Varicella zoster virus vaccines: potential complications and possible improvements.

PubMed

Silver, Benjamin; Zhu, Hua

2014-10-01

Varicella zoster virus (VZV) is the causative agent of varicella (chicken pox) and herpes zoster (shingles). After primary infection, the virus remains latent in sensory ganglia, and reactivates upon weakening of the cellular immune system due to various conditions, erupting from sensory neurons and infecting the corresponding skin tissue. The current varicella vaccine (v-Oka) is highly attenuated in the skin, yet retains its neurovirulence and may reactivate and damage sensory neurons. The reactivation is sometimes associated with postherpetic neuralgia (PHN), a severe pain along the affected sensory nerves that can linger for years, even after the herpetic rash resolves. In addition to the older population that develops a secondary infection resulting in herpes zoster, childhood breakthrough herpes zoster affects a small population of vaccinated children. There is a great need for a neuro-attenuated vaccine that would prevent not only the varicella manifestation, but, more importantly, any establishment of latency, and therefore herpes zoster. The development of a genetically-defined live-attenuated VZV vaccine that prevents neuronal and latent infection, in addition to primary varicella, is imperative for eventual eradication of VZV, and, if fully understood, has vast implications for many related herpesviruses and other viruses with similar pathogenic mechanisms.

Safety, humoral and cell-mediated immune responses to herpes zoster vaccine in subjects with diabetes mellitus.

PubMed

Hata, Atsuko; Inoue, Fukue; Yamasaki, Midori; Fujikawa, Jun; Kawasaki, Yukiko; Hamamoto, Yoshiyuki; Honjo, Sachiko; Moriishi, Eiko; Mori, Yasuko; Koshiyama, Hiroyuki

2013-09-01

To evaluate varicella zoster virus-specific cell-mediated immunity and humoral immunogenicity against the herpes zoster vaccine, which is licensed as the Live Varicella Vaccine (Oka Strain) in Japan, in elderly people with or without diabetes mellitus. A pilot study was conducted between May 2010 and November 2010 at Kitano Hospital, a general hospital in the city of Osaka in Japan. A varicella skin test, interferon-gamma enzyme-linked immunospot assay and immunoadherence hemagglutination tests were performed 0, 3, and 6 months after vaccination. Vaccine safety was also assessed using questionnaires for 42 days and development of zoster during the one-year observational period. We enrolled 10 healthy volunteers and 10 patients with diabetes mellitus aged 60-70 years. The live herpes zoster vaccine boosted virus-specific, cell-mediated and humoral immunity between elderly people, with or without diabetes. Moreover, no systemic adverse reaction was found. None of the study participants developed herpes zoster. The live herpes zoster vaccine was used safely. It effectively enhanced specific immunity to varicella zoster virus in older people with or without diabetes mellitus. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Comparing health outcomes and costs of general vaccination with pneumococcal conjugate vaccines in Sweden: a Markov model.

PubMed

By, Asa; Sobocki, Patrik; Forsgren, Arne; Silfverdal, Sven-Arne

2012-01-01

Two new pneumococcal conjugate vaccines were licensed to immunize infants and young children against pneumococcal disease. The objective of this study was to estimate the expected health benefits, costs, and incremental cost-effectiveness of routine vaccination with the 10-valent pneumococcal nontypeable hemophilus influenza protein-D conjugate vaccine (PHiD-CV) compared with the 13-valent pneumococcal conjugate vaccine (PCV13) in Sweden. A Markov cohort model was used to estimate the effect of vaccination at vaccine steady state, taking a societal perspective and using a 2+1 vaccination schedule. Price parity was assumed between the vaccines. Outcomes were measured by reduction in disease burden, costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio. The results predicted that PCV13 would prevent 3 additional cases of invasive pneumococcal disease and 34 additional cases of pneumonia, whereas PHiD-CV would avoid 3 additional cases of mastoiditis, 1010 tube insertions, and 10,420 cases of ambulatory acute otitis media compared with PCV13. By combining morbidity and mortality benefits of all clinical outcomes, PHiD-CV would generate 45.3 additional QALYs compared with PCV13 and generate savings of an estimated 62 million Swedish kronors. The present study predicted lower costs and better health outcome (QALYs) gained by introducing PHiD-CV compared with PCV13 in routine vaccination. Our results indicated that PHiD-CV is cost-effective compared with PCV13 in Sweden. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Latency of Varicella Zoster Virus in Dorsal Root, Cranial, and Enteric Ganglia in Vaccinated Children

PubMed Central

Gershon, Anne A.; Chen, Jason; Davis, Larry; Krinsky, Clarissa; Cowles, Robert; Reichard, Ross; Gershon, Michael

2012-01-01

Despite vaccination, varicella-zoster virus (VZV) remains an important pathogen. We investigated VZV latency in autopsy specimens from vaccinees, in gastrointestinal tissue removed surgically, and in a guinea pig model. We propose that retrograde transport from infected skin and viremia deliver VZV to neurons in which it becomes latent. Wild type (WT) VZV was found to be latent in many ganglia of vaccinated children with no history of varicella, suggesting that subclinical infection with WT-VZV occurs with subsequent viremic dissemination. The 30% to 40% rate of WT-VZV zoster reported in vaccinees and occasional trigeminal zoster due to vaccine type VZV (vOka) are consistent with viremic delivery of VZV to multiple ganglia. Most human intestinal specimens contained latent VZV within neurons of the enteric nervous system (ENS). Induction of viremia in guinea pigs led to VZV latency throughout the ENS. The possibility VZV reactivation in the ENS is an unsuspected cause of gastrointestinal disease requires future investigation. PMID:23303966

Zoster Vaccination Increases the Breadth of CD4+ T Cells Responsive to Varicella Zoster Virus

PubMed Central

Laing, Kerry J.; Russell, Ronnie M.; Dong, Lichun; Schmid, D. Scott; Stern, Michael; Magaret, Amalia; Haas, Jürgen G.; Johnston, Christine; Wald, Anna; Koelle, David M.

2015-01-01

Background. The live, attenuated varicella vaccine strain (vOka) is the only licensed therapeutic vaccine. Boost of varicella zoster virus (VZV)–specific cellular immunity is a likely mechanism of action. We examined memory CD4+ T-cell responses to each VZV protein at baseline and after zoster vaccination. Methods. Serial blood samples were collected from 12 subjects vaccinated with Zostavax and immunogenicity confirmed by ex vivo VZV-specific T-cell and antibody assays. CD4+ T-cell lines enriched for VZV specificity were generated and probed for proliferative responses to every VZV protein and selected peptide sets. Results. Zoster vaccination increased the median magnitude (2.3-fold) and breadth (4.2-fold) of VZV-specific CD4+ T cells one month post-vaccination. Both measures declined by 6 months. The most prevalent responses at baseline included VZV open reading frames (ORFs) 68, 4, 37, and 63. After vaccination, responses to ORFs 40, 67, 9, 59, 12, 62, and 18 were also prevalent. The immunogenicity of ORF9 and ORF18 were confirmed using peptides, defining a large number of discrete CD4 T-cell epitopes. Conclusions. The breadth and magnitude of the VZV-specific CD4+ T-cell response increase after zoster vaccination. In addition to glycoprotein E (ORF68), we identified antigenic ORFs that may be useful components of subunit vaccines. PMID:25784732

Comparing the quality of pro- and anti-vaccination online information: a content analysis of vaccination-related webpages.

PubMed

Sak, Gabriele; Diviani, Nicola; Allam, Ahmed; Schulz, Peter J

2016-01-15

The exponential increase in health-related online platforms has made the Internet one of the main sources of health information globally. The quality of health contents disseminated on the Internet has been a central focus for many researchers. To date, however, few comparative content analyses of pro- and anti-vaccination websites have been conducted, and none of them compared the quality of information. The main objective of this study was therefore to bring new evidence on this aspect by comparing the quality of pro- and anti-vaccination online sources. Based on past literature and health information quality evaluation initiatives, a 40-categories assessment tool (Online Vaccination Information Quality Codebook) was developed and used to code a sample of 1093 webpages retrieved via Google and two filtered versions of the same search engine. The categories investigated were grouped into four main quality dimensions: web-related design quality criteria (10 categories), health-specific design quality criteria (3 categories), health related content attributes (12 categories) and vaccination-specific content attributes (15 categories). Data analysis comprised frequency counts, cross tabulations, Pearson's chi-square, and other inferential indicators. The final sample included 514 webpages in favor of vaccination, 471 against, and 108 neutral. Generally, webpages holding a favorable view toward vaccination presented more quality indicators compared to both neutral and anti-vaccination pages. However, some notable exceptions to this rule were observed. In particular, no differences were found between pro- and anti-vaccination webpages as regards vaccination-specific content attributes. Our analyses showed that the overall quality of pro-vaccination webpages is superior to anti-vaccination online sources. The developed coding scheme was proven to be a helpful and reliable tool to judge the quality of vaccination-related webpages. Based on the results, we advance

Efficacy of varicella (VZV) vaccination: an update for the clinician

PubMed Central

Wang, Lili; Zhu, Lucy; Zhu, Hua

2016-01-01

Varicella-zoster virus (VZV) infection causes two distinct clinical conditions. Primary varicella infection results in chickenpox, a contagious rash illness typically seen among children. VZV can reactivate years after the initial infection to cause herpes zoster (HZ) and lead to post-herpetic neuralgia, a common complication resulting in persistent pain that may last for years after the zoster rash resolves. A person’s risk of having longer lasting and more severe pain associated with HZ increases with age. Since the introduction of VZV vaccines, the rates of infection, hospitalizations, and mortality have declined. In this review, we discuss in detail current VZV vaccines available for the prevention of VZV and HZ infections. Varilrix (GSK Biologicals, UK), Varivax (Merck, USA) and the combined measles, mumps, rubella, and varicella (MMRV) vaccine contain the live attenuated Oka strain of VZV for routine varicella vaccination. While Zostavax is the only HZ vaccine currently approved for use in the United States and the European Union [EMEA, 2011], a subunit vaccine candidate called HZ/su has recently shown improved efficacy for zoster prevention in two clinical trial phase III studies. VariZIG, a post-exposure prophylactic, uses zoster immune globulin to prevent VZV infection in those who have recently been in contact with VZV but lack evidence of varicella immunity and are contraindicated to receive the varicella vaccine. Further, we discuss the skin tropic and neurotropic factor VZV ORF7 gene and its involvement in varicella infection, reactivation and latency in ganglia. Ultimately, these studies can contribute to the development of a neuroattenuated vaccine candidate against varicella or a vector for delivery of other virus antigens. PMID:27551429

Reactogenicity of infant whole cell pertussis combination vaccine compared with acellular pertussis vaccines with or without simultaneous pneumococcal vaccine in the Netherlands.

PubMed

David, Silke; Vermeer-de Bondt, Patricia E; van der Maas, Nicoline A T

2008-10-29

In addition to the routine enhanced passive safety surveillance of the Dutch National Vaccination Programme, RIVM (National Institute for Public Health and the Environment) started a large questionnaire study enrolling approximately 53,000 children from December 2003 until September 2007. We intended to establish accurate frequency estimates for several more severe adverse events and to compare the incidence rates of three different infant vaccines that were used consecutively. Whole cell pertussis (wP) DTP-IPV-Hib vaccine (NVI) was replaced by acellulair pertussis (aP) in 2005, first Infanrix-IPV-Hib (GSK) followed by Pediacel (Sanofi) in 2006. Pneumococcal vaccine, Prevenar (Wyeth), was added for children born from April 2006. Parents returned 28,796 questionnaires (response 54%), 15,069 for whole cell pertussis and 13,727 for acellular pertussis vaccine, including 4485 with pneumococcal vaccine. The OR for reported events was 3-6 for whole cell pertussis vaccine compared with acellular vaccine. This was true for prolonged crying for 3h and more after the first dose (1.5% versus 0.4%; 95 CI 1.1-1.9 and 95% CI 0.2-0.7, respectively), and very high fever of 40.5 degrees C and over following the fourth dose (0.8% versus 0.2%; 95% CI 0.5-1.1 and 0.06-0.3, respectively), while possible febrile convulsions were diagnosed only twice after the fourth dose in the whole cell vaccine group and one after acellular pertussis vaccine. Pallor was significantly more frequent after the first dose of whole cell pertussis than after acellulair pertussis vaccination (18.3% versus 3.4%; 95% CI 17.2-19.5 and 95% CI 2.8-4.0 respectively) Collapse after the first dose was rare in both vaccine groups (5 after whole cell vaccine and 1 after acellular vaccine). The addition of conjugated pneumococcal vaccine did not result in statistically significant increased rates of adverse events in the acellular vaccine group. Whole cell pertussis vaccine showed a significantly higher reactogenicity

Comparative performance of a licensed anthrax vaccine versus electroporation based delivery of a PA encoding DNA vaccine in rhesus macaques.

PubMed

Livingston, Brian D; Little, Stephen F; Luxembourg, Alain; Ellefsen, Barry; Hannaman, Drew

2010-01-22

DNA vaccination is a promising immunization strategy that could be applied in the development of vaccines for a variety of prophylactic and therapeutic indications. Utilizing anthrax protective antigen as a model antigen, we demonstrate that electroporation mediated delivery enhanced the immunogenicity of DNA vaccines in nonhuman primates over 100-fold as compared to conventional intramuscular injection. Two administrations of a DNA vaccine with electroporation elicited anthrax toxin neutralizing antibody responses in 100% of rhesus macaques. Toxin neutralizing antibodies were sustained for the nearly 1-year study duration and were correlated with protection against subsequent lethal Bacillus anthracis spore challenge. Collectively, electroporation mediated DNA vaccination conferred protection comparable to that observed following vaccination with an FDA approved anthrax vaccine.

Influenza Vaccination Strategies: Comparing Inactivated and Live Attenuated Influenza Vaccines

PubMed Central

Sridhar, Saranya; Brokstad, Karl A.; Cox, Rebecca J.

