiologic surveys of viruses responsible for new HIV-1 infections in North America and could help the selection of epidemiologically representative vaccine antigens to include in the next generation of candidate HIV-1 vaccines. PMID:19864468
Fowler, Mary Glenn; Gable, Alicia R; Lampe, Margaret A; Etima, Monica; Owor, Maxensia
This article reviews the epidemiology of perinatal (HIV)-1 in the United States in the past 2 decades and the international HIV epidemic among pregnant women and their infants. Since the peak of 1700 reported cases of pediatric AIDS in 1992, there has been dramatic progress in decreasing perinatal HIV transmission in the United States with fewer than 50 new cases of AIDS annually (>96% reduction) and fewer than 300 annual perinatal HIV transmissions in 2005. This success has been due to use of combination antiretrovirals given to mothers during pregnancy and labor/delivery, obstetric interventions that reduce the risk of transmission, provision of zidovudine (ZDV) prophylaxis for 6 weeks to HIV-exposed newborns and use of formula. Internationally, the burden of mother-to-child HIV transmission remains heavy with 2.1 million children less than 15 years of age estimated to be living with HIV and 430,000 new HIV infections in infants occurring each year, with most cases occurring in Africa. Current international efforts are directed at scaling up successful prevention of mother-to-child transmission interventions and new research directed at making breastfeeding safer using antiretroviral prophylaxis to either mothers or their infants.
Salleras, Luis; Navas, Encarna; Torner, Nuria; Prat, Andreu A.; Garrido, Patricio; Soldevila, Núria; Domínguez, Angela
The aim of this study was to systematically review published studies that evaluated the efficiency of inactivated influenza vaccination in preventing seasonal influenza in children. The vaccine evaluated was the influenza-inactivated vaccine in 10 studies and the virosomal inactivated vaccine in 3 studies. The results show that yearly vaccination of children with the inactivated influenza vaccine saves money from the societal and family perspectives but not from the public or private provider perspective. When vaccination does not save money, the cost-effectiveness ratios were very acceptable. It can be concluded, that inactivated influenza vaccination of children is a very efficient intervention. PMID:23295894
This paper examines the ways in which HIV prevention is understood including "biomedical", "behavioural", "structural", and "combination" prevention. In it I argue that effective prevention entails developing community capacity and requires that public health addresses people not only as individuals but also as connected members of groups, networks and collectives who interact (talk, negotiate, have sex, use drugs, etc.) together. I also examine the evaluation of prevention programmes or interventions and argue that the distinction between efficacy and effectiveness is often glossed and that, while efficacy can be evaluated by randomized controlled trials, the evaluation of effectiveness requires long-term descriptive strategies and/or modelling. Using examples from a number of countries, including a detailed account of the Australian HIV prevention response, effectiveness is shown to be dependent not only on the efficacy of the prevention technology or tool but also on the responses of people - individuals, communities and governments - to those technologies. Whether a particular HIV prevention technology is adopted and its use sustained depends on a range of social, cultural and political factors. The paper concludes by calling on biomedical and social scientists to work together and describes a "social public health".
Tshikung, Olivier Nawej; Calmy, Alexandra
In 2015, the publication of important studies allowed the development of new guidelines, notably by WHO and the European AIDS ClinicalSociety (EACS), for HIV preventive treatment (pre-exposure prophylaxis), as well as for the start of antiretroviral treatment. The START and TEMPRANO studies have extended the treatment to all HIV-infected patients, irrespective of the level of immunosuppression and therefore the CD4 count. In addition, innovative screening methods, such as self-tests, are now available in all French pharmacies since 15 September 2015. The latest developments in 2015 concerning the prevention, screening, and treatment of HIV are discussed in this article and will certainly have an impact on the care of patients in Switzerland.
Tully, Stephen; Cojocaru, Monica; Bauch, Chris T
There has been growing use of highly active antiretroviral treatment (HAART) for HIV and significant progress in developing prophylactic HIV vaccines. The simplest theories of counterproductive behavioral responses to such interventions tend to focus on single feedback mechanisms: for instance, HAART optimism makes infection less scary and thus promotes risky sexual behavior. Here, we develop an agent based, age-structured model of HIV transmission, risk perception, and partner selection in a core group to explore behavioral responses to interventions. We find that interventions can activate not one, but several feedback mechanisms that could potentially influence decision-making and HIV prevalence. In the model, HAART increases the attractiveness of unprotected sex, but it also increases perceived risk of infection and, on longer timescales, causes demographic impacts that partially counteract HAART optimism. Both HAART and vaccination usually lead to lower rates of unprotected sex on the whole, but intervention effectiveness depends strongly on whether individuals over- or under-estimate intervention coverage. Age-specific effects cause sexual behavior and HIV prevalence to change in opposite ways in old and young age groups. For complex infections like HIV-where interventions influence transmission, demography, sexual behavior and risk perception-we conclude that evaluations of behavioral responses should consider multiple feedback mechanisms.
The Female Health Co. (FHC), London, United Kingdom, has signed a three-year agreement with the Joint United Nations Program on HIV/AIDS (UNAIDS) to provide a global public sector price for the female condom to 193 affiliated countries. An adjunct education and social marketing program, supported by UNAIDS, will be launched. High rates of acceptance have been shown previously when the female condom has been introduced with an effective educational approach. Negotiations between FHC and UNAIDS began in September 1996; 80 of 193 countries, upon inquiry, have already identified a requirement for over 7 million female condoms in 1997. UNAIDS estimates that nearly 50% of new human immunodeficiency virus (HIV) infections are in women; the female condom is the only woman-controlled product providing protection against sexually transmitted diseases (STDs), including HIV and acquired immunodeficiency syndrome (AIDS). Studies have indicated that the number of unprotected sex acts decreases when the female condom is available. Dr. Peter Piot (UNAIDS) states that the female condom is important in those cultures and situations where women have limited control over sexual decisions. Dr. Mary Ann Leeper (FHC) states that the company is committed to making the female condom available in developing countries.