2015-01-01

Influenza is a major respiratory pathogen causing annual outbreaks and occasional pandemics. Influenza vaccination is the major method of prophylaxis. Currently annual influenza vaccination is recommended for groups at high risk of complications from influenza infection such as pregnant women, young children, people with underlying disease and the elderly, along with occupational groups such a healthcare workers and farm workers. There are two main types of vaccines available: the parenteral inactivated influenza vaccine and the intranasal live attenuated influenza vaccine. The inactivated vaccines are licensed from 6 months of age and have been used for more than 50 years with a good safety profile. Inactivated vaccines are standardized according to the presence of the viral major surface glycoprotein hemagglutinin and protection is mediated by the induction of vaccine strain specific antibody responses. In contrast, the live attenuated vaccines are licensed in Europe for children from 2–17 years of age and provide a multifaceted immune response with local and systemic antibody and T cell responses but with no clear correlate of protection. Here we discuss the immunological immune responses elicited by the two vaccines and discuss future work to better define correlates of protection. PMID:26343192

Productive vs non-productive infection by cell-free Varicella zoster virus of human neurons derived from embryonic stem cells is dependent upon infectious viral dose

PubMed Central

Sloutskin, Anna; Kinchington, Paul R.; Goldstein, Ronald S.

2013-01-01

Varicella Zoster virus (VZV) productively infects humans causing varicella upon primary infection and herpes zoster upon reactivation from latency in neurons. In-vitro studies using cell-associated VZV infection have demonstrated productive VZV-infection, while a few recent studies of human neurons derived from stem cells incubated with cell-free, vaccine-derived VZV did not result in generation of infectious virus. In the present study, 90%-pure human embryonic stem cell-derived neurons were incubated with recombinant cell-free pOka-derived made with an improved method or with VZV vaccine. We found that cell-free pOka and vOka at higher multiplicities of infection elicited productive infection in neurons followed by spread of infection, cytopathic effect and release of infectious virus into the medium. These results further validate the use of this unlimited source of human neurons for studying unexplored aspects of VZV interaction with neurons such as entry, latency and reactivation. PMID:23769240

Cost-effectiveness of HPV vaccination regime: comparing twice versus thrice vaccinations dose regime among adolescent girls in Malaysia.

PubMed

Aljunid, Syed; Maimaiti, Namaitijiang; Nur, Amrizal M; Noor, Mohd Rushdan Md; Wan Puteh, Sharifa Ezat

2016-01-23

The HPV vaccine was introduced to Malaysian national immunization programme in 2010. The current implementation age of HPV vaccination in Malaysian is at the age of 13 years school girls, given according to a 3 doses protocol which may complicate implementation and compliance. Aim of the study is to determine the cost-effectiveness of HPV vaccination regime comparing twice versus thrice HPV vaccinations dose regime among adolescent girls in Malaysia. A Markov cohort model reflecting the natural history of HPV infection accounting for oncogenic and low-risk HPV was adapted for 13 year old Malaysian girls cohort (n = 274,050). Transition probabilities, utilities values, epidemiological and cost data were sourced from published literature and local data. Vaccine effectiveness was based on overall efficacy reported from 3-doses clinical trials, with the assumption that the 2-doses is non-inferior to the 3-doses allowing overall efficacy to be inferred from the 3-doses immunogenicity data. Price parity and life-long protection were assumed. The payer perspective was adopted, with appropriate discounting for costs (3 %) and outcomes (3 %). One way sensitivity analysis was conducted. The sensitivity analysis on cost of vaccine, vaccine coverage and discount rate with a 2-doses protocol was performed. The 3-doses and 2-doses regimes showed same number of Cervical Cancers averted (361 cases); QALYs saved at 7,732,266. However, the lifetime protection under the 2-doses regime, showed a significant cost-savings of RM 36, 722,700 compared to the 3-doses scheme. The MOH Malaysia could vaccinate 137,025 more girls in this country using saving 2-doses regime vaccination programme. The model predicted that 2-doses HPV vaccination schemes can avoid additional 180 Cervical Cancers and 63 deaths compare to 3-doses. A 2-doses HPV vaccination scheme may enable Malaysian women to be protected at a lower cost than that achievable under a 3-doses scheme, while avoiding the same number of

Comparative study and evaluation of further attenuated, live measles vaccines alone and in combination with mumps and rubella vaccines.

PubMed

Wegmann, A; Glück, R; Just, M; Mischler, R; Paroz, P; Germanier, R

1986-01-01

The further attenuated Enders (FAE) measles vaccine strain and the Edmonston B-Zagreb (EZ) measles vaccine strain were compared. In VERO-cells plaque sizes of FAE varied between 0.5 and 1 mm, those of EZ between 1 and 2 mm in diameter. The lots available in Switzerland during a 2 year period showed virus titers of 10(3.1) to 10(4.0) TCID50 per dose in the one vaccine (FAE) and of 10(3.1) to 10(4.5) TCID50 per dose in the other (EZ). Clinical investigations were performed with FAE and EZ monovalent and trivalent (measles + mumps + rubella) vaccine preparations. The virus titers of the vaccine lots used were 10(3.1) to 10(4.0) TCID50 per dose. The overall seroconversion rates of 96% to 100% indicate that both types of vaccine have comparable immunization properties. Stability tests demonstrated good stability of both the FAE and the EZ vaccines. Thus conservation at 37 degrees C was possible for 2 and 4 weeks, respectively, and at 41 degrees C for 6 and 6 days, respectively, without undue loss of live virus content (less than 1 log 10). Since the EZ vaccine is derived from human diploid cells, it is particularly suitable for the vaccination of persons with a history of allergy to avian proteins.

Comparative cost effectiveness of varicella, hepatitis A, and pneumococcal conjugate vaccines.

PubMed

Jacobs, R J; Meyerhoff, A S

2001-12-01

Several state and local U.S. governments are considering making varicella, hepatitis A, and/or pneumococcal conjugate vaccination conditions of day care or school entry. These requirements will likely be issued sequentially, because simultaneous mandates exacerbate budget constraints and complicate communication with parents and providers. Cost-effectiveness assessments should aid the establishment of vaccination priorities, but comparing results of published studies is confounded by their dissimilar methods. We reviewed U.S. cost-effectiveness studies of childhood varicella, hepatitis A, and pneumococcal conjugate vaccines and identified four providing data required to standardize methods. Vaccination, disease treatment, and work-loss costs were estimated from original study results and current prices. Estimated life-years saved were derived from original study results, epidemiological evidence, and alternative procedures for discounting to present values. Hepatitis A vaccine would have the lowest health system costs per life-year saved. Varicella vaccine would provide the greatest reduction in societal costs, mainly through reduced parent work loss. Pneumococcal conjugate vaccine would cost twice the amount of varicella and hepatitis A vaccines combined and be less cost effective than the other vaccines. Hepatitis A and varicella vaccines, but not pneumococcal conjugate vaccine, meet or exceed conventional standards of cost effectiveness. Copyright 2001 American Health Foundation and Elsevier Science.

Virosomal hepatitis a vaccine: comparing intradermal and subcutaneous with intramuscular administration.

PubMed

Frösner, Gert; Steffen, Robert; Herzog, Christian

2009-01-01

Vaccination against hepatitis A virus (HAV) is unaffordable to many developing countries. Substantial reductions in cost occur when vaccines are administered intradermally at low doses. Aluminum-free HAV vaccines are considered more suitable for intradermal use than traditional vaccines which can cause long-lasting local reactions. Thus, we compared the immunogenicity and safety of an aluminum-free virosomal HAV vaccine (Epaxal) administered by different routes: intradermal (i.d.), subcutaneous (s.c.), and intramuscular (i.m.). Two open pilot studies were conducted as sub-studies of a large lot consistency trial. Healthy subjects aged 18 to 45 were enrolled. Study 1 compared two i.d. regimens of a lower dose of Epaxal [0.1 mL (4.8 IU), one or two injection sites] with i.m. administration of the standard dose [0.5 mL (24 IU)]. Study 2 compared the s.c. with the i.m. administration of the standard dose. At month 12, subjects in study 1 received a booster dose of 0.1 mL i.d. or 0.5 mL i.m.; subjects in study 2 received 0.5 mL via the respective route (s.c. or i.m.). Serum was tested for antibodies at baseline, 2 weeks (study 1), and 1 and 6 months after the primary vaccination as well as prior and 1 month after the booster dose. Incidences of solicited and unsolicited adverse events were recorded. Seroprotection rates (anti-HAV geometric mean concentration of > or =20 mIU/mL) after 1 month ranged from 93.2% to 100% in all groups and remained high until month 12 (range 85.2&-90.2%). Complete (100%) seroprotection was achieved by all subjects in all groups after booster vaccination. All routes of administration were well tolerated. Local reactions were more common in subjects vaccinated i.d. and s.c. than i.m. The aluminum-free virosomal HAV vaccine Epaxal is highly immunogenic and well tolerated when administered either via i.d., s.c., or i.m. Vaccination via the i.d. route may confer significant cost savings over the conventional i.m. route.

Adaptive immune responses to booster vaccination against yellow fever virus are much reduced compared to those after primary vaccination.

PubMed

Kongsgaard, Michael; Bassi, Maria R; Rasmussen, Michael; Skjødt, Karsten; Thybo, Søren; Gabriel, Mette; Hansen, Morten Bagge; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup; Buus, Soren; Stryhn, Anette

2017-04-06

Outbreaks of Yellow Fever occur regularly in endemic areas of Africa and South America frequently leading to mass vaccination campaigns straining the availability of the attenuated Yellow Fever vaccine, YF-17D. The WHO has recently decided to discontinue regular booster-vaccinations since a single vaccination is deemed to confer life-long immune protection. Here, we have examined humoral (neutralizing antibody) and cellular (CD8 and CD4 T cell) immune responses in primary and booster vaccinees (the latter spanning 8 to 36 years after primary vaccination). After primary vaccination, we observed strong cellular immune responses with T cell activation peaking ≈2 weeks and subsiding to background levels ≈ 4 weeks post-vaccination. The number of antigen-specific CD8+ T cells declined over the following years. In >90% of vaccinees, in vitro expandable T cells could still be detected >10 years post-vaccination. Although most vaccinees responded to a booster vaccination, both the humoral and cellular immune responses observed following booster vaccination were strikingly reduced compared to primary responses. This suggests that pre-existing immunity efficiently controls booster inoculums of YF-17D. In a situation with epidemic outbreaks, one could argue that a more efficient use of a limited supply of the vaccine would be to focus on primary vaccinations.

Significantly Reduced Genoprevalence of Vaccine-Type HPV-16/18 Infections among Vaccinated Compared to Non-Vaccinated Young Women 5.5 Years after a Bivalent HPV-16/18 Vaccine (Cervarix®) Pilot Project in Uganda

PubMed Central

Berggren, Vanja; Wabinga, Henry; Lillsunde-Larsson, Gabriella; Helenius, Gisela; Kaliff, Malin; Karlsson, Mats; Kirimunda, Samuel; Musubika, Caroline; Andersson, Sören

2016-01-01

The objective of this study was to determine the prevalence and some predictors for vaccine and non-vaccine types of HPV infections among bivalent HPV vaccinated and non-vaccinated young women in Uganda. This was a comparative cross sectional study 5.5 years after a bivalent HPV 16/18 vaccination (Cervarix®, GlaxoSmithKline, Belgium) pilot project in western Uganda. Cervical swabs were collected between July 2014-August 2014 and analyzed with a HPV genotyping test, CLART® HPV2 assay (Genomica, Madrid Spain) which is based on PCR followed by microarray for determination of genotype. Blood samples were also tested for HIV and syphilis infections as well as CD4 and CD8 lymphocyte levels. The age range of the participants was 15–24 years and mean age was 18.6(SD 1.4). Vaccine-type HPV-16/18 strains were significantly less prevalent among vaccinated women compared to non-vaccinated women (0.5% vs 5.6%, p 0.006, OR 95% CI 0.08(0.01–0.64). At type-specific level, significant difference was observed for HPV16 only. Other STIs (HIV/syphilis) were important risk factors for HPV infections including both vaccine types and non-vaccine types. In addition, for non-vaccine HPV types, living in an urban area, having a low BMI, low CD4 count and having had a high number of life time sexual partners were also significant risk factors. Our data concurs with the existing literature from other parts of the world regarding the effectiveness of bivalent HPV-16/18 vaccine in reducing the prevalence of HPV infections particularly vaccine HPV- 16/18 strains among vaccinated women. This study reinforces the recommendation to vaccinate young girls before sexual debut and integrate other STI particularly HIV and syphilis interventions into HPV vaccination packages. PMID:27482705

Post-licensure safety surveillance of zoster vaccine live (Zostavax®) in the United States, Vaccine Adverse Event Reporting System (VAERS), 2006-2015.

PubMed

Miller, Elaine R; Lewis, Paige; Shimabukuro, Tom T; Su, John; Moro, Pedro; Woo, Emily Jane; Jankosky, Christopher; Cano, Maria

2018-03-26

Herpes zoster (HZ), or shingles, is caused by reactivation of varicella-zoster virus in latently infected individuals. Live-attenuated HZ vaccine (zoster vaccine live, ZVL) is approved in the United States for persons aged ≥50 years and recommended by the CDC for persons ≥60 years. We analyzed U.S. reports of adverse events (AEs) following ZVL submitted to the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting system to monitor vaccine safety, for persons vaccinated May 1, 2006, through January 31, 2015. We conducted descriptive analysis, clinical reviews of reports with selected pre-specified conditions, and empirical Bayesian data mining. VAERS received 23,092 reports following ZVL, of which 22,120 (96%) were classified as non-serious. Of reports where age was documented (n = 18,817), 83% were in persons aged ≥60 years. Reporting rates of AEs were 106 and 4.4 per 100,000 ZVL doses distributed for all reports and serious reports, respectively. When ZVL was administered alone among persons aged ≥50 years, injection site erythema (27%), HZ (17%), injection site swelling (17%), and rash (14%) were the most commonly reported symptoms among non-serious reports; HZ (29%), pain (18%), and rash (16%) were the most commonly reported symptoms among serious reports. Six reports included laboratory evidence of vaccine-strain varicella-zoster virus (Oka/Merck strain) infection; AEs included HZ, HZ- or varicella-like illness, and local reaction with vesicles. In our review of reports of death with sufficient information to determine cause (n = 46, median age 75 years), the most common causes were heart disease (n = 28), sepsis (n = 4), and stroke (n = 3). Empirical Bayesian data mining did not detect new or unexpected safety signals. Findings from our safety review of ZVL are consistent with those from pre-licensure clinical trials and other post-licensure assessments. Transient injection-site reactions, HZ, and rashes were most frequently

Evaluation of efficacy and effectiveness of live attenuated zoster vaccine.