Every day, more than 1 million people are newly infected with sexually transmitted infections (STIs) that can lead to morbidity, mortality, and an increased risk of human immunodeficiency virus (HIV) acquisition. Existing prevention and management strategies, including behavior change, condom promotion, and therapy have not reduced the global incidence and prevalence, pointing to the need for novel innovative strategies. This review summarizes important issues raised during a satellite session at the first HIV R4P conference, held in Cape Town, on October 31, 2014. We explore key STIs that are challenging public health today; new biomedical prevention approaches including multipurpose prevention technologies (MPTs); and the scientific and regulatory hurdles that must be overcome to make combination prevention tools a reality. PMID:25759332
Tomusange, Khamis; Wijesundara, Danushka; Gummow, Jason; Garrod, Tamsin; Li, Yanrui; Gray, Lachlan; Churchill, Melissa; Grubor-Bauk, Branka; Gowans, Eric J.
DNA vaccines are cost-effective to manufacture on a global scale and Tat-based DNA vaccines have yielded protective outcomes in preclinical and clinical models of human immunodeficiency virus (HIV), highlighting the potential of such vaccines. However, Tat-based DNA vaccines have been poorly immunogenic, and despite the administration of multiple doses and/or the addition of adjuvants, these vaccines are not in general use. In this study, we improved Tat immunogenicity by fusing it with the oligomerisation domain of a chimeric C4-binding protein (C4b-p), termed IMX313, resulting in Tat heptamerisation and linked Tat to the leader sequence of tissue plasminogen activator (TPA) to ensure that the bulk of heptamerised Tat is secreted. Mice vaccinated with secreted Tat fused to IMX313 (pVAX-sTat-IMX313) developed higher titres of Tat-specific serum IgG, mucosal sIgA and cell-mediated immune (CMI) responses, and showed superior control of EcoHIV infection, a surrogate murine HIV challenge model, compared with animals vaccinated with other test vaccines. Given the crucial contribution of Tat to HIV-1 pathogenesis and the precedent of Tat-based DNA vaccines in conferring some level of protection in animal models, we believe that the virologic control demonstrated with this novel multimerised Tat vaccine highlights the promise of this vaccine candidate for humans. PMID:27358023
Office of the Surgeon General (DHHS/PHS), Washington, DC.
This packet of materials is Phase 1 of a toolkit designed to enlighten education leaders about the need for HIV prevention for youth, especially in communities of color. One element of the toolkit is a VHS videotape that features a brief message from former Surgeon General, Dr. David Satcher. The toolkit also includes a copy of a letter sent to…
Kelly, Jeffrey A.; Murphy, Debra A.
Notes that research to date has yielded important findings for primary prevention efforts for Acquired Immune Deficiency Syndrome (AIDS) and has identified psychological dimensions relevant to mental health interventions for persons with human immunodeficiency virus (HIV). Sees pressing need for more systematic intervention outcome research in…
DeMuth, Diane; Symons, Cynthia Wolford
Presents examples of appropriate intervention strategies for professionals working with school-based human immunodeficiency virus (HIV) prevention among adolescents. A multidisciplinary approach is advisable because influencing adolescent sexual behavior is a complex matter. Consistent, continuous messages through multiple channels and by multiple…
Hohman, Melinda; Shillington, Audrey M.; Min, Jong Won; Clapp, John D.; Mueller, Kristin; Hovell, Melbourne
This study compared two groups of adolescents seeking help at HIV prevention drop-in agencies. The first group attended agencies in low-income Hispanic neighborhoods which recruited within the locale. The second group of youth attended agencies that recruited based upon a specific population--they targeted homeless and LGBQ youth. We explored the…
Goggin, K.; Metcalf, K.; Wise, D.; Kennedy, S.; Murray, T.; Burgess, D.; Reese-Smith, J.; Terhune, N.; Broadus, K.; Downes, A.; Buckendahl, H.
This study evaluates the first year of a novel HIV and substance use prevention program for inner city youth (Offering New Youth eXperiences--ONYX). Baseline and follow-up measures of knowledge, attitudes, and risk behaviors were administered seven months apart to 441 youth participating in the ONYX program. Youth (n=71) who provided data at both…
Fisher, Gloria; And Others
This study was undertaken to evaluate Human Immunodeficiency Virus (HIV) prevention and comprehensive health activities in public secondary schools in Mississippi. The Comprehensive School Health Curriculum (CSHC), for implementation in junior, middle, and senior high schools, was designed to promote improved knowledge and behaviors related to the…
Hennessy, Michael; Mercier, Michele M.; Williams, Samantha P.; Arno, Janet N.
Conducted a formative research study designed to elicit preferences for sexually transmitted disease (STD)/HIV prevention programs from clients at a midwestern STD clinic. Responses of 126 participants show preferences for mixed group or individual meetings with counselors, with extensive intervention less favored than single sessions. Discusses…
Rovniak, Liza S.; Hovell, Melbourne F.; Hofstetter, C. Richard; Blumberg, Elaine J.; Sipan, Carol L.; Batista, Marcia F.; Martinez-Donate, Ana P.; Mulvihill, Mary M.; Ayala, Guadalupe X.
Purpose To explore the feasibility of engaging community businesses in HIV prevention. Design Randomly selected business owners/managers were asked to display discreetly wrapped condoms and brochures provided free-of-charge for 3 months. Assessments were conducted at baseline, mid-, and post-program. Customer feedback was obtained through an online survey. Setting San Diego, California neighborhood with a high rate of AIDS. Subjects Fifty-one business owners/managers representing 10 retail categories, and 52 customers. Measures Participation rates, descriptive characteristics, number of condoms and brochures distributed, customer feedback, business owners'/managers' program satisfaction and willingness to provide future support for HIV prevention. Analysis Kruskal-Wallis, Mann-Whitney U, Fisher's exact, and McNemar's tests were used to analyze data. Results The 20 business owners/managers (39%) who agreed to distribute condoms and brochures reported fewer years in business and more employees than those who agreed only to distribute brochures (20%) or refused to participate (41%), p <.05. Bars were the easiest of ten retail categories to recruit. Businesses with more employees and customers distributed more condoms and brochures, p < .05. More than 90% of customers supported distributing condoms and brochures in businesses and 96% of business owners/managers described their program experience as “positive.” Conclusion Businesses are willing to distribute condoms and brochures to prevent HIV. Policies to increase business participation in HIV prevention should be developed and tested. PMID:20465150
Chakrapani, Venkatesan; Newman, Peter A.; Singhal, Neeti; Jerajani, Jhalak; Shunmugam, Murali
Background Recruitment of low- and middle-income country volunteers from most-at-risk populations in HIV vaccine trials is essential to vaccine development. In India, men who have sex with men (MSM) are at disproportionately high risk for HIV infection and an important population for trial recruitment. Investigations of willingness to participate (WTP) in HIV vaccine trials have focused predominantly on individual-level determinants. We explored multi-level factors associated with WTP among MSM in India. Methods We conducted 12 focus groups (n = 68) with low socioeconomic MSM in Chennai and Mumbai, and 14 key informant interviews with MSM community leaders and service providers. Focus groups/interviews were recorded, transcribed and translated into English. Two bilingual investigators conducted thematic analysis using line-by-line coding and a constant comparative method, with member-checking by community representatives. Results Factors associated with WTP were evidenced across the social ecology of MSM–social-structural: poverty, HIV-, sexual- and gender non-conformity stigma, institutionalized discrimination and government sponsorship of trials; community-level: endorsement by MSM community leaders and organizations, and fear of within-group discrimination; interpersonal: anticipated family discord, partner rejection, having financially-dependent family members and disclosure of same-sex sexuality; and individual-level: HIV vaccine trial knowledge and misconceptions, safety concerns, altruism and preventive misconception. Conclusion Pervasive familial, community and social-structural factors characteristic of the Indian sociocultural context may complicate individual-focused approaches to WTP and thereby constrain the effectiveness of interventions to support recruitment and retention in HIV vaccine trials. Interventions to reduce stigma and discrimination against MSM and people living with HIV, capacity-building of MSM community organizations and
D'Argenio, David A; Wilson, Christopher B
Vaccination stands as one of the most successful public health measures of the last century. New approaches will be needed, however, to develop highly effective vaccines to prevent tuberculosis, HIV-AIDS, and malaria and to eradicate polio. Current advances in immunology and technology have set the stage for rational vaccine design to begin a "Decade of Vaccines."
Sarkar, Anita; Liang, Chi-Hui; Scherer, Erin A.; Henry Dunand, Carole J.; Adachi, Yumiko; Diwanji, Devan; Jones, Meaghan; Kalyuzhniy, Oleksandr; Kubitz, Michael; Spencer, Skye; Pauthner, Matthias; Saye-Francisco, Karen L.; Sesterhenn, Fabian; Wilson, Patrick C.; Galloway, Denise M.; Stanfield, Robyn L.; Wilson, Ian A.; Burton, Dennis R.; Schief, William R.
An optimal HIV vaccine should induce broadly neutralizing antibodies (bnAbs) that neutralize diverse viral strains and subtypes. However, potent bnAbs develop in only a small fraction of HIV-infected individuals, all contain rare features such as extensive mutation, insertions, deletions, and/or long complementarity-determining regions, and some are polyreactive, casting doubt on whether bnAbs to HIV can be reliably induced by vaccination. We engineered two potent VRC01-class bnAbs that minimized rare features. According to a quantitative features frequency analysis, the set of features for one of these minimally mutated bnAbs compared favorably with all 68 HIV bnAbs analyzed and was similar to antibodies elicited by common vaccines. This same minimally mutated bnAb lacked polyreactivity in four different assays. We then divided the minimal mutations into spatial clusters and dissected the epitope components interacting with those clusters, by mutational and crystallographic analyses coupled with neutralization assays. Finally, by synthesizing available data, we developed a working-concept boosting strategy to select the mutation clusters in a logical order following a germline-targeting prime. We have thus developed potent HIV bnAbs that may be more tractable vaccine goals compared to existing bnAbs, and we have proposed a strategy to elicit them. This reductionist approach to vaccine design, guided by antibody and antigen structure, could be applied to design candidate vaccines for other HIV bnAbs or protective Abs against other pathogens. PMID:27560183
Moussa, Maha; Arrode-Brusés, Géraldine; Manoylov, Iliyan; Malogolovkin, Alexander; Mompelat, Dimitri; Ishimwe, Honorine; Smaoune, Amel; Ouzrout, Bilel; Gagnon, Jean; Chebloune, Yahia
Novel HIV vaccine vectors and strategies are needed to control HIV/AIDS epidemic in humans and eradicate the infection. DNA vaccines alone failed to induce immune responses robust enough to control HIV-1. Development of lentivirus-based DNA vaccines deficient for integration and with a limited replication capacity is an innovative and promising approach. This type of vaccine mimics the early stages of virus infection/replication like the live-attenuated viruses but lacks the inconvenient integration and persistence associated with disease. We developed a novel lentivector DNA vaccine "CAL-SHIV-IN(-)" that undergoes a single round of replication in the absence of integration resulting in augmented expression of vaccine antigens in vivo. Vaccine gene expression is under control of the LTRs of a naturally attenuated lentivirus, Caprine arthritis encephalitis virus (CAEV) the natural goat lentivirus. The safety of this vaccine prototype was increased by the removal of the integrase coding sequences from the pol gene. We examined the functional properties of this lentivector DNA in cell culture and the immunogenicity in mouse models. Viral proteins were expressed in transfected cells, assembled into viral particles that were able to transduce once target permissive cells. Unlike the parental replication-competent SHIV-KU2 that was detected in DNA samples from any of the serial passage infected cells, CAL-SHIV-IN(-) DNA was detected only in target cells of the first round of infection, hence demonstrating the single cycle replication of the vaccine. A single dose DNA immunization of humanized NOD/SCID/β2 mice showed a substantial increase of IFN-γ-ELISPOT in splenocytes compared to the former replication and integration defective Δ4SHIV-KU2 DNA vaccine.