PubMed

Gabutti, G; Valente, N; Sulcaj, N; Stefanati, A

2014-12-01

Herpes zoster (HZ) is a viral disease characterized by a dermatologic and neurologic involvement caused by the reactivation of the latent varicella zoster virus (VZV) acquired during primary infection (varicella). HZ incidence increases with age and is related to waning specific cell-mediated immunity (CMI). The most frequent complication of HZ is post-herpetic neuralgia (PHN) characterized by chronic pain lasting at least 30 days, with impact on patients' quality of life. Available treatments are quite unsatisfactory in reducing pain and length of the disease. The evaluation of the epidemiology, the debilitating complications (PHN), the suboptimal available treatments and the costs related to the diagnosis and clinical/therapeutic management of HZ patients have been the rationale for the search of an adequate preventive measure against this disease. The target of this intervention is to reduce the frequency and severity of HZ and related complications by stimulating CMI. Prevention has recently become possible with the live attenuated vaccine Oka/Merck, with an antigen content at least 10-fold higher than the antigen content of pediatric varicella vaccines. Clinical studies show a good level of efficacy and effectiveness, particularly against the burden of illness and PHN in all age classes. Accordingly to the summary of the characteristics of the product the zoster vaccine is indicated for the prevention of HZ and PHN in individuals 50 years of age or older and is effective and safe in subjects with a positive history of HZ.

Public health and economic impact of seasonal influenza vaccination with quadrivalent influenza vaccines compared to trivalent influenza vaccines in Europe.

PubMed

Uhart, Mathieu; Bricout, Hélène; Clay, Emilie; Largeron, Nathalie

2016-09-01

Influenza B strains represent on average 23% of all circulating strains in Europe and when there is a vaccine mismatch on B strains, additional influenza-related hospitalizations and deaths as well as substantial additional costs are observed. The objective was to estimate the public health and economic impact of seasonal influenza vaccination with quadrivalent influenza vaccines (QIV) compared to trivalent influenza vaccines (TIV) in Europe (EU). Based on data from 5 EU countries (France, Germany, Italy, Spain and UK) during 10 influenza seasons from 2002 to 2013, epidemiological and associated economic outcomes were estimated for each season for the actual scenario where the TIV was used, and for a hypothetical scenario where QIV could have been used instead. By using QIV, this study estimated that for the 5 EU countries, an additional 1.03 million (327.9/100,000 inhabitants) influenza cases, 453,000 (143.9/100,000) general practitioners consultations, 672,000 (213.1/100,000) workdays lost, 24,000 (7.7/100,000) hospitalizations and 10,000 (3.1/100,000) deaths could have been avoided compared to the use of TIV over the 10-seasons-period. This study estimates that QIV can be of economic value since from a societal perspective 15 million Euros would have been saved on general practitioners consultations (14 million Euros from third-party payer perspective), 77 million on hospitalizations (74 million Euros from third-party payer perspective) and 150 million Euros on workdays lost, across the 5 EU countries. In conclusion, the present study estimates that, compared to TIV, QIV may result in a substantial decrease in epidemiological burden and in influenza-related costs.

Co-administration of live measles and yellow fever vaccines and inactivated pentavalent vaccines is associated with increased mortality compared with measles and yellow fever vaccines only. An observational study from Guinea-Bissau.

PubMed

Fisker, Ane Bærent; Ravn, Henrik; Rodrigues, Amabelia; Østergaard, Marie Drivsholm; Bale, Carlito; Benn, Christine Stabell; Aaby, Peter

2014-01-23

Studies from low-income countries indicate that co-administration of inactivated diphtheria-tetanus-pertussis (DTP) vaccine and live attenuated measles vaccine (MV) is associated with increased mortality compared with receiving MV only. Pentavalent (DTP-H. Influenza type B-Hepatitis B) vaccine is replacing DTP in many low-income countries and yellow fever vaccine (YF) has been introduced to be given together with MV. Pentavalent and YF vaccines were introduced in Guinea-Bissau in 2008. We investigated whether co-administration of pentavalent vaccine with MV and yellow fever vaccine has similar negative effects. In 2007-2011, we conducted a randomised placebo-controlled trial of vitamin A at routine vaccination contacts among children aged 6-23 months in urban and rural Guinea-Bissau. In the present study, we included 2331 children randomised to placebo who received live vaccines only (MV or MV+YF) or a combination of live and inactivated vaccines (MV+DTP or MV+YF+pentavalent). Mortality was compared in Cox proportional hazards models stratified for urban/rural enrolment adjusted for age and unevenly distributed baseline factors. While DTP was still used 685 children received MV only and 358 MV+DTP; following the change in programme, 940 received MV+YF only and 348 MV+YF+pentavalent. During 6 months of follow-up, the adjusted mortality rate ratio (MRR) for co-administered live and inactivated vaccines compared with live vaccines only was 3.24 (1.20-8.73). For MV+YF+pentavalent compared with MV+YF only, the adjusted MRR was 7.73 (1.79-33.4). In line with previous studies of DTP, the present results indicate that pentavalent vaccine co-administered with MV and YF is associated with increased mortality. Copyright © 2013 Elsevier Ltd. All rights reserved.

Comparative study of two human diploid rabies vaccines administered with antirabies globulin.

PubMed

Vodopija, I; Sureau, P; Smerdel, S; Lafon, M; Baklaic, Z; Ljubicic, M; Svjetlicic, M

1988-12-01

The association of human rabies immune globulin (HRIG) to the vaccine is recommended for postexposure rabies treatment in cases of severe exposure. In a previous study using an abbreviated postexposure vaccination schedule it was observed that passive immunization could partially inhibit the active immune response, with three cell-culture purified vaccines but not with the concentrated human diploid cell vaccine (HDCV). In order to see if this difference was related to the purification process, the present study was designed comparing two HDCV, one concentrated and the other concentrated and purified, both of them administered in association with HRIG. The neutralizing antibody response in the vaccines was found to be identical with both vaccines, ruling out the role of the purification and confirming the excellent immunogenicity of both human diploid cell vaccines and the absence of inhibition of the active immune response by the association of HRIG to HDCV.

A comparative analysis of vaccine administration in urban and non-urban skilled nursing facilities.

PubMed

Pu, Yuan; Dolar, Veronika; Gucwa, Azad L

2016-07-29

The U.S. population is aging at an unprecedented rate, resulting in an increased demand for skilled nursing facilities (SNFs) and long-term care. Residents of these facilities are at a high risk for pneumococcal disease or severe influenza-related illnesses and death. For these reasons, the Centers for Medicare and Medicaid Services use influenza and pneumococcal vaccination rates as a quality measure in the assessment of SNFs, as complications related to these infections increase morbidity and mortality rates. Disparities have been reported amongst vaccination with increased rates in urban areas as compared to their non-urban counterparts. Statistical analyses were performed to compare influenza and pneumococcal vaccination in urban and non-urban SNFs to determine variables that may influence vaccination status. Of the 15,639 nursing homes included in the study, 10,107 were in urban areas, while 5532 were considered non-urban. We found the percent of eligible and willing residents with up-to-date influenza and pneumococcal vaccinations increased with overall five-star ratings of SNFs. Somewhat paradoxically, although urban SNFs had higher mean overall five-star ratings, they showed lower rates of influenza and pneumococcal vaccination compared to non-urban SNFs. Ordinary least squares regression analysis comparing overall ratings, type of ownership, and geographic location by region yielded statistically significant results in which the overall rating, ownership-type and certificate-type favored urban SNFs (p < 0.001). This is the first systematic and comparative analysis to use the Nursing Home Compare database to assess vaccine administration of urban and non-urban SNFs. The findings of this study may be used to encourage the development of programs to improve vaccination rates and the quality of care in these facilities.

Comparative Immunogenicity of the Tetanus Toxoid and Recombinant Tetanus Vaccines in Mice, Rats, and Cynomolgus Monkeys.

PubMed

Yu, Rui; Fang, Ting; Liu, Shuling; Song, Xiaohong; Yu, Changming; Li, Jianmin; Fu, Ling; Hou, Lihua; Xu, Junjie; Chen, Wei

2016-06-25

Tetanus is caused by the tetanus neurotoxin (TeNT) and is one of the most dreaded diseases especially in the developing countries. The current vaccine against tetanus is based on an inactivated tetanus toxin, which is effective but has many drawbacks. In our previous study, we developed a recombinant tetanus vaccine based on protein TeNT-Hc, with clear advantages over the toxoid vaccine in terms of production, characterization, and homogeneity. In this study, the titers, growth extinction, and persistence of specific antibodies induced by the two types of vaccine in mice, rats, and cynomolgus monkeys were compared. The booster vaccination efficacy of the two types of vaccines at different time points and protection mechanism in animals were also compared. The recombinant tetanus vaccine induced persistent and better antibody titers and strengthened the immunity compared with the commercially available toxoid vaccine in animals. Our results provide a theoretical basis for the development of a safe and effective recombinant tetanus vaccine to enhance the immunity of adolescents and adults as a substitute for the current toxoid vaccine.

Comparative Immunogenicity of the Tetanus Toxoid and Recombinant Tetanus Vaccines in Mice, Rats, and Cynomolgus Monkeys

PubMed Central

Yu, Rui; Fang, Ting; Liu, Shuling; Song, Xiaohong; Yu, Changming; Li, Jianmin; Fu, Ling; Hou, Lihua; Xu, Junjie; Chen, Wei

2016-01-01

Tetanus is caused by the tetanus neurotoxin (TeNT) and is one of the most dreaded diseases especially in the developing countries. The current vaccine against tetanus is based on an inactivated tetanus toxin, which is effective but has many drawbacks. In our previous study, we developed a recombinant tetanus vaccine based on protein TeNT-Hc, with clear advantages over the toxoid vaccine in terms of production, characterization, and homogeneity. In this study, the titers, growth extinction, and persistence of specific antibodies induced by the two types of vaccine in mice, rats, and cynomolgus monkeys were compared. The booster vaccination efficacy of the two types of vaccines at different time points and protection mechanism in animals were also compared. The recombinant tetanus vaccine induced persistent and better antibody titers and strengthened the immunity compared with the commercially available toxoid vaccine in animals. Our results provide a theoretical basis for the development of a safe and effective recombinant tetanus vaccine to enhance the immunity of adolescents and adults as a substitute for the current toxoid vaccine. PMID:27348002

[Comparative immunogenicity of 2 antirabies vaccines in a 2-1-1 post-exposure vaccination schedule].

PubMed

Landry, P; Lazzaro, M; Darioli, R

1998-09-09

Few trials have compared the Purified Duck Embryo Vaccine (PDEV) and the Human Diploid Cell Vaccine (HDCV) in a post-exposure immunization schedule of 4 shots (2 on day 0 and 1 each on day 7 and 21, or 2-1-1 schedule). A retrospective analysis compared 10 patients with PEDV and 20 with HDCV, who had received the 2-1-1 schedule as well as 20 UI mg/kg of immune globulins on day 0. The median neutralizing antibody titers on day 21 (after 3 doses) and the median of maximum titers until day 90 were higher for HDCV than for PEDV (0.6 IU/ml versus 3.5 IU/ml [p < 0.04] and 2.5 IU/ml versus 5.8 IU/ml [p < 0.03] respectively). Seven patients had not reached the seroconversion titer of 0.5 IU/ml after 3 doses (day 21). These results differ from previous studies showing a 100% seroconversion rate on day 21, and suggest that more studies are required before these 2 vaccines can be used in the 2-1-1 schedule after severe exposure.

Cost-effectiveness analysis of HPV vaccination: comparing the general population with socially vulnerable individuals.

PubMed

Han, Kyu-Tae; Kim, Sun Jung; Lee, Seo Yoon; Park, Eun-Cheol

2014-01-01

After the WHO recommended HPV vaccination of the general population in 2009, government support of HPV vaccination programs was increased in many countries. However, this policy was not implemented in Korea due to perceived low cost-effectiveness. Thus, the aim of this study was to analyze the cost-utility of HPV vaccination programs targeted to high risk populations as compared to vaccination programs for the general population. Each study population was set to 100,000 people in a simulation study to determine the incremental cost-utility ratio (ICUR), then standard prevalence rates, cost, vaccination rates, vaccine efficacy, and the Quality-Adjusted Life-Years (QALYs) were applied to the analysis. In addition, sensitivity analysis was performed by assuming discounted vaccination cost. In the socially vulnerable population, QALYs gained through HPV vaccination were higher than that of the general population (General population: 1,019, Socially vulnerable population: 5,582). The results of ICUR showed that the cost of HPV vaccination was higher for the general population than the socially vulnerable population. (General population: 52,279,255 KRW, Socially vulnerable population: 9,547,347 KRW). Compared with 24 million KRW/QALYs as the social threshold, vaccination of the general population was not cost-effective. In contrast, vaccination of the socially vulnerable population was strongly cost-effective. The results suggest the importance and necessity of government support of HPV vaccination programs targeted to socially vulnerable populations because a targeted approach is much more cost-effective. The implementation of government support for such vaccination programs is a critical strategy for decreasing the burden of HPV infection in Korea.

Stochastic simulation model comparing distributions of STEC O157 faecal shedding prevalence between cattle vaccinated with type III secreted protein vaccines and non-vaccinated cattle.