Ye, Ling; Wen, Zhiyuan; Dong, Ke; Wang, Xi; Bu, Zhigao; Zhang, Huizhong; Compans, Richard W; Yang, Chinglai
Several conserved neutralizing epitopes have been identified in the HIV Env protein and among these, the MPER of gp41 has received great attention and is widely recognized as a promising target. However, little success has been achieved in eliciting MPER-specific HIV neutralizing antibodies by a number of different vaccine strategies. We investigated the ability of HA/gp41 chimeric protein-based vaccines, which were designed to enhance the exposure of the MPER in its native conformation, to induce MPER-specific HIV neutralizing antibodies. In characterization of the HA/gp41 chimeric protein, we found that by mutating an unpaired Cys residue (Cys-14) in its HA1 subunit to a Ser residue, the modified chimeric protein HA-C14S/gp41 showed increased reactivity to a conformation-sensitive monoclonal antibody against HA and formed more stable trimers in VLPs. On the other hand, HA-C14S/gp41 and HA/gp41 chimeric proteins expressed on the cell surfaces exhibited similar reactivity to monoclonal antibodies 2F5 and 4E10. Immunization of guinea pigs using the HA-C14S/gp41 DNA or VLP vaccines induced antibodies against the HIV gp41 as well as to a peptide corresponding to a segment of MPER at higher levels than immunization by standard HIV VLPs. Further, sera from vaccinated guinea pigs were found to exhibit HIV neutralizing activities. Moreover, sera from guinea pigs vaccinated by HA-C14S/gp41 DNA and VLP vaccines but not the standard HIV VLPs, were found to neutralize HIV pseudovirions containing a SIV-4E10 chimeric Env protein. The virus neutralization could be blocked by a MPER-specific peptide, thus demonstrating induction of MPER-specific HIV neutralizing antibodies by this novel vaccine strategy. These results show that induction of MPER-specific HIV neutralizing antibodies can be achieved through a rationally designed vaccine strategy.
Faust, Helena; Toft, Lars; Sehr, Peter; Müller, Martin; Bonde, Jesper; Forslund, Ola; Østergaard, Lars; Tolstrup, Martin; Dillner, Joakim
Ninety-one HIV-infected individuals (61 men and 30 women) were randomized to vaccination either with quadrivalent (Gardasil™) or bivalent (Cervarix™) HPV vaccine. Neutralizing and specific HPV-binding serum antibodies were measured at baseline and 12 months after the first vaccine dose. Presence of neutralizing and binding antibodies had good agreement (average Kappa for HPV types 6, 11, 16, 18, 31, 33 and 45 was 0.65). At baseline, 88% of subjects had antibodies against at least one genital HPV. Following vaccination with Cervarix™, all subjects became seropositive for HPV16 and 18. After Gardasil™ vaccination, 96% of subjects seroconverted for HPV16 and 73% for HPV18. Levels of HPV16-specific antibodies were <1 international unit (IU) in 87% of study subjects before vaccination but >10IU in 85% of study subjects after vaccination. Antibodies against non-vaccine HPV types appeared after Gardasil™ vaccination for >50% of vaccinated females for HPV 31, 35 and 73 and for >50% of Cervarix™-vaccinated females for HPV 31, 33, 35, 45, 56 and 58. Cross-reactivity with non-genital HPV types was also detected. In conclusion, HIV-infected subjects responded to HPV vaccination with induction of neutralizing antibodies against both vaccine and non-vaccine types.
Brezar, Vedran; Godot, Véronique; Cheng, Liang; Su, Lishan; Lévy, Yves; Seddiki, Nabila
Efficient vaccines are characterized by the establishment of long-lived memory T cells, including T-helper (effectors and follicular) and T-regulatory cells (Tregs). While the former induces cytotoxic or antibody responses, the latter regulates immune responses by maintaining homeostasis. The role of Tregs in inflammatory conditions is ambiguous and their systematic monitoring in vaccination along with effector T-cells is not instinctive. Recent studies from the cancer field clearly showed that Tregs suppress vaccine-induced immune responses and correlate with poor clinical benefit. In HIV infection, Tregs are needed during acute infection to preserve tissue integrity from an overwhelmed activation, but are not beneficial in chronic infection as they suppress anti-HIV responses. Current assays used to evaluate vaccine-induced specific responses are limited as they do not take into account antigen-specific Tregs. However, new assays, such as the OX40 assay, which allow for the simultaneous detection of a full range of Th-responses including antigen-specific Tregs responses, can overcome these issues. In this review article we will revise the role of Tregs in vaccination and review the recent work performed in the field, including the available tools to monitor them, from novel assays to humanized mouse models.
Vernooij, Eva; Mehlo, Mandhla; Hardon, Anita; Reis, Ria
This article explores how notions of the individual and population are evoked in two ongoing HIV treatment as prevention (TasP) implementation studies in Swaziland. By contrasting policy discourses with lived kinship experiences of people living with HIV, we seek to understand how TasP unfolds in the Swazi context. Data collection consisted of eight focus group discussions with people living with HIV who were members of support groups to examine their perspectives about TasP. In addition, 18 key informant interviews were conducted with study team members, national-level policy-makers and NGO representatives involved in the design of health communication messages about TasP in Swaziland. Thematic analysis was used to identify recurrent themes in transcripts and field notes. Policy-makers and people living with HIV actively resisted framing HIV treatment as a prevention technology but promoted it as (earlier) access to treatment for all. TasP was not conceptualised in terms of individual or societal benefits, which are characteristic of international public health debates; rather its locally situated meanings were embedded in kinship experiences, concerns about taking responsibility for one's own health and others, local biomedical knowledge about drug resistance, and secrecy. The findings from this study suggest that more attention is needed to understand how the global discourse of TasP becomes shaped in practice in different cultural contexts.
HIV infection is the greatest health crisis in human history. It continues to spread unchecked among the poor in the developing world because we have failed to design simple preventative methods that are available and affordable to those living on under $2 a day. Five new methods are discussed. (i) A natural microbicide. Intravaginal lime or lemon juice has been used for centuries as a traditional contraceptive. The juice can also kill HIV in the laboratory, but clinical trials are needed to see if vaginal application is acceptable, safe and effective. (ii) Intravaginal oestrogen. Monkeys can be protected from Simian immunodeficiency virus (SIV) infection by keratinizing the vagina with topical oestrogen. If women take the oral contraceptive pill vaginally it retains its contraceptive efficacy, and the oestrogen it contains should thicken the vagina and protect against HIV infection. Clinical trials are needed. (iii) Male circumcision. Removal of the inner foreskin removes the main site of HIV entry into the penis, resulting in a sevenfold reduction in susceptibility to infection. The practice needs to be promoted. (iv) Post-coital penile hygiene. Wiping the penis immediately after intercourse with lime or lemon juice or vinegar should kill the virus before it has had a chance to infect. A clinical trial of efficacy is needed. (v) PhotoVoice. Asking schoolchildren in developing countries to photograph their impressions of HIV/AIDS is a powerful way of getting them to discuss the subject openly, and develop their own preventative strategies. PMID:16627296
Grassly, N. C.; Garnett, G. P.; Schwartländer, B.; Gregson, S.; Anderson, R. M.
Planning an intervention to prevent infections with the human immunodeficiency virus (HIV) should be guided by local epidemiological and socioeconomic conditions. The socioeconomic setting and existing public service capacity determine whether an intervention can have a significant outcome in terms of a reduction in a defined risk. The epidemiological context determines whether such risk reduction translates into a measurable impact on HIV incidence. Measurement of variables describing the epidemiological context can be used to determine the local suitability of interventions, thereby guiding planners and policy-makers in their choice of intervention. Such measurements also permit the retrospective analysis of the impact of interventions where HIV incidence was not recorded. The epidemiological context is defined for four different categories of intervention, shown to be effective in lower-income countries by randomized controlled trials. Appropriate indicators for the epidemiological context and methodological guidelines for their measurement are proposed. Their use in the transfer of a successful intervention from one context to another and in scaling up the effort to control HIV infection is explored. These indicators should provide a useful resource for those involved in planning HIV prevention interventions. PMID:11799444
Short, R V
HIV infection is the greatest health crisis in human history. It continues to spread unchecked among the poor in the developing world because we have failed to design simple preventative methods that are available and affordable to those living on under Dollars 2 a day. Five new methods are discussed. (i) A natural microbicide. Intravaginal lime or lemon juice has been used for centuries as a traditional contraceptive. The juice can also kill HIV in the laboratory, but clinical trials are needed to see if vaginal application is acceptable, safe and effective. (ii) Intravaginal oestrogen. Monkeys can be protected from Simian immunodeficiency virus (SIV) infection by keratinizing the vagina with topical oestrogen. If women take the oral contraceptive pill vaginally it retains its contraceptive efficacy, and the oestrogen it contains should thicken the vagina and protect against HIV infection. Clinical trials are needed. (iii) Male circumcision. Removal of the inner foreskin removes the main site of HIV entry into the penis, resulting in a sevenfold reduction in susceptibility to infection. The practice needs to be promoted. (iv) Post-coital penile hygiene. Wiping the penis immediately after intercourse with lime or lemon juice or vinegar should kill the virus before it has had a chance to infect. A clinical trial of efficacy is needed. (v) PhotoVoice. Asking schoolchildren in developing countries to photograph their impressions of HIV/AIDS is a powerful way of getting them to discuss the subject openly, and develop their own preventative strategies.
Guetard, Denise; Greco, Raffaella; Cervantes Gonzalez, Minerva; Celli, Susanna; Kostrzak, Anna; Langlade-Demoyen, Pierre; Sala, Francesco; Wain-Hobson, Simon; Sala, Monica
Transgenic tobacco plants expressing a HIV-1 polyepitope associated with hepatitis B (HBV) virus-like particles (VLPs) were previously described. It is demonstrated here that oral administration of these transgenic plants to humanized HSB mice to boost DNA-priming can elicit anti-HIV-1 specific CD8+ T cell activation detectable in mesenteric lymph nodes. Nevertheless, a significant regulatory T cell activation was induced in vivo by the vaccination protocols. The balance between tolerance and immunogenicity remains the main concern in the proof of concept of plant-based vaccine.
Poles, Jordan; Alvarez, Yelina
Abstract CD4+ T cells in the mucosa of the gastrointestinal (GI) tract are preferentially targeted and depleted by HIV. As such, the induction of an effective anti-HIV immune response in the mucosa of the GI tract—through vaccination—could protect this vulnerable population of cells. Mucosal vaccination provides a promising means of inducing robust humoral and cellular responses in the GI tract. Here we review data from the literature about the effectiveness of various mucosal vaccination routes—oral (intraintestinal/tonsilar/sublingual), intranasal, and intrarectal—with regard to the induction of immune responses mediated by cytotoxic T cells and antibodies in the GI mucosa, as well as protective efficacy in challenge models. We present data from the literature indicating that mucosal routes have the potential to effectively elicit GI mucosal immunity and protect against challenge. Given their capacity for the induction of anti-HIV immune responses in the GI mucosa, we propose that mucosal routes, including the nonconventional sublingual, tonsilar, and intrarectal routes, be considered for the delivery of the next generation HIV vaccines. However, further studies are necessary to determine the ideal vectors and vaccination regimens for these routes of immunization and to validate their efficacy in controlling HIV infection. PMID:25354023
Rolland, Morgane; Manocheewa, Siriphan; Swain, J Victor; Lanxon-Cookson, Erinn C; Kim, Moon; Westfall, Dylan H; Larsen, Brendan B; Gilbert, Peter B; Mullins, James I
To overcome the problem of HIV-1 variability, candidate vaccine antigens have been designed to be composed of conserved elements of the HIV-1 proteome. Such candidate vaccines could be improved with a better understanding of both HIV-1 evolutionary constraints and the fitness cost of specific mutations. We evaluated the in vitro fitness cost of 23 mutations engineered in the HIV-1 subtype B Gag-p24 Center-of-Tree (COT) protein through fitness competition assays. While some mutations at conserved sites exacted a high fitness cost, as expected under the assumption that the most conserved residue confers the highest fitness, there was no overall strong relationship between sequence conservation and replicative capacity. By comparing sites that have evolved since the beginning of the epidemic to those that have remain unchanged, we found that sites that have evolved over time were more likely to correspond to HLA-associated sites and that their mutation had limited fitness costs. Our data showed no transcendent link between high conservation and high fitness cost, indicating that merely focusing on conserved segments of HIV-1 would not be sufficient for a successful vaccine strategy. Nonetheless, a subset of sites exacted a high fitness cost upon mutation--these sites have been under selective pressure to change since the beginning of the epidemic but have proved virtually nonmutable and could constitute preferred targets for vaccine design.