PubMed

Vogstad, A R; Moxley, R A; Erickson, G E; Klopfenstein, T J; Smith, D R

2014-06-01

Pens of cattle with high Escherichia coli O157:H7 (STEC O157) prevalence at harvest may present a greater risk to food safety than pens of lower prevalence. Vaccination of live cattle against STEC O157 has been proposed as an approach to reduce STEC O157 prevalence in live cattle. Our objective was to create a stochastic simulation model to evaluate the effectiveness of pre-harvest interventions. We used the model to compare STEC O157 prevalence distributions for summer- and winter-fed cattle to summer-fed cattle immunized with a type III secreted protein (TTSP) vaccine. Model inputs were an estimate of vaccine efficacy, observed frequency distributions for number of animals within a pen, and pen-level faecal shedding prevalence for summer and winter. Uncertainty about vaccine efficacy was simulated using a log-normal distribution (mean = 58%, SE = 0.14). Model outputs were distributions of STEC O157 faecal pen prevalence of summer-fed cattle unvaccinated and vaccinated, and winter-fed cattle unvaccinated. The simulation was performed 5000 times. Summer faecal prevalence ranged from 0% to 80% (average = 30%). Thirty-six per cent of summer-fed pens had STEC O157 prevalence >40%. Winter faecal prevalence ranged from 0% to 60% (average = 10%). Seven per cent of winter-fed pens had STEC O157 prevalence >40%. Faecal prevalence for summer-fed pens vaccinated with a 58% efficacious vaccine product ranged from 0% to 52% (average = 13%). Less than one per cent of vaccinated pens had STEC O157 prevalence >40%. In this simulation, vaccination mitigated the risk of STEC O157 faecal shedding to levels comparable to winter, with the major effects being reduced average shedding prevalence, reduced variability in prevalence distribution, and a reduction in the occurrence of the highest prevalence pens. Food safety decision-makers may find this modelling approach useful for evaluating the value of pre-harvest interventions. © 2013 Blackwell Verlag GmbH.

Comparative efficacy of Rubini, Jeryl-Lynn and Urabe mumps vaccine in an Asian population.

PubMed

Ong, Gary; Goh, Kee Tai; Ma, Stefan; Chew, Suok Kai

2005-11-01

The comparative efficacy of the three mumps vaccine strains (Jeryl-Lynn, Urabe and Rubini) was conducted in an Asian population from data arising from an epidemiological investigation of seven institutional outbreaks of mumps in Singapore. Demographic information (gender, age, ethnic group), clinical presentation and vaccination history (date and place of mumps vaccination, type of mumps vaccine received) of all children who attended the six childcare centres and one primary school where outbreaks of 20 or more cases of mumps occurred in 1999 were collected. The attack rate of the unvaccinated group and the attack rates of the vaccine groups (for each vaccine strain) were determined and the vaccine efficacy of the three vaccines calculated. The vaccine efficacy of the Jeryl-Lynn strain, Urabe strain and Rubini strain mumps vaccine were 80.7, 54.4 and -55.3%, respectively. Rubini strain mumps vaccine conferred no protection and has since been deregistered in Singapore.

Measuring HPV vaccination coverage in Australia: comparing two alternative population-based denominators.

PubMed

Barbaro, Bianca; Brotherton, Julia M L

2015-08-01

To compare the use of two alternative population-based denominators in calculating HPV vaccine coverage in Australia by age groups, jurisdiction and remoteness areas. Data from the National HPV Vaccination Program Register (NHVPR) were analysed at Local Government Area (LGA) level, by state/territory and by the Australian Standard Geographical Classification Remoteness Structure. The proportion of females vaccinated was calculated using both the ABS ERP and Medicare enrolments as the denominator. HPV vaccine coverage estimates were slightly higher using Medicare enrolments than using the ABS estimated resident population nationally (70.8% compared with 70.4% for 12 to 17-year-old females, and 33.3% compared with 31.9% for 18 to 26-year-old females, respectively.) The greatest differences in coverage were found in the remote areas of Australia. There is minimal difference between coverage estimates made using the two denominators except in Remote and Very Remote areas where small residential populations make interpretation more difficult. Adoption of Medicare enrolments for the denominator in the ongoing program would make minimal, if any, difference to routine coverage estimates. © 2015 Public Health Association of Australia.

Randomized trial to compare the safety and immunogenicity of CSL Limited's 2009 trivalent inactivated influenza vaccine to an established vaccine in United States children.

PubMed

Brady, Rebecca C; Hu, Wilson; Houchin, Vonda G; Eder, Frank S; Jackson, Kenneth C; Hartel, Gunter F; Sawlwin, Daphne C; Albano, Frank R; Greenberg, Michael

2014-12-12

A trivalent inactivated influenza vaccine (CSL's TIV, CSL Limited) was licensed under USA accelerated approval regulations for use in persons≥18 years. We performed a randomized, observer-blind study to assess the safety and immunogenicity of CSL's TIV versus an established US-licensed vaccine in a population≥6 months to <18 years of age. Subjects were stratified as follows: Cohort A (≥6 months to <3 years); Cohort B (≥3 years to <9 years); and Cohort C (≥9 years to <18 years). The subject's age and influenza vaccination history determined the dosing regimen (one or two vaccinations). Subjects received CSL's TIV (n=739) or the established vaccine (n=735) in the autumn of 2009. Serum hemagglutination-inhibition titers were determined pre-vaccination and 30 days after the last vaccination. No febrile seizures or other vaccine-related SAEs were reported. After the first vaccination for Cohorts A and B, respectively, the relative risks of fever were 2.73 and 2.32 times higher for CSL's TIV compared to the established vaccine. Irritability and loss of appetite (for Cohort A) and malaise (for Cohort B) were also significantly higher for CSL's TIV compared to the established vaccine. Post-vaccination geometric mean titers (GMTs) for CSL's TIV versus the established vaccine were 385.49 vs. 382.45 for H1N1; 669.13 vs. 705.61 for H3N2; and 100.65 vs. 93.72 for B. CSL's TIV demonstrated immunological non-inferiority to the established vaccine in all cohorts. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Health Economic Impact of Universal Infant Vaccination with the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine as Compared with 13-Valent Pneumococcal Conjugate Vaccine in Hong Kong.

PubMed

Lee, Kenneth K C; Chia Wu, David Bin; Topachevskyi, Oleksandr; Delgleize, Emmanuelle; DeAntonio, Rodrigo

2013-05-01

Pneumococcal universal vaccination in Hong Kong was introduced in 2009. We assessed the health and economic impact of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PCV-10) compared with the current 13-valent pneumococcal conjugate vaccine (PCV-13) recommended for Hong Kong in 2011, providing new elements to be considered by public health authorities in the future decision-making process for pneumococcal vaccines in this country. An analytical model was used to estimate the annual economic and health outcomes of invasive pneumococcal disease (IPD), community-acquired pneumonia, and acute otitis media (AOM), including nontypeable H. influenzae-related AOM, for a birth cohort in Hong Kong from the payer perspective with a 10-year horizon. Clinical impact including morbidity-mortality, quality-adjusted life-years (QALYs), incremental costs, and cost-effectiveness comparing PCV-10 and PCV-13 were estimated. Probabilistic sensitivity analyses by using alternate scenarios were performed. Model projections indicate that PCV-13 and PCV-10 have approximately equivalent impact on the prevention of deaths caused by IPD and pneumonia. PCV-13 is projected to prevent 6 additional cases of IPD, whereas PCV-10 is projected to prevent 13,229 additional AOM cases and 101 additional QALYs. For the base case, PCV-10 vaccination is estimated to save 44.6 million Hong Kong dollars (34.1 million Hong Kong dollars discounted). Sensitivity analysis indicated that PCV-10 would generate more QALYs and save costs as compared with PCV-13. Universal infant vaccination with new available pneumococcal vaccines is expected to generate a significant additional impact on reducing the burden of pneumococcal diseases in Hong Kong. PCV-10 vaccination would be potentially a cost-saving strategy compared with PCV-13 vaccination, generating better cost offsets and higher QALY gains. Copyright © 2013 International Society for Pharmacoeconomics and Outcomes

Comparative assessment of immunization coverage of migrant children between national immunization program vaccines and non-national immunization program vaccines in East China.

PubMed

Hu, Yu; Luo, Shuying; Tang, Xuewen; Lou, Linqiao; Chen, Yaping; Guo, Jing

2015-01-01

This study aimed to describe the disparities in immunization coverage between National Immunization Program (NIP) vaccines and non-NIP vaccines in Yiwu and to identify potential determinants. A face-to-face interview-based questionnaire survey among 423 migrant children born from 1 June 2010 to 31 May 2013 was conducted. Immunization coverage was estimated according to the vaccines scheduled at different age, the birth cohorts, and socio- demographic characteristics. Single-level logistic regression analysis was applied to identify the determinants of coverage of non-NIP vaccines. We found that NIP vaccines recorded higher immunization coverage compared with non-NIP vaccines (87.9100%- vs 0%-74.8%). Among the non-NIP vaccines, varicella vaccine (VarV) recorded the highest coverage of 85.4%, which was introduced in 1998; while 7-valent pneumococcal conjugate vaccine(PCV7) recorded the lowest coverage of 0% for primary series, which was introduced recently. Lower coverage rate of non-NIP vaccines was significantly associated with more siblings in household, shorter duration of living in the surveyed areas, lower family income, mother with a job, mother with poor awareness of vaccination, and mother with lower education level. We found the immunization coverage rate of non-NIP vaccines was significant lower than that of NIP vaccines. Expansion of NIP to include non-NIP vaccines can provide better protection against the vaccine preventable diseases through increased immunization coverage.

Vaccination Rates among Adolescents in Minnesota as Compared with the United States: Not "Above Average".

PubMed

Jacobson, Robert M; Rogacki, Brianna; Thompson, David M; Roberts, James R; Margolis, Benyamin; Darden, Paul M

2015-01-01

Because adolescents make relatively few visits to clinics for preventive care, their vaccination rates suffer. We examined rates among Minnesota youths to see how they compared with those among teens throughout the United States. We used National Immunization Survey-Teen (NIS-Teen) data to estimate vaccination rates for 13- to 17-year-olds in Minnesota from 2008 through 2013 and compared them to national rates for MCV4, Tdap and HPV vaccines. We also examined rates of provider recommendation for each of the three vaccines and rates of parental intention to vaccinate against HPV. We found rates for all three vaccinations increased between 2008 and 2013, but they continue to be low for both MCV4 (69%) and HPV (38% of females and 9% of males completed the three-dose series in 2013). Fortunately, the percentage of Minnesota clinicians recommending those vaccines is increasing (the percentage recommending HPV vaccination for females increased from 55% in 2008 to 74% in 2013; however, only 44% recommended it for males in 2013). The percentage of parents in Minnesota reporting intent to vaccinate their female children against HPV rose from 52% in 2008 to 58% in 2013; the percentage intending to vaccinate their male children rose from 16% in 2010 to 47% in 2013. Clinicians and public health officials must address how we can improve HPV vaccination rates among adolescents.

Updated data on effective and safe immunizations with live-attenuated vaccines for children after living donor liver transplantation.

PubMed

Shinjoh, Masayoshi; Hoshino, Ken; Takahashi, Takao; Nakayama, Tetsuo

2015-01-29

Although immunizations using live-attenuated vaccines are not recommended for children post-liver transplant due to their theoretical risks, they will inevitably encounter vaccine-preventable viral diseases upon returning to real-life situations. The window of opportunity for vaccination is usually limited prior to transplantation because these children often have unstable disease courses. Also, vaccine immunity does not always persist after transplantation. Beginning in 2002, subcutaneous immunizations with four individual live-attenuated vaccines (measles, rubella, varicella, and mumps) to pediatric patients following living donor liver transplantation (LDLT) were performed for those who fulfilled the clinical criteria, including humoral and cell-mediated immunity. Written informed consent was collected. We included the study on 70 immunizations for 18 cases that we reported in 2008 (Shinjoh et al., 2008). A total of 196 immunizations were administered to 48 pediatric post-LDLT recipients. Of these, 144 were first immunizations and 52 were repeated immunizations following LDLT. The seroconversion rates at the first dose for measles (AIK-C), rubella (TO-336), varicella (Oka), and mumps (Hoshino) were 100% (36/36), 100% (35/35), 70% (23/33), and 75% (24/32), respectively. Antibody levels did not fall over time in patients immunized with rubella vaccine. Three mild cases of breakthrough varicella were observed. Two cases with transient parotid gland swelling were observed after mumps immunization. Two admissions because of fever at 2-3 weeks after the measles vaccine were reported but the patients had no symptoms of measles. Immunizations using selected live-attenuated vaccines were safe and effective for post-LDLT children who were not severely immunosuppressed. However, with the exception of rubella, repeated immunization may be necessary. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparative assessment of immunization coverage of migrant children between national immunization program vaccines and non-national immunization program vaccines in East China

PubMed Central

Hu, Yu; Luo, Shuying; Tang, Xuewen; Lou, Linqiao; Chen, Yaping; Guo, Jing

2015-01-01

This study aimed to describe the disparities in immunization coverage between National Immunization Program (NIP) vaccines and non-NIP vaccines in Yiwu and to identify potential determinants. A face-to-face interview-based questionnaire survey among 423 migrant children born from 1 June 2010 to 31 May 2013 was conducted. Immunization coverage was estimated according to the vaccines scheduled at different age, the birth cohorts, and socio- demographic characteristics. Single-level logistic regression analysis was applied to identify the determinants of coverage of non-NIP vaccines. We found that NIP vaccines recorded higher immunization coverage compared with non-NIP vaccines (87.9100%– vs 0%-74.8%). Among the non-NIP vaccines, varicella vaccine (VarV) recorded the highest coverage of 85.4%, which was introduced in 1998; while 7-valent pneumococcal conjugate vaccine(PCV7) recorded the lowest coverage of 0% for primary series, which was introduced recently. Lower coverage rate of non-NIP vaccines was significantly associated with more siblings in household, shorter duration of living in the surveyed areas, lower family income, mother with a job, mother with poor awareness of vaccination, and mother with lower education level. We found the immunization coverage rate of non-NIP vaccines was significant lower than that of NIP vaccines. Expansion of NIP to include non-NIP vaccines can provide better protection against the vaccine preventable diseases through increased immunization coverage. PMID:25760670

Comparing live attenuated and inactivated hepatitis A vaccines: an immunogenicity study after one single dose.