Lau, Chuen-Yen; Swann, Edith M; Singh, Sagri; Kafaar, Zuhayr; Meissner, Helen I; Stansbury, James P
HIV vaccine clinical research occurs within a context where biomedical science and social issues are interlinked. Previous HIV vaccine research has considered behavioral and social issues, but often treated them as independent of clinical research processes. Systematic attention to the intersection of behavioral and social issues within a defined clinical research framework is needed to address gaps, such as those related to participation in trials, completion of trials, and the overall research experience. Rigorous attention to these issues at project inception can inform trial design and conduct by matching research approaches to the context in which trials are to be conducted. Conducting behavioral and social sciences research concurrent with vaccine clinical research is important because it can help identify potential barriers to trial implementation, as well as ultimate acceptance and dissemination of trial results. We therefore propose a conceptual framework for behavioral and social science in HIV vaccine clinical research and use examples from the behavioral and social science literature to demonstrate how the model can facilitate identification of significant areas meriting additional exploration. Standardized use of the conceptual framework could improve HIV vaccine clinical research efficiency and relevance.
Europrise is a Network of Excellence supported by the European Commission within the 6th Framework programme from 2007 to 2012. The Network has involved over 50 institutions from 13 European countries together with 3 industrial partners and 6 African countries. The Network encompasses an integrated program of research, training, dissemination and advocacy within the field of HIV vaccines and microbicides. A central and timely theme of the Network is the development of the unique concept of co-usage of vaccines and microbicides. Training of PhD students has been a major task, and some of these post-graduate students have here summarized novel ideas emanating from presentations at the last annual Europrise meeting in Prague. The latest data and ideas concerning HIV vaccine and microbicide studies are included in this review; these studies are so recent that the majority have yet to be published. Data were presented and discussed concerning novel immunisation strategies; microbicides and PrEP (alone and in combination with vaccines); mucosal transmission of HIV/SIV; mucosal vaccination; novel adjuvants; neutralizing antibodies; innate immune responses; HIV/SIV pathogenesis and disease progression; new methods and reagents. These – necessarily overlapping topics - are comprehensively summarised by the Europrise students in the context of other recent exciting data. PMID:22784600
Shollenberger, Lisa M; Bui, Cac T; Paterson, Yvonne; Nyhoff, Lindsay; Harn, Donald A
In areas co-endemic for helminth parasites and HIV/AIDS, infants are often administered vaccines prior to infection with immune modulatory helminth parasites. Systemic Th2 biasing and immune suppression caused by helminth infection reduces cell-mediated responses to vaccines such as tetanus toxoid and BCG. Therefore, we asked if infection with helminthes post-vaccination, alters already established vaccine induced immune responses. In our model, mice are vaccinated against HIV-1 Gag using a Listeria vaccine vector (Lm-Gag) in a prime-boost manner, then infected with the human helminth parasite Schistosoma mansoni. This allows us to determine if established vaccine responses are maintained or altered after helminth infection. Our second objective asked if helminth infection post-vaccination alters the recipient's ability to respond to a second boost. Here we compared responses between uninfected mice, schistosome infected mice, and infected mice that were given an anthelminthic, which occurred coincident with the boost or four weeks prior, as well as comparing to un-boosted mice. We report that HIV-1 vaccine-specific responses generated by Listeria vector HIV-1 vaccines are maintained following subsequent chronic schistosome infection, providing further evidence that Listeria vector vaccines induce potent vaccine-specific responses that can withstand helminth infection. We also were able to demonstrate that administration of a second Listeria boost, which markedly enhanced the immune response, was minimally impacted by schistosome infection, or anthelminthic therapy. Surprisingly, we also observed enhanced antibody responses to HIV Gag in vaccinated mice subsequently infected with schistosomes.
Maksud, Ivia; Fernandes, Nilo Martinez; Filgueiras, Sandra Lucia
This article aims to consider some relevant challenges to the provision of "new prevention technologies" in health services in a scenario where the "advances" in the global response to AIDS control are visible. We take as material for analysis the information currently available on the HIV post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP), treatment as prevention (TASP) and over the counter. The methodology consisted of the survey and analysis of the Biblioteca Virtual em Saúde (BVS: MEDLINE, LILACS, WHOLIS, PAHO, SciELO) articles that addressed the issue of HIV prevention and care in the context of so-called new prevention technologies. The results of the studies show that there is assistance on the ground of clinics for the treatment of disease responses, but there are several challenges related to the sphere of prevention. The articles list some challenges regarding to management, organization of services and the attention given by health professionals to users. The current context shows evidence of the effectiveness of antiretroviral therapy in reducing the risk of HIV transmission, but the challenges for the provision of preventive technologies in health services permeate health professionals and users in their individual dimensions and health services in organizational and structural dimension. Interventions should be made available in a context of community mobilization; there should be no pressure on people to make HIV testing, antiretroviral treatment or for prevention. In the management is responsible for the training of health professionals to inform, clarify and make available to users, partners and family information about the new antiretroviral use strategies.
Pitisuttithum, P; Migasena, S; Laothai, A; Suntharasamai, P; Kumpong, C; Vanichseni, S
Out of 91 volunteers enrolled for the HIV vaccine trial, only 33 volunteers were eligible for vaccination. Of 33 volunteers recruited, 59 per cent of them had incomes of more than 5,000 Baht/ month. The median duration of drug addicts was 15 years (range 1-26 years) and 42 per cent never used condoms during sexual intercourse. As far as consent comprehension was concerned, all of them understood.
Cohen, Myron S.; Chen, Ying Q.; McCauley, Marybeth; Gamble, Theresa; Hosseinipour, Mina C.; Kumarasamy, Nagalingeswaran; Hakim, James G.; Kumwenda, Johnstone; Grinsztejn, Beatriz; Pilotto, Jose H.S.; Godbole, Sheela V.; Chariyalertsak, Suwat; Santos, Breno R.; Mayer, Kenneth H.; Hoffman, Irving F.; Eshleman, Susan H.; Piwowar-Manning, Estelle; Cottle, Leslie; Zhang, Xinyi C.; Makhema, Joseph; Mills, Lisa A.; Panchia, Ravindre; Faesen, Sharlaa; Eron, Joseph; Gallant, Joel; Havlir, Diane; Swindells, Susan; Elharrar, Vanessa; Burns, David; Taha, Taha E.; Nielsen-Saines, Karin; Celentano, David D.; Essex, Max; Hudelson, Sarah E.; Redd, Andrew D.; Fleming, Thomas R.
BACKGROUND An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission. METHODS We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1– negative partner in an intention-to-treat analysis. RESULTS Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant. CONCLUSIONS The early initiation of ART led to a sustained
LeBlanc, Tanya Telfair; Reid, Laurie C.
Abstract In the United States, women are a significant proportion of the correctional population. Women also account for an increasing proportion of newly diagnosed human immunodeficiency virus (HIV) cases. When compared with white women, black women have higher incarceration rates and represent more of the newly diagnosed HIV cases. Correctional facilities offer an opportunity to provide women with HIV testing and prevention services so that they will know their status and receive HIV/sexually transmitted disease (STD) risk-reduction counseling and other preventive services. In this report, we describe incarcerated population statistics and HIV surveillance epidemiology for women. We also describe HIV prevention activities undertaken by the Centers for Disease Control and Prevention's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. Additional research, program development, and implementation are needed to improve HIV prevention efforts for high-risk women. PMID:24116966
Holcomb, K; Weinberg, J M
Varicella-zoster virus is the causal agent of varicella and herpes zoster (HZ) in humans. HZ results from reactivation of latent varicella-zoster virus (VZV) within the sensory ganglia. The incidence and severity of HZ increase with advancing age; more than half of all persons in whom HZ develops are older than 60 years. The most frequent debilitating complication is postherpetic neuralgia, a neuropathic pain syndrome that persists or develops after the dermatomal rash has healed, and can be prolonged and disabling. There are many limitations of the current therapies for HZ and postherpetic neuralgia. A live attenuated VZV vaccine has been developed and recently approved by the United States Food and Drug Administration (FDA) and the European Union for the prevention of HZ in individuals 60 years of age and older. In a randomized, double-blind, placebo-controlled trial 38,546 adults of 60 years of age or older, the use of the HZ vaccine reduced the burden of illness due to HZ by 61.1% (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5% (P<0.001), and reduced the incidence of HZ by 51.3% (P<0.001). In this review, the authors will discuss the history of the use of the varicella vaccine in children, and the subsequent development of the new HZ vaccine.
Chandler, Rasheeta; Anstey, Erica H; Ross, Henry; Morrison-Beedy, Dianne
HIV prevention interventions can help college students engage in safe sexual behaviors. We used the Information, Motivation, Behavioral Skills model to frame four focus group discussions with Black women (n = 32) attending a historically Black college/university or a traditional university to understand their HIV prevention needs. Participants wanted clear information about sexually transmitted infections/HIV and access to contraception. Motivators for practicing safe sex were related to cultural and religious expectations, desire to avoid pregnancy, and conscious efforts to defy racial stereotypes. Barriers to practicing safe sex included issues of accountability, stigma associated with accessing HIV testing/prevention services, and media influences. We found general consensus about the need to develop skill-building HIV prevention interventions focused on communication skills, condom negotiation, access to services, and empowerment. We offer insight into culture- and age-appropriate HIV prevention for Black college women to guide the development of future interventions.
Fisher, Celia B
This special issue of the Journal of Empirical Research on Human Research Ethics represents a sampling of projects fostered through the NIDA-funded Fordham University HIV Prevention Research Ethics Institute. The first three articles employ processes of co-learning to give voice to the experiences of individuals recovering from substance abuse and engaged in sex work who have participated in HIV prevention studies in the United States, India, and the Philippines. The fourth article describes a unique community-based approach to the development of research ethics training modules designed to increase participation of American Indian and Alaskan Native (AI/AN) tribal members as partners in research on health disparities. The last two articles focus a critical scholarly lens on two underexamined areas confronting IRB review of HIV research: The emerging and continuously changing ethical challenges of using social media sites for recruitment into HIV prevention research, and the handling of research-related complaints from participants involving perceived research harms or research experiences that do not accord with their initial expectations. Together, the articles in this special issue identify key ethical crossroads and provide suggestions for best practices that respect the values and merit the trust of research participants.