PubMed

Zheng, Hui; Chen, Yuansheng; Wang, Fuzhen; Gong, Xiaohong; Wu, Zhenhua; Miao, Ning; Zhang, Xiaoshu; Li, Hui; Chen, Chao; Hou, Xiang; Cui, Fuqiang; Wang, Huaqing

2011-11-08

While three types of hepatitis A vaccines are available in China, little data are available to compare them in terms of early antibody response. We conducted a trial to compare antibody response at 7, 14 and 28 days. We randomized primary school children in Gansu and Jilin provinces into four groups to receive either (1) Chinese live attenuated hepatitis A vaccine (H2 strain), (2) domestic inactivated hepatitis A vaccine (Healive(®)), (3) imported inactivated hepatitis A vaccine (Havrix(®)) or (4) hepatitis B vaccine (Control group). We compared groups at 7, 14 and 28 days in terms of proportion of sero-conversions (≥10 mUI/ml), and Geometric Mean Concentration (GMC) of antibodies measured with a Microparticle Enzyme Immunoassay (MEIA). We compared rates of self-reported adverse events following immunization (AEFI) in the first three days. 204 children received the H2 vaccine, 208 received Healive(®), 214 received Havrix(®), and 215 received hepatitis B vaccine (no differences across groups in terms of age, sex, weight and height). At seven days, sero-conversion proportions were 25%, 35%, 27% and 2% (p<0.0001) with GMC of 6 mIU/ml, 8 mIU/ml, 6 mIU/ml and 3 mIU/ml, respectively for the four groups. At 28 days, sero-conversion proportions were 98%, 100%, 93% and 3% (p<0.0001) with GMC of 47 mIU/ml, 71 mIU/ml, 67 mIU/ml and 3 mIU/ml, respectively. AEFI were benign and did not differ across groups (p=0.94). While our study was not able to identify differences between Havrix(®), Healive(®) and H2 vaccine in terms of sero-conversion proportion and GMC between seven and 28 days, further studies should evaluate non-inferiority or equivalence of the Chinese vaccines, particularly with respect to the GMC concentration for the H2 vaccine since it could affect long-term protection. Copyright © 2011 Elsevier Ltd. All rights reserved.

Long Term Persistence of IgE Anti-Varicella Zoster Virus in Pediatric and Adult Serum Post Chicken Pox Infection and after Vaccination with Varicella Virus Vaccine.

PubMed

Smith-Norowitz, Tamar A; Josekutty, Joby; Silverberg, Jonathan I; Lev-Tov, Hadar; Norowitz, Yitzchok M; Kohlhoff, Stephan; Nowakowski, Maja; Durkin, Helen G; Bluth, Martin H

2009-12-01

The production of IgE specific to different viruses (HIV-1, Parvovirus B19, RSV), and the ability for IgE anti-HIV-1 to suppress HIV-1 production in vitro, strongly suggest an important role for IgE and/or anti viral specific IgE in viral pathogenesis. Previous studies in our laboratory were the first to report the presence of IgE anti-varicella zoster virus (VZV) in an adolescent patient with shingles. However, the presence and long term persistence of IgE anti VZV antibodies has not been studied in adults. The presence of serum IgE in addition to IgE and IgG anti-VZV antibody in sera were studied in children (N=12) (0-16 y/o) and adults (N=9) (32-76 y/o) with either a past history of (wild type) chicken pox (N=7 children, 9 adults) or 5 years after vaccination with varicella zoster (N=2 children) (Varicella virus vaccine live, Oka/Merck), as well as in non-infected subjects (N=3 children). Of the patients who had a positive history of chicken pox 13 of 16 (81%) contained IgE anti-VZV antibodies; they were both serum IgEHi (>100 IU/ml) and IgELo (<100 IU/ml). Of the patients who were vaccinated, IgE anti-VZV antibodies were undetected. In contrast, serum from the patients without a history of chicken pox or vaccination did not make either IgE or IgG anti-VZV antibodies. This is the first demonstration of the existence of IgE anti-VZV antibodies, and its long-term persistence in serum of previously infected subjects. Future studies regarding the functional role of anti-viral IgE and its relationship to VZV are warranted.

Cost-effectiveness analysis of the bivalent compared with the quadrivalent human papillomavirus vaccines in Taiwan.

PubMed

Demarteau, Nadia; Tang, Chao-Hsiun; Chen, Hui-Chi; Chen, Chien-Jen; Van Kriekinge, Georges

2012-01-01

To compare the epidemiological and economic impact of additional cross-protection against oncogenic human papillomavirus (HPV) types beyond 16/18 of the bivalent vaccine (BV) versus protection against nononcogenic HPV types 6/11 of the quadrivalent vaccine (QV) in Taiwan. A lifetime Markov model calibrated to the Taiwanese setting simulated the natural history of low-risk (engendering cervical intraepithelial neoplasia [CIN] 1 and genital warts) and high-risk HPV (engendering CIN1, CIN2/3, and cervical cancer [CC]) infections, screening, and vaccination (100% coverage) for a cohort of 12-year-old girls (N = 153,000). Transition probabilities, costs, and utilities were estimated from published data and expert opinion. Vaccine efficacy was obtained from each vaccine's respective clinical trials. Price-parity and lifelong protection was assumed for both vaccines. The number of CIN lesions, CC cases, CC deaths and genital wart (GW) cases, and quality-adjusted life-years were estimated. Costs and outcomes (discounted at 3% and 1.5%, respectively) were compared from a payer's perspective. The model estimated that the BV led to an additional, undiscounted, 11,484 CIN1, 1,779 (+34.3% vs. QV) CIN2/3, 188 (+29.0% vs. QV) CC, and 69 (+29.0% vs. QV) CC deaths prevented compared with the QV, while the QV prevented 4,150 GW (+71%). This resulted in an additional 768 quality-adjusted life-years (QALY) and 11.6 million new Taiwan dollars costs saved for the BV versus the QV after discounting. Both vaccines have a different epidemiological impact with an increased number of CC-related lesions potentially prevented for the BV because of additional cross-protection. In the Taiwanese setting, HPV mass vaccination using the BV was estimated to dominate vaccination using the QV. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Safety and immunogenicity of an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, compared with licensed vaccines in adults in Latin America.

PubMed

Stamboulian, D; Lopardo, G; Lopez, P; Cortes-Barbosa, C; Valencia, A; Bedell, L; Karsten, A; Dull, P M

2010-10-01

This study compared the investigational quadrivalent meningococcal CRM₁₉₇ conjugate vaccine, MenACWY-CRM, with licensed quadrivalent polysaccharide (MPSV4) and conjugate (MenACWY-D) meningococcal vaccines. In this phase III multicenter study, 2505 adults (aged 19-55 years) were randomized to receive either MenACWY-CRM or MenACWY-D, and 326 adults (aged 56-65 years) were randomized to receive either MenACWY-CRM or MPSV4. Sera obtained pre-vaccination and at 1-month post-vaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA) for immunogenicity non-inferiority and superiority analyses. The vaccines in all groups were well tolerated. In the 19-55 years age group, post-vaccination geometric mean titers (GMTs) were consistently higher for MenACWY-CRM than for MenACWY-D for all four serogroups. MenACWY-CRM was non-inferior to MenACWY-D for all serogroups, and superior for serogroup Y. In the 56-65 years age group, post-vaccination GMTs were 1.2- to 5.4-fold higher for MenACWY-CRM than for MPSV4 for the four serogroups. MenACWY-CRM is well tolerated and immunogenic in adults aged 19-65 years, with at least non-inferior immunogenicity compared with the currently licensed meningococcal vaccines. Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Safety and immunogenicity of a quadrivalent inactivated influenza vaccine compared to licensed trivalent inactivated influenza vaccines in adults.

PubMed

Greenberg, David P; Robertson, Corwin A; Noss, Michael J; Blatter, Mark M; Biedenbender, Rex; Decker, Michael D

2013-01-21

To evaluate the safety and immunogenicity of a prototype quadrivalent inactivated influenza vaccine (QIV) containing two influenza B strains, one of each lineage, compared with licensed trivalent inactivated influenza vaccines (TIVs) containing either a Victoria B-lineage strain (2009-2010 TIV) or a Yamagata B-lineage strain (2008-2009 TIV). Healthy adults ≥18 years of age were eligible to participate in this phase II, open-label, randomized, controlled, multicenter study conducted in the US. Participants received a single dose of 2009-2010 TIV, 2008-2009 TIV, or QIV. Sera were collected before and 21 days after vaccine administration to test for hemagglutination inhibition (HAI) antibodies to each of the four influenza strains. Immunogenicity endpoints included geometric mean HAI antibody titers (GMTs) and rates of seroprotection (titer ≥1:40) and seroconversion (4-fold rise pre- to post-vaccination). Safety endpoints included frequency of solicited injection-site and systemic reactions occurring within 3 days of vaccination, and unsolicited non-serious adverse events (AEs) and serious AEs (SAEs) within 21 days of vaccination. One hundred and ninety participants were enrolled to each vaccine group. QIV induced GMTs to each A and B strain that were noninferior to those induced by the 2009-2010 and 2008-2009 TIVs (i.e., lower limit of the two-sided 95% confidence interval of the ratio of GMT(QIV)/GMT(TIV)>0.66 for each strain). Rates of seroprotection and seroconversion were similar in all groups. Incidence and severity of solicited injection-site and systemic reactions, AEs, and SAEs were similar among groups. QIV, containing two B strains (one from each B lineage), was as safe and immunogenic as licensed TIV. QIV has the potential to be a useful alternative to TIV and offer protection against both B lineages. Copyright © 2012 Elsevier Ltd. All rights reserved.

AS03-Adjuvanted, Very-Low-Dose Influenza Vaccines Induce Distinctive Immune Responses Compared to Unadjuvanted High-Dose Vaccines in BALB/c Mice

PubMed Central

Yam, Karen K.; Gupta, Jyotsana; Winter, Kaitlin; Allen, Elizabeth; Brewer, Angela; Beaulieu, Édith; Mallett, Corey P.; Burt, David S.; Ward, Brian J.

2015-01-01

During the 2009–2010 influenza pandemic, an adjuvanted, dose-sparing vaccine was recommended for most Canadians. We hypothesize that differences exist in the responses to AS03-adjuvanted, low antigen (Ag) dose versus unadjuvanted, full-dose vaccines. We investigated the relationship between Ag dose and the oil-in-water emulsion Adjuvant System AS03. BALB/c mice received two IM doses of AS03A or AS03B with exaggerated dilutions of A/Uruguay/716/2007 H3N2 split virion vaccine Ag. Immune responses were assessed 3 weeks after the booster. Unadjuvanted “high” (3 μg) and low-dose (0.03–0.003 μg) vaccines generated similar serum antibody titers and cytokine secretion patterns in restimulated splenocytes. Compared to unadjuvanted “high-dose” vaccination, both AS03A and AS03B-adjuvanted low-dose vaccines tended to elicit higher serum antibody titers, broader induction of cytokine secretion and generated more influenza-specific antibody secreting cells and cytokine-secreting CD4 and CD8 T cells in splenocytes. We show that varying Ag and/or AS03 dose in this influenza vaccination mouse model can strongly influence both the magnitude and pattern of the immune response elicited. These findings are highly relevant given the likelihood of expanded use of adjuvanted, dose-sparing vaccines and raise questions about the use of “standard” doses of vaccines in pre-clinical vaccine studies. PMID:25972874

Comparing vaccines: a systematic review of the use of the non-inferiority margin in vaccine trials.

PubMed

Donken, R; de Melker, H E; Rots, N Y; Berbers, G; Knol, M J

2015-03-17

Non-inferiority (NI) randomized controlled trials (RCTs) aim to demonstrate that a new treatment is no worse than a comparator that has already shown its efficacy over placebo within a pre-specified margin. However, clear guidelines on how the NI margin should be determined are lacking for vaccine trials. A difference (seroprevalence/risk) of 10% or a geometric mean titre/concentration (GMT) ratio of 1.5 or 2.0 in antibody levels is implicitly recommended for vaccine trials. We aimed to explore which NI margins were used in vaccine RCTs and how they were determined. A systematic search for NI vaccine RCTs yielded 177 eligible articles. Data were extracted from these articles using a standardized form and included general characteristics and characteristics specific for NI trials. Relations between the study characteristics and the NI margin used were explored. Among the 143 studies using an NI margin based on difference (n=136 on immunogenicity, n=2 on efficacy and n=5 on safety), 66% used a margin of 10%, 23% used margins lower than 10% (range 1-7.5%) and 11% used margins larger than 10% (range 11.5-25%). Of the 103 studies using a NI margin based on the GMT ratio, 50% used a margin of 0.67/1.5 and 49% used 0.5/2.0. As observed, 85% of the studies did not discuss the method of margin determination; and 19% of the studies lacked a confidence interval or p-value for non-inferiority. Most NI vaccine RCTs used an NI margin of 10% for difference or a GMT ratio of 1.5 or 2.0 without a clear rationale. Most articles presented enough information for the reader to make a judgement about the NI margin used and the conclusions. The reporting on the design, margins used and results of NI vaccine trials could be improved; more explicit guidelines may help to achieve this end. Copyright © 2015 Elsevier Ltd. All rights reserved.

Exploring human papillomavirus vaccination refusal among ethnic minorities in England: A comparative qualitative study

PubMed Central

Rockliffe, Lauren; Marlow, Laura A.V.; Bedford, Helen; McBride, Emily; Waller, Jo

2017-01-01

Abstract Objectives In England, uptake of human papillomavirus (HPV) vaccination to prevent HPV‐related cancer is lower among girls from ethnic minority backgrounds. We aimed to explore the factors that prevented ethnic minority parents from vaccinating, compared to White British nonvaccinating parents and vaccinating ethnic minority parents. Methods Interviews with 33 parents (n = 14 ethnic minority non‐vaccinating, n = 10 White British nonvaccinating, and n = 9 ethnic minority vaccinating) explored parents' reasons for giving or withholding consent for HPV vaccination. Data were analysed using Framework Analysis. Results Concerns about the vaccine were raised by all nonvaccinating ethnic minority parents, and they wanted information to address these concerns. External and internal influences affected parents' decisions, as well as parents' perceptions that HPV could be prevented using means other than vaccination. Reasons were not always exclusive to nonvaccinating ethnic minority parents, although some were, including a preference for abstinence from sex before marriage. Only ethnic minority parents wanted information provided via workshops. Conclusions Ethnic differences in HPV vaccination uptake may be partly explained by concerns that were only reported by parents from some ethnic groups. Interventions to improve uptake may need to tackle difficult topics like abstinence from sex before marriage, and use a targeted format. PMID:28231418

A comparative analysis of the epidemiological impact and disease cost-savings of HPV vaccines in France.