Cluver, Lucie Dale; Orkin, Frederick Mark; Meinck, Franziska; Boyes, Mark Edward; Sherr, Lorraine
Introduction Social protection is high on the HIV-prevention agenda for youth in sub-Saharan Africa. However, questions remain: How do unconditional cash transfers work? What is the effect of augmenting cash provision with social care? And can “cash plus care” social protection reduce risks for adolescents most vulnerable to infection? This study tackles these questions by first identifying mediated pathways to adolescent HIV risks and then examining potential main and moderating effects of social protection in South Africa. Methods This study was a prospective observational study of 3515 10-to-17-year-olds (56.7% female; 96.8% one-year retention). Within randomly selected census areas in four rural and urban districts in two South African provinces, all homes with a resident adolescent were sampled between 2009/2010 and 2011/2012. Measures included 1) potential structural drivers of HIV infection such as poverty and community violence; 2) HIV risk behaviours; 3) hypothesized psychosocial mediating factors; and 4) types of social protection involving cash and care. Using gender-disaggregated analyses, longitudinal mediation models were tested for potential main and moderating effects of social protection. Results Structural drivers were associated with increased onset of adolescent HIV risk behaviour (p<0.001, B=0.06, SE=0.01), fully mediated by increased psychosocial problems. Both cash and care aspects of social protection were associated with reductions in HIV risk behaviour and psychosocial deprivations. In addition, cash social protection moderated risk pathways: for adolescent girls and boys experiencing more acute structural deprivation, social protection had the greatest associations with HIV risk prevention (e.g. moderation effects for girls: B=−0.08, p<0.002 between structural deprivation and psychosocial problems, and B=−0.07, p<0.001 between psychosocial problems and HIV risk behaviour). Conclusions Adolescents with the greatest structural
Gamble, Lena J; Matthews, Qiana L
Since its discovery and characterization in the early 1980s as a virus that attacks the immune system, there has been some success for the treatment of human immunodeficiency virus-1 (HIV-1) infection. However, due to the overwhelming public health impact of this virus, a vaccine is needed urgently. Despite the tireless efforts of scientist and clinicians, there is still no safe and effective vaccine that provides sterilizing immunity. A vaccine that provides sterilizing immunity against HIV infection remains elusive in part due to the following reasons: 1) degree of diversity of the virus, 2) ability of the virus to evade the hosts’ immunity, and 3) lack of appropriate animal models in which to test vaccine candidates. There have been several attempts to stimulate the immune system to provide protection against HIV-infection. Here, we will discuss attempts that have been made to induce sterilizing immunity, including traditional vaccination attempts, induction of broadly neutralizing antibody production, DNA vaccines, and use of viral vectors. Some of these attempts show promise pending continued research efforts. PMID:21267356
Ocampo, Thad F; Le, Tuan; Matthews, Peter E; Okulicz, Jason F
Streptococcus pneumoniae infection is a predominant cause of bacterial infection in HIV-infected individuals. However, reported rates of pneumococcal vaccination with 23-valent polysaccharide vaccine (PPV23) are variable. We evaluated uptake of PPV23 in patients diagnosed with HIV between 1996 and 2012 (n = 507) in the United States Air Force, a centralized HIV program with free access to care including vaccines and medications. A total of 411 (81.1%) patients received at least 1 PPV23 dose. The PPV23 vaccination within 1 year of diagnosis was greater for those diagnosed between 2004 and 2012 (n = 184, 86%) compared with 1996 to 2003 (n = 104, 56.5%; P < .001). For those with ≥6 years of follow-up, receipt of a second recommended PPV23 dose was greater for those diagnosed between 1996 and 2003 (n = 52, 57.8%) compared with 2004 to 2012 (n = 9, 28.1%; P = .004). Although first PPV23 vaccination was high in recent years, process improvement efforts are underway to overcome barriers and improve uptake of pneumococcal vaccines in our program.
Ndirangu, James; Bärnighausen, Till; Tanser, Frank; Tint, Khin; Newell, Marie-Louise
Objectives To analyse coverage of childhood vaccinations in a rural South African population and investigate whether maternal HIV status is associated with children’s vaccination status. Methods 2 431 children with complete information, 12–23 months of age at some point during the period January 2005 through December 2006 and resident in the Africa Centre Demographic Surveillance Area at the time of their birth were investigated. We examined the relationship between maternal HIV status and child vaccination status for five vaccinations [Bacillus Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP3), poliomyelitis (polio3), hepatitis B (HepB3), and measles] in multiple logistic regressions, controlling for household wealth, maternal age, maternal education and distances to roads, fixed and mobile clinics. Results Coverage of the five vaccinations ranged from 89.3% (95% CI 81.7–93.9) for BCG to 77.3% (67.1–83.6) for measles. Multivariably, maternal HIV-positive status was significantly associated with lower adjusted odds ratios (AOR) of child vaccination for all vaccines [(AOR) 0.60–0.74, all P≤ 0.036] except measles (0.75, P= 0.073), distance to mobile clinic was negatively associated with vaccination status (all P≤ 0.029), household wealth was positively (all P≤ 0.013) and distance to nearest road negatively (all P≤ 0.004) associated with vaccination status. Conclusion Positive maternal HIV status independently reduces children’s probability to receive child vaccinations, which likely contributes to the morbidity and mortality differential between children of HIV-positive and HIV-negative mothers. As a means of increasing vaccination coverage, policy makers should consider increasing the number of mobile clinics in this and similar communities in rural Africa. PMID:19737375
Ballester-Arnal, R; Gil-Llario, M D; Salmeron-Sánchez, P; Giménez-García, C
The sex industry, where men sell sexual services to other men or women, has grown in recent years. These men who offer sexual services are particularly vulnerable to HIV infection due to such factors as: frequency of risky sexual practices, number of sex partners, drug-taking, prevalence of sexually-transmitted infections (STI) and their specific situation of social exclusion which may hinder access to health services. These multi-faceted realities faced by sex workers explain the burgeoning interest in new avenues of scientific research. There are too few preventive programs however aimed at this population group and the studies that evaluate their effectiveness are fewer still. In this article we survey more recent studies on the difficulties of implementing programs for HIV prevention in male sex workers (MSW), as well as the studies that have gauged the impact of preventive programs in this group.
This paper compares policies on named HIV testing in the context of HIV prevention in Britain, Hungary and Sweden, and considers the extent to which these policies are based on evidence of effectiveness or on other, more contextual, factors. In Britain, testing has not featured significantly as a prevention strategy, and named testing has generally been carried out only with the voluntary, informed consent of individuals. In Hungary, testing is central to HIV prevention, and is required by law of certain groups. HIV testing is carried out mainly on a voluntary basis in Sweden, but, unlike in Britain, it has been actively promoted by public health authorities. The paper contrasts the 'right not to know' one's HIV status which is widely respected in Britain, with the 'responsibility to find out' which is more pervasive in Hungary and Sweden. Although policy makers in all three countries appear convinced that their's is the right approach, there appears to be as yet a dearth of convincing evidence to support their arguments.