PubMed

Bresse, Xavier; Adam, Marjorie; Largeron, Nathalie; Roze, Stephane; Marty, Rémi

2013-04-01

The aim was to compare the epidemiological and economic impact of 16/18 bivalent and 6/11/16/18 quadrivalent HPV vaccination in France, considering differences in licensed outcomes, protection against non-vaccine HPV types and prevention of HPV-6/11-related diseases. The differential impact of the two vaccines was evaluated using a published model adapted to the French setting. The target population was females aged 14-23 y and the time horizon was 100 y. A total of eight different scenarios compared vaccination impact in terms of reduction in HPV-16/18-associated carcinomas (cervical, vulvar, vaginal, anal, penile and head and neck), HPV-6/11-related genital warts and recurrent respiratory papillomatosis, and incremental reduction in cervical cancer due to potential cross-protection. Quadrivalent vaccine was associated with total discounted cost savings ranging from EUR 544-1,020 million vs. EUR 177-538 million with the bivalent vaccination (100-y time horizon). Genital wart prevention thanks to quadrivalent HPV vaccination accounted for EUR 306-380 million savings (37-56% of costs saved). In contrast, the maximal assumed cross-protection against cervical cancer resulted in EUR 13-33 million savings (4%). Prevention of vulvar, vaginal and anal cancers accounted for additional EUR 71-89 million savings (13%). In France, the quadrivalent HPV vaccination would result in significant incremental epidemiological and economic benefits vs. the bivalent vaccination, driven primarily by prevention of genital. The present analysis is the first in the French setting to consider the impact of HPV vaccination on all HPV diseases and non-vaccine types.

Correlates of Vaccine-Induced Protection against Mycobacterium tuberculosis Revealed in Comparative Analyses of Lymphocyte Populations

PubMed Central

Kurtz, Sherry L.

2015-01-01

A critical hindrance to the development of a novel vaccine against Mycobacterium tuberculosis is a lack of understanding of protective correlates of immunity and of host factors involved in a successful adaptive immune response. Studies from our group and others have used a mouse-based in vitro model system to assess correlates of protection. Here, using this coculture system and a panel of whole-cell vaccines with varied efficacy, we developed a comprehensive approach to understand correlates of protection. We compared the gene and protein expression profiles of vaccine-generated immune peripheral blood lymphocytes (PBLs) to the profiles found in immune splenocytes. PBLs not only represent a clinically relevant cell population, but comparing the expression in these populations gave insight into compartmentally specific mechanisms of protection. Additionally, we performed a direct comparison of host responses induced when immune cells were cocultured with either the vaccine strain Mycobacterium bovis BCG or virulent M. tuberculosis. These comparisons revealed host-specific and bacterium-specific factors involved in protection against virulent M. tuberculosis. Most significantly, we identified a set of 13 core molecules induced in the most protective vaccines under all of the conditions tested. Further validation of this panel of mediators as a predictor of vaccine efficacy will facilitate vaccine development, and determining how each promotes adaptive immunity will advance our understanding of antimycobacterial immune responses. PMID:26269537

Comparative cost models of a liquid nitrogen vapor phase (LNVP) cold chain-distributed cryopreserved malaria vaccine vs. a conventional vaccine

PubMed Central

Garcia, Cristina Reyes; Manzi, Fatuma; Tediosi, Fabrizio; Hoffman, Stephen L.; James, Eric R.

2013-01-01

Typically, vaccines distributed through the Expanded Program on Immunization (EPI) use a 2–8 °C cold chain with 4–5 stops. The PfSPZ Vaccine comprises whole live-attenuated cryopreserved sporozoites stored in liquid nitrogen (LN2) vapor phase (LNVP) below −140 °C and would be distributed through a LNVP cold chain. The purpose of this study was to model LNVP cold chain distribution for the cryopreserved PfSPZ Vaccine in Tanzania, estimate the costs and compare these costs to those that would be incurred in distributing a ‘conventional’ malaria vaccine through the EPI. Capital and recurrent costs for storage, transportation, labor, energy usage and facilities were determined for the birth cohort in Tanzania over five years. Costs were calculated using WHO/UNESCO calculators. These were applied to a 2–8 °C distribution model with national, regional, district, and health facility levels, and for the cryopreserved vaccine using a ‘modified hub-and-spoke’ (MH-S) LNVP distribution system comprising a central national store, peripheral health facilities and an intermediate district-level transhipment stop. Estimated costs per fully immunized child (FIC) were $ 6.11 for the LNVP-distributed cryopreserved vaccine where the LN2 is generated, and $ 6.04 with purchased LN2 (assuming US $ 1.00/L). The FIC costs for distributing a conventional vaccine using the four level 2–8 °C cold chain were $ 6.10, and with a tariff distribution system as occurs in Tanzania the FIC cost was $ 5.53. The models, therefore, predicted little difference in 5-year distribution costs between the PfSPZ Vaccine distributed through a MH-S LNVP cold chain and a conventional vaccine distributed through the more traditional EPI system. A LNVP cold chain provides additional benefits through the use of durable dry shippers because no refrigerators, freezers or refrigerated trucks are required. Thus strain at the cold chain periphery, vaccine wastage from cold chain failures and the

Comparative cost models of a liquid nitrogen vapor phase (LNVP) cold chain-distributed cryopreserved malaria vaccine vs. a conventional vaccine.

PubMed

Garcia, Cristina Reyes; Manzi, Fatuma; Tediosi, Fabrizio; Hoffman, Stephen L; James, Eric R

2013-01-02

Typically, vaccines distributed through the Expanded Program on Immunization (EPI) use a 2-8°C cold chain with 4-5 stops. The PfSPZ Vaccine comprises whole live-attenuated cryopreserved sporozoites stored in liquid nitrogen (LN(2)) vapor phase (LNVP) below -140°C and would be distributed through a LNVP cold chain. The purpose of this study was to model LNVP cold chain distribution for the cryopreserved PfSPZ Vaccine in Tanzania, estimate the costs and compare these costs to those that would be incurred in distributing a 'conventional' malaria vaccine through the EPI. Capital and recurrent costs for storage, transportation, labor, energy usage and facilities were determined for the birth cohort in Tanzania over five years. Costs were calculated using WHO/UNESCO calculators. These were applied to a 2-8°C distribution model with national, regional, district, and health facility levels, and for the cryopreserved vaccine using a 'modified hub-and-spoke' (MH-S) LNVP distribution system comprising a central national store, peripheral health facilities and an intermediate district-level transhipment stop. Estimated costs per fully immunized child (FIC) were $ 6.11 for the LNVP-distributed cryopreserved vaccine where the LN(2) is generated, and $ 6.04 with purchased LN(2) (assuming US $ 1.00/L). The FIC costs for distributing a conventional vaccine using the four level 2-8°C cold chain were $ 6.10, and with a tariff distribution system as occurs in Tanzania the FIC cost was $ 5.53. The models, therefore, predicted little difference in 5-year distribution costs between the PfSPZ Vaccine distributed through a MH-S LNVP cold chain and a conventional vaccine distributed through the more traditional EPI system. A LNVP cold chain provides additional benefits through the use of durable dry shippers because no refrigerators, freezers or refrigerated trucks are required. Thus strain at the cold chain periphery, vaccine wastage from cold chain failures and the environmental

A comparative analysis of the epidemiological impact and disease cost-savings of HPV vaccines in France

PubMed Central

Bresse, Xavier; Adam, Marjorie; Largeron, Nathalie; Roze, Stephane; Marty, Remi

2013-01-01

The aim was to compare the epidemiological and economic impact of 16/18 bivalent and 6/11/16/18 quadrivalent HPV vaccination in France, considering differences in licensed outcomes, protection against non-vaccine HPV types and prevention of HPV-6/11-related diseases. The differential impact of the two vaccines was evaluated using a published model adapted to the French setting. The target population was females aged 14–23 y and the time horizon was 100 y. A total of eight different scenarios compared vaccination impact in terms of reduction in HPV-16/18-associated carcinomas (cervical, vulvar, vaginal, anal, penile and head and neck), HPV-6/11-related genital warts and recurrent respiratory papillomatosis, and incremental reduction in cervical cancer due to potential cross-protection. Quadrivalent vaccine was associated with total discounted cost savings ranging from EUR 544–1,020 million vs. EUR 177–538 million with the bivalent vaccination (100-y time horizon). Genital wart prevention thanks to quadrivalent HPV vaccination accounted for EUR 306–380 million savings (37–56% of costs saved). In contrast, the maximal assumed cross-protection against cervical cancer resulted in EUR 13–33 million savings (4%). Prevention of vulvar, vaginal and anal cancers accounted for additional EUR 71–89 million savings (13%). In France, the quadrivalent HPV vaccination would result in significant incremental epidemiological and economic benefits vs. the bivalent vaccination, driven primarily by prevention of genital. The present analysis is the first in the French setting to consider the impact of HPV vaccination on all HPV diseases and non-vaccine types. PMID:23563511

Comparative analysis of the Rotarix™ vaccine strain and G1P[8] rotaviruses detected before and after vaccine introduction in Belgium.

PubMed

Zeller, Mark; Heylen, Elisabeth; Tamim, Sana; McAllen, John K; Kirkness, Ewen F; Akopov, Asmik; De Coster, Sarah; Van Ranst, Marc; Matthijnssens, Jelle

2017-01-01

G1P[8] rotaviruses are responsible for the majority of human rotavirus infections worldwide. The effect of universal mass vaccination with rotavirus vaccines on circulating G1P[8] rotaviruses is still poorly understood. Therefore we analyzed the complete genomes of the Rotarix™ vaccine strain, and 70 G1P[8] rotaviruses, detected between 1999 and 2010 in Belgium (36 before and 34 after vaccine introduction) to investigate the impact of rotavirus vaccine introduction on circulating G1P[8] strains. All rotaviruses possessed a complete Wa-like genotype constellation, but frequent intra-genogroup reassortments were observed as well as multiple different cluster constellations circulating in a single season. In addition, identical cluster constellations were found to circulate persistently over multiple seasons. The Rotarix™ vaccine strain possessed a unique cluster constellation that was not present in currently circulating G1P[8] strains. At the nucleotide level, the VP6, VP2 and NSP2 gene segments of Rotarix™ were relatively distantly related to any Belgian G1P[8] strain, but other gene segments of Rotarix™ were found in clusters also containing circulating Belgian strains. At the amino acid level, the genetic distance between Rotarix™ and circulating Belgian strains was considerably lower, except for NSP1. When we compared the Belgian G1P[8] strains collected before and after vaccine introduction a reduction in the proportion of strains that were found in the same cluster as the Rotarix™ vaccine strain was observed for most gene segments. The reduction in the proportion of strains belonging to the same cluster may be the result of the vaccine introduction, although natural fluctuations cannot be ruled out.

Comparative Systems Analyses Reveal Molecular Signatures of Clinically tested Vaccine Adjuvants

NASA Astrophysics Data System (ADS)

Olafsdottir, Thorunn A.; Lindqvist, Madelene; Nookaew, Intawat; Andersen, Peter; Maertzdorf, Jeroen; Persson, Josefine; Christensen, Dennis; Zhang, Yuan; Anderson, Jenna; Khoomrung, Sakda; Sen, Partho; Agger, Else Marie; Coler, Rhea; Carter, Darrick; Meinke, Andreas; Rappuoli, Rino; Kaufmann, Stefan H. E.; Reed, Steven G.; Harandi, Ali M.

2016-12-01

A better understanding of the mechanisms of action of human adjuvants could inform a rational development of next generation vaccines for human use. Here, we exploited a genome wide transcriptomics analysis combined with a systems biology approach to determine the molecular signatures induced by four clinically tested vaccine adjuvants, namely CAF01, IC31, GLA-SE and Alum in mice. We report signature molecules, pathways, gene modules and networks, which are shared by or otherwise exclusive to these clinical-grade adjuvants in whole blood and draining lymph nodes of mice. Intriguingly, co-expression analysis revealed blood gene modules highly enriched for molecules with documented roles in T follicular helper (TFH) and germinal center (GC) responses. We could show that all adjuvants enhanced, although with different magnitude and kinetics, TFH and GC B cell responses in draining lymph nodes. These results represent, to our knowledge, the first comparative systems analysis of clinically tested vaccine adjuvants that may provide new insights into the mechanisms of action of human adjuvants.

[Genetic recombination in vaccine poliovirus: comparative study in strains excreted in course of vaccination by oral poliovirus vaccine and circulating strains].

PubMed

Haddad-Boubaker, S; Ould-Mohamed-Abdallah, M V; Ben-Yahia, A; Triki, H

2010-12-01

Recombination is one of the major mechanisms of evolution in poliovirus. In this work, recombination was assessed in children during vaccination with OPV and among circulating vaccine strains isolated in Tunisia during the last 15 years in order to identify a possible role of recombination in the response to the vaccine or the acquisition of an increased transmissibility. This study included 250 poliovirus isolates: 137 vaccine isolates, excreted by children during primary vaccination with OPV and 113 isolates obtained from acute flaccid paralytic (AFP) cases and healthy contacts. Recombination was first assessed using a double PCR-RFLP, and sequencing. Nineteen per cent of recombinant strains were identified: 20% of strains excreted by vaccinees among 18% of circulating strains. The proportion of recombinant in isolates of serotype1 was very low in the two groups while the proportions of recombinants in serotypes 2 and 3 were different. In vaccinees, the frequency of recombinants in serotype3 decreased during the course of vaccination: 54% after the first dose, 32% after the second and 14% after the third dose. These results suggest that recombination enhances the ability of serotype3 vaccine strains to induce an immune response. Apart from recent vaccination, it may contribute to a more effective transmissibility of vaccine strains among human population. Copyright © 2009 Elsevier Masson SAS. All rights reserved.

Duration of protection against hepatitis A for the current two-dose vaccine compared to a three-dose vaccine schedule in children

PubMed Central

Raczniak, Gregory A.; Thomas, Timothy K.; Bulkow, Lisa R.; Negus, Susan E.; Zanis, Carolyn L.; Bruce, Michael G.; Spradling, Philip R.; Teshale, Eyasu H.; McMahon, Brian J.

2015-01-01

Background Hepatitis A is mostly a self-limiting disease but causes substantial economic burden. Consequently, United States Advisory Committee for Immunization Practices recommends inactivated hepatitis A vaccination for all children beginning at age 1 year and for high risk adults. The hepatitis A vaccine is highly effective but the duration of protection is unknown. Methods We examined the proportion of children with protective hepatitis A antibody levels (anti-HAV ≥20 mIU/mL) as well as the geometric mean concentration (GMC) of anti-HAV in a cross sectional convenience sample of individuals aged 12–24 years, who had been vaccinated with a two-dose schedule in childhood, with the initial dose at least 5 years ago. We compared a subset of data from persons vaccinated with two-doses (720 EL.U.) at age 3–6 years with a demographically similar prospective cohort that received a three-dose (360 EL.U.) schedule and have been followed for 17 years. Results No significant differences were observed when comparing GMC between the two cohorts at 10 (P = 0.467), 12 (P = 0.496), and 14 (P = 0.175) years post-immunization. For the three-dose cohort, protective antibody levels remain for 17 years and have leveled-off over the past 7 years. Conclusion The two- and three-dose schedules provide similar protection >14 years after vaccination, indicating a booster dose is not needed at this time. Plateauing anti-HAV GMC levels suggest protective antibody levels may persist long-term. PMID:23470239

A double blind, randomized, active controlled study to assess the safety, tolerability and immunogenicity of measles, mumps rubella, and varicella vaccine (MMRV) manufactured using an alternative process

PubMed Central

Marshall, Gary S.; Senders, Shelly D.; Shepard, Julie; Twiggs, Jerry D.; Gardner, Julie; Hille, Darcy; Hartzel, Jonathan; Valenzuela, Rowan; Stek, Jon E.; Helmond, Frans A.

2016-01-01

ABSTRACT Vaccination against measles, mumps, rubella, and varicella is recommended for all children in the US. Limitations manufacturing Oka/Merck strain varicella-zoster virus have hampered the availability of the combination vaccine (MMRV) against these 4 viruses, which drove the need to investigate an alternative manufacturing process. Healthy children 12-to-23 months of age at 71 US sites were randomized (1:1) to receive MMRV manufactured using an alternative process (MMRVAMP) or the currently licensed MMRV. Subjects received 2 0.5 mL doses 3 months apart. Sera were collected before and 6 weeks after Dose-1. Adverse experiences (AEs) were collected for 42 d after each dose and serious AEs and events of special interest for 180 d after Dose-2. Overall, 706 subjects were randomized to MMRVAMP and 706 to MMRV and 698 and 702 received at least 1 dose of study vaccine, respectively. The risk difference in response rates and geometric mean concentrations of antibody to measles, mumps, rubella, and varicella viruses 6 weeks after Dose-1 met non-inferiority criteria for MMRVAMP versus, MMRV. Response rates met acceptability criteria for each virus, and the seroconversion rate to varicella-zoster virus was 99.5% in both groups. Vaccine-related AEs were mostly mild-to-moderate in intensity and somewhat more common after MMRVAMP. Febrile seizures occurred at similar rates in both groups during the first 42 d after each vaccine dose. MMRVAMP is non-inferior to MMRV and represents an important advancement in maintaining an adequate supply of vaccines against these diseases. PMID:27149048

Comparative Infectivity Determinations of Dengue Virus Vaccine Candidates in Rhesus Monkeys, Mosquitoes, and Cell Cultures

DTIC Science & Technology

1993-01-28

34 are required for the evaluation of these vaccine candidates. RE: DAMDI7-89-C-9175 Page 16 REFERENCES 1. Sabin AB, Sclesinger RW, 1945. Production of...AD-A261 892 CONTRACT NO: DAMD17-89-C-9 175 \\II\\IllI\\I\\I1\\\\~il\\ TITLE: COMPARATIVE INFECTIVITY DETERMINATIONS OF DENGUE VIRUS VACCINE CANDIDATES IN... Vaccine Candidates in Rhesus Monkeys, 63002A Mosquitoes, and Cell Cultures 3M263002D870 AC 6. AUTHOR(S) DA335475 Edmundo Kraiselburd 7. PERFORMING

Comparative Effectiveness of Two Oil Adjuvant-Inactivated Avian Influenza H9N2 Vaccines.

PubMed

Kilany, Walid H; Bazid, Abdel-Hamid I; Ali, Ahmed; El-Deeb, Ayman H; El-Abideen, Mohamed A Zain; Sayed, Magdy El; El-Kady, Magdy F

2016-05-01

Low pathogenic avian influenza H9N2 virus infection has been an important risk to the Egyptian poultry industry since 2011. Economic losses have occurred from early infection and co-infection with other pathogens. Therefore, H9N2 vaccination of broiler chicks as young as 7 days old was recommended. The current inactivated H9N2 vaccines (0.5 ml/bird) administered at a reduced dose (0.25 ml/bird) do not guarantee the delivery of an effective dose for broilers. In this study, the efficacy of the reduced-dose volume (0.3 ml/bird), compared with the regular vaccine dose (0.5 ml/bird) of inactivated H9N2 vaccines using two different commercially available adjuvants, was investigated. The vaccines were prepared from the local H9N2 virus (Ck/EG/114940v/NLQP/11) using the same antigen content: 300 hemagglutinating units. Postvaccination (PV) immune response was monitored using the hemagglutination inhibition test. At 4 wk PV, both vaccinated groups were challenged using the homologous H9N2 strain at a 50% egg infective dose (EID50) of 10(6) EID50/bird via the intranasal route. Clinical signs, mortality, and virus shedding in oropharyngeal swabs were monitored at 2, 4, 6, and 10 days postchallenge (DPC). The reduced-dose volume of vaccine induced a significantly faster and higher immune response than the regular volume of vaccine at 2 and 3 wk PV. No significant difference in virus shedding between the two vaccine formulas was found (P ≥ 0.05), and both vaccines were able to stop virus shedding by 6 DPC. The reduced-dose volume of vaccine using a suitable oil adjuvant and proper antigen content can be used effectively for early immunization of broiler chicks.

Differential Adverse Event Profiles Associated with BCG as a Preventive Tuberculosis Vaccine or Therapeutic Bladder Cancer Vaccine Identified by Comparative Ontology-Based VAERS and Literature Meta-Analysis

PubMed Central

Xie, Jiangan; Codd, Christopher; Mo, Kevin; He, Yongqun

2016-01-01

M. bovis strain Bacillus Calmette–Guérin (BCG) has been the only licensed live attenuated vaccine against tuberculosis (TB) for nearly one century and has also been approved as a therapeutic vaccine for bladder cancer treatment since 1990. During its long time usage, different adverse events (AEs) have been reported. However, the AEs associated with the BCG preventive TB vaccine and therapeutic cancer vaccine have not been systematically compared. In this study, we systematically collected various BCG AE data mined from the US VAERS database and PubMed literature reports, identified statistically significant BCG-associated AEs, and ontologically classified and compared these AEs related to these two types of BCG vaccine. From 397 VAERS BCG AE case reports, we identified 64 AEs statistically significantly associated with the BCG TB vaccine and 14 AEs with the BCG cancer vaccine. Our meta-analysis of 41 peer-reviewed journal reports identified 48 AEs associated with the BCG TB vaccine and 43 AEs associated with the BCG cancer vaccine. Among all identified AEs from VAERS and literature reports, 25 AEs belong to serious AEs. The Ontology of Adverse Events (OAE)-based ontological hierarchical analysis indicated that the AEs associated with the BCG TB vaccine were enriched in immune system (e.g., lymphadenopathy and lymphadenitis), skin (e.g., skin ulceration and cyanosis), and respiratory system (e.g., cough and pneumonia); in contrast, the AEs associated with the BCG cancer vaccine mainly occurred in the urinary system (e.g., dysuria, pollakiuria, and hematuria). With these distinct AE profiles detected, this study also discovered three AEs (i.e., chills, pneumonia, and C-reactive protein increased) shared by the BCG TB vaccine and bladder cancer vaccine. Furthermore, our deep investigation of 24 BCG-associated death cases from VAERS identified the important effects of age, vaccine co-administration, and immunosuppressive status on the final BCG-associated death

Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 vaccine and HPV-6/11/16/18 vaccine

PubMed Central

Baron, Mira; Levin, Myron J; Chatterjee, Archana; Fox, Bradley; Scholar, Sofia; Rosen, Jeffrey; Chakhtoura, Nahida; Meric, Dorothée; Dessy, Francis J; Datta, Sanjoy K; Descamps, Dominique; Dubin, Gary

2011-01-01

In this observer-blind study (NCT00423046), women (N = 1,106), stratified by age (18–26, 27–35, 36–45 y), were randomized (1:1) to receive the HPV-16/18 vaccine (Cervarix®, GlaxoSmithKline Biologicals, Months 0, 1, 6) or the HPV-6/11/16/18 vaccine (Gardasil® Merck and Co., Inc., Months 0, 2, 6). Month 7 results were previously reported; we now report Month 24 results. In the according-to-protocol cohort for immunogenicity (seronegative and DNA-negative at baseline for HPV type analyzed), seropositivity rates of neutralizing antibodies (nAbs) [pseudovirion-based neutralization assay] were, across all age strata, 100% (HPV-16/18 vaccine) and 97.5–100% (HPV-6/11/16/18 vaccine) for HPV-16, and 99.0–100% (HPV-16/18 vaccine) and 72.3–84.4% (HPV-6/11/16/18 vaccine) for HPV-18. Corresponding geometric mean titers (GMTs) were 2.4–5.8-fold higher for HPV-16 and 7.7–9.4-fold higher for HPV-18 with the HPV-16/18 vaccine vs. the HPV-6/11/16/18 vaccine; HPV-16 and HPV-18 GMTs were significantly higher with the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine (p < 0.0001) in the total vaccinated cohort (received ≥1 vaccine dose, irrespective of baseline sero/DNA-status). Similar results were obtained using enzyme-linked immunosorbent assay (ELISA ). Positivity rates and GMTs of antigen-specific IgG antibodies in cervicovaginal secretions (ELISA) were not significantly different between vaccines. At Month 24, CD4+ T-cell responses for HPV-16 and HPV-18 were higher with the HPV-16/18 vaccine; memory B-cell response was higher for HPV-18 with the HPV-16/18 vaccine and similar between vaccines for HPV-16. Both vaccines were generally well tolerated. Although an immunological correlate of protection has not been defined, differences in the magnitude of immune response between vaccines may represent determinants of duration of protection. PMID:22048173

Morphodynamic evolution of Laida beach (Oka estuary, Urdaibai Biosphere Reserve, southeastern Bay of Biscay) in response to supratidal beach nourishment actions

NASA Astrophysics Data System (ADS)

Monge-Ganuzas, M.; Gainza, J.; Liria, P.; Epelde, I.; Uriarte, A.; Garnier, R.; González, M.; Nuñez, P.; Jaramillo, C.; Medina, R.

2017-12-01

Laida beach, located at the Oka estuary mouth (Urdaibai Biosphere Reserve) in the southeastern region of the Bay of Biscay, suffered the impact of a severe succession of storms during the first months of 2014. As a result of the erosion induced by these events, the beach lost its supratidal zone almost completely. The absence of a supratidal beach generated an impact on the recreational use of the beach during the summer 2014, and represented a potential impact for the coming summer 2015. Furthermore, it resulted in an overexposure and damage of adjacent infrastructures due to impinging strong waves. Therefore, the competent authorities, in coordination, decided to take action in order to nourish the supratidal zone of this beach. The solution adopted combined two different actions. The first one accomplished in spring of 2015, consisted in the mobilization of 44,800 m3 of sand from an area of 35,200 m2 equal to the 7% of the intertidal zone of Laida beach interpreted as the existing surface between the average low and high tidal limits, to the zone next to the eastern rocky beach contour. This action successfully resulted in an increase of the supratidal beach for the entire summer 2015 without negatively perturbing the morphological system. The second action was somewhat experimental and consisted in the mechanical plough of the previously existing intertidal low-amplitude ridges with the aim of increasing the sand transport toward the supratidal beach. Although this action did not lead to the increase of the supratidal beach, it seems to have resulted in an acceleration of the natural onshore migration of the bars. The objective of this contribution is to describe the morphodynamical response of the estuarine mouth after the performed actions with special emphasis on the evolution of extracted sites and the supratidal Laida beach area. The information here presented represents an innovative step in the understanding of the complex mechanisms driving the

Graphical method for comparative statistical study of vaccine potency tests.

PubMed

Pay, T W; Hingley, P J

1984-03-01

Producers and consumers are interested in some of the intrinsic characteristics of vaccine potency assays for the comparative evaluation of suitable experimental design. A graphical method is developed which represents the precision of test results, the sensitivity of such results to changes in dosage, and the relevance of the results in the way they reflect the protection afforded in the host species. The graphs can be constructed from Producer's scores and Consumer's scores on each of the scales of test score, antigen dose and probability of protection against disease. A method for calculating these scores is suggested and illustrated for single and multiple component vaccines, for tests which do or do not employ a standard reference preparation, and for tests which employ quantitative or quantal systems of scoring.

Impact of vaccine herd-protection effects in cost-effectiveness analyses of childhood vaccinations. A quantitative comparative analysis.

PubMed

Holubar, Marisa; Stavroulakis, Maria Christina; Maldonado, Yvonne; Ioannidis, John P A; Contopoulos-Ioannidis, Despina

2017-01-01

Inclusion of vaccine herd-protection effects in cost-effectiveness analyses (CEAs) can impact the CEAs-conclusions. However, empirical epidemiologic data on the size of herd-protection effects from original studies are limited. We performed a quantitative comparative analysis of the impact of herd-protection effects in CEAs for four childhood vaccinations (pneumococcal, meningococcal, rotavirus and influenza). We considered CEAs reporting incremental-cost-effectiveness-ratios (ICERs) (per quality-adjusted-life-years [QALY] gained; per life-years [LY] gained or per disability-adjusted-life-years [DALY] avoided), both with and without herd protection, while keeping all other model parameters stable. We calculated the size of the ICER-differences without vs with-herd-protection and estimated how often inclusion of herd-protection led to crossing of the cost-effectiveness threshold (of an assumed societal-willingness-to-pay) of $50,000 for more-developed countries or X3GDP/capita (WHO-threshold) for less-developed countries. We identified 35 CEA studies (20 pneumococcal, 4 meningococcal, 8 rotavirus and 3 influenza vaccines) with 99 ICER-analyses (55 per-QALY, 27 per-LY and 17 per-DALY). The median ICER-absolute differences per QALY, LY and DALY (without minus with herd-protection) were $15,620 (IQR: $877 to $48,376); $54,871 (IQR: $787 to $115,026) and $49 (IQR: $15 to $1,636) respectively. When the target-vaccination strategy was not cost-saving without herd-protection, inclusion of herd-protection always resulted in more favorable results. In CEAs that had ICERs above the cost-effectiveness threshold without herd-protection, inclusion of herd-protection led to crossing of that threshold in 45% of the cases. This impacted only CEAs for more developed countries, as all but one CEAs for less developed countries had ICERs below the WHO-cost-effectiveness threshold even without herd-protection. In several analyses, recommendation for the adoption of the target

Impact of vaccine herd-protection effects in cost-effectiveness analyses of childhood vaccinations. A quantitative comparative analysis

PubMed Central

Maldonado, Yvonne; Ioannidis, John P. A.; Contopoulos-Ioannidis, Despina

2017-01-01

Background Inclusion of vaccine herd-protection effects in cost-effectiveness analyses (CEAs) can impact the CEAs-conclusions. However, empirical epidemiologic data on the size of herd-protection effects from original studies are limited. Methods We performed a quantitative comparative analysis of the impact of herd-protection effects in CEAs for four childhood vaccinations (pneumococcal, meningococcal, rotavirus and influenza). We considered CEAs reporting incremental-cost-effectiveness-ratios (ICERs) (per quality-adjusted-life-years [QALY] gained; per life-years [LY] gained or per disability-adjusted-life-years [DALY] avoided), both with and without herd protection, while keeping all other model parameters stable. We calculated the size of the ICER-differences without vs with-herd-protection and estimated how often inclusion of herd-protection led to crossing of the cost-effectiveness threshold (of an assumed societal-willingness-to-pay) of $50,000 for more-developed countries or X3GDP/capita (WHO-threshold) for less-developed countries. Results We identified 35 CEA studies (20 pneumococcal, 4 meningococcal, 8 rotavirus and 3 influenza vaccines) with 99 ICER-analyses (55 per-QALY, 27 per-LY and 17 per-DALY). The median ICER-absolute differences per QALY, LY and DALY (without minus with herd-protection) were $15,620 (IQR: $877 to $48,376); $54,871 (IQR: $787 to $115,026) and $49 (IQR: $15 to $1,636) respectively. When the target-vaccination strategy was not cost-saving without herd-protection, inclusion of herd-protection always resulted in more favorable results. In CEAs that had ICERs above the cost-effectiveness threshold without herd-protection, inclusion of herd-protection led to crossing of that threshold in 45% of the cases. This impacted only CEAs for more developed countries, as all but one CEAs for less developed countries had ICERs below the WHO-cost-effectiveness threshold even without herd-protection. In several analyses, recommendation for the

Comparative varicella vaccine effectiveness during outbreaks in day-care centres.

PubMed

Spackova, M; Wiese-Posselt, M; Dehnert, M; Matysiak-Klose, D; Heininger, U; Siedler, A

2010-01-08

Routine varicella vaccination for children >11 months was introduced in Germany in 2004 with three different vaccine brands available. In 2008 and 2009, we investigated seven varicella outbreaks in day-care centres (DCC). Varicella disease and vaccination status of 1084 children was reviewed to evaluate vaccination coverage (VC), brand-specific varicella vaccine effectiveness (VE), and risk factors of breakthrough varicella (BV, >42 days after vaccination). A case was defined as a child with acute onset of varicella attending one of the respective DCC at the time of outbreak. Children with a previous history of varicella, age<11 months, vaccinated at age<11 months or <42 days before disease onset or during the outbreak were excluded from VE and BV risk factors analyses (adjusted for gender, age and DCC). Of 631 children with available vaccination information, 392 (62%) were vaccinated at least once. Overall VE among 352 children eligible was 71% (95% confidence interval (CI) 57-81, p<0.001) and differed significantly by disease severity and number of doses administered. Risk for BV was higher for 1 dose of Varilrix (RR=2.8, 95%CI 1.0-7.8, p=0.05) or Priorix-Tetra (RR=2.4, 95%CI 0.7-8.3, p=0.18) but lower for 2 doses of Priorix-Tetra (RR=0.5, 95%CI 0.1-2.7, p=0.41) than for 1 dose of Varivax. Enhanced efforts to increase VC in Germany and 2 doses varicella vaccine might be successful to reduce the risk for BV. The evidence that VE and risk of BV are associated with vaccine brand needs further investigation.

Cost effectiveness of pediatric pneumococcal conjugate vaccines: a comparative assessment of decision-making tools.

PubMed

Chaiyakunapruk, Nathorn; Somkrua, Ratchadaporn; Hutubessy, Raymond; Henao, Ana Maria; Hombach, Joachim; Melegaro, Alessia; Edmunds, John W; Beutels, Philippe

2011-05-12

Several decision support tools have been developed to aid policymaking regarding the adoption of pneumococcal conjugate vaccine (PCV) into national pediatric immunization programs. The lack of critical appraisal of these tools makes it difficult for decision makers to understand and choose between them. With the aim to guide policymakers on their optimal use, we compared publicly available decision-making tools in relation to their methods, influential parameters and results. The World Health Organization (WHO) requested access to several publicly available cost-effectiveness (CE) tools for PCV from both public and private provenance. All tools were critically assessed according to the WHO's guide for economic evaluations of immunization programs. Key attributes and characteristics were compared and a series of sensitivity analyses was performed to determine the main drivers of the results. The results were compared based on a standardized set of input parameters and assumptions. Three cost-effectiveness modeling tools were provided, including two cohort-based (Pan-American Health Organization (PAHO) ProVac Initiative TriVac, and PneumoADIP) and one population-based model (GlaxoSmithKline's SUPREMES). They all compared the introduction of PCV into national pediatric immunization program with no PCV use. The models were different in terms of model attributes, structure, and data requirement, but captured a similar range of diseases. Herd effects were estimated using different approaches in each model. The main driving parameters were vaccine efficacy against pneumococcal pneumonia, vaccine price, vaccine coverage, serotype coverage and disease burden. With a standardized set of input parameters developed for cohort modeling, TriVac and PneumoADIP produced similar incremental costs and health outcomes, and incremental cost-effectiveness ratios. Vaccine cost (dose price and number of doses), vaccine efficacy and epidemiology of critical endpoint (for example

Efficacy, immunogenicity, and safety evaluation of an MF59-adjuvanted quadrivalent influenza virus vaccine compared with non-adjuvanted influenza vaccine in children: a multicentre, randomised controlled, observer-blinded, phase 3 trial.

PubMed

Vesikari, Timo; Kirstein, Judith; Devota Go, Grace; Leav, Brett; Ruzycky, Mary Ellen; Isakov, Leah; de Bruijn, Marianne; Oberye, Janine; Heijnen, Esther

2018-05-01

Young children have immature immune systems and respond poorly to standard influenza vaccines. The oil-in-water emulsion adjuvant MF59 can increase antigen uptake, macrophage recruitment, lymph node migration, and avidity to influenza virus. Therefore, we aimed to assess the relative efficacy, immunogenicity, and safety of an MF59-adjuvanted, quadrivalent, inactivated (subunit) influenza vaccine (aIIV4) compared with a US-licensed non-adjuvanted influenza vaccine in children. We did a multicentre, randomised controlled, observer-blinded, phase 3 trial of 146 sites including hospitals, clinics, and clinician offices in nine countries over two influenza seasons. We included children of either sex aged 6 months through 5 years. We stratified eligible participants and randomly assigned them (1:1), using a block size of four, to receive either aIIV4 or non-adjuvanted inactivated influenza vaccine (ie, trivalent inactivated influenza vaccine [IIV3] or quadrivalent inactivated influenza vaccine [IIV4]). We masked participants, parents or guardians, and outcome assessors to the administered vaccine. Designated personnel who were not masked administered aIIV4 in both seasons, or IIV3 in season one and IIV4 in season two. All vaccinations were administered intramuscularly. Children aged 6 through 35 months received one or two 0·25 mL doses, whereas those aged 3 through 5 years received one or two doses of 0·5 mL. The number of doses was dependent on previous vaccination status: vaccine-naive participants received a total of two doses of study vaccine, the first on day 1 and the second on day 29, whereas non-naive participants received only one dose on day 1. The primary outcome was relative vaccine efficacy assessed by RT-PCR-confirmed influenza due to any influenza strain in the overall study population and in prespecified age and dose subgroups. Immunogenicity against homologous and heterologous strains of influenza and safety were also measured. This study is registered

Comparing Methods of Assessing Dog Rabies Vaccination Coverage in Rural and Urban Communities in Tanzania

PubMed Central

Sambo, Maganga; Johnson, Paul C. D.; Hotopp, Karen; Changalucha, Joel; Cleaveland, Sarah; Kazwala, Rudovick; Lembo, Tiziana; Lugelo, Ahmed; Lushasi, Kennedy; Maziku, Mathew; Mbunda, Eberhard; Mtema, Zacharia; Sikana, Lwitiko; Townsend, Sunny E.; Hampson, Katie

2017-01-01

Rabies can be eliminated by achieving comprehensive coverage of 70% of domestic dogs during annual mass vaccination campaigns. Estimates of vaccination coverage are, therefore, required to evaluate and manage mass dog vaccination programs; however, there is no specific guidance for the most accurate and efficient methods for estimating coverage in different settings. Here, we compare post-vaccination transects, school-based surveys, and household surveys across 28 districts in southeast Tanzania and Pemba island covering rural, urban, coastal and inland settings, and a range of different livelihoods and religious backgrounds. These approaches were explored in detail in a single district in northwest Tanzania (Serengeti), where their performance was compared with a complete dog population census that also recorded dog vaccination status. Post-vaccination transects involved counting marked (vaccinated) and unmarked (unvaccinated) dogs immediately after campaigns in 2,155 villages (24,721 dogs counted). School-based surveys were administered to 8,587 primary school pupils each representing a unique household, in 119 randomly selected schools approximately 2 months after campaigns. Household surveys were conducted in 160 randomly selected villages (4,488 households) in July/August 2011. Costs to implement these coverage assessments were $12.01, $66.12, and $155.70 per village for post-vaccination transects, school-based, and household surveys, respectively. Simulations were performed to assess the effect of sampling on the precision of coverage estimation. The sampling effort required to obtain reasonably precise estimates of coverage from household surveys is generally very high and probably prohibitively expensive for routine monitoring across large areas, particularly in communities with high human to dog ratios. School-based surveys partially overcame sampling constraints, however, were also costly to obtain reasonably precise estimates of coverage. Post-vaccination

A phase III clinical study to compare the immunogenicity and safety of the 9-valent and quadrivalent HPV vaccines in men.

PubMed

Van Damme, Pierre; Meijer, Chris J L M; Kieninger, Dorothee; Schuyleman, Anne; Thomas, Stephane; Luxembourg, Alain; Baudin, Martine

2016-07-29

A nine-valent human papilloma virus (9vHPV) vaccine has been developed to prevent infections and diseases related to HPV 6/11/16/18 (as per the licensed quadrivalent HPV (qHPV) vaccine) as well as to five additional oncogenic HPV types (HPV 31/33/45/52/58). The 9vHPV vaccine has the potential to prevent 90% of cervical cancers, HPV-related anal, vaginal and vulval cancers and anogenital warts. We compared the immunogenicity and safety of the 9vHPV vaccine versus the qHPV vaccine in 16-26-year-old men. Participants (N=500) were randomised to receive 9vHPV or qHPV vaccines on day 1, month 2 and month 6. Serology testing was performed on day 1 and month 7. HPV type-specific antibody titres (anti-HPV 6/11/16/18/31/33/45/52/58) were determined by competitive Luminex immunoassay and expressed as geometric mean titres and seroconversion rates. Vaccine safety was also assessed. The HPV 6/11/16/18 immune responses elicited by the 9vHPV vaccine were comparable with those elicited by the qHPV vaccine. All participants receiving the 9vHPV vaccine seroconverted for HPV 31/33/45/52/58. The 9vHPV and qHPV vaccines showed comparable safety profiles. In addition to immune responses to HPV 31/33/45/52/58, a three-dose regimen of the 9vHPV vaccine elicited a similar immune response to HPV 6/11/16/18 when compared with the qHPV vaccine in men aged 16-26years. The safety profile was also similar for the two vaccines. The results from this study support extending the efficacy findings with qHPV vaccine to 9vHPV vaccine in men aged 16-26years. NCT02114385. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Efficacy and Immunogenicity of Single-Dose AdVAV Intranasal Anthrax Vaccine Compared to Anthrax Vaccine Absorbed in an Aerosolized Spore Rabbit Challenge Model

PubMed Central

Krishnan, Vyjayanthi; Andersen, Bo H.; Shoemaker, Christine; Sivko, Gloria S.; Tordoff, Kevin P.; Stark, Gregory V.; Zhang, Jianfeng; Feng, Tsungwei; Duchars, Matthew

2015-01-01

AdVAV is a replication-deficient adenovirus type 5-vectored vaccine expressing the 83-kDa protective antigen (PA83) from Bacillus anthracis that is being developed for the prevention of disease caused by inhalation of aerosolized B. anthracis spores. A noninferiority study comparing the efficacy of AdVAV to the currently licensed Anthrax Vaccine Absorbed (AVA; BioThrax) was performed in New Zealand White rabbits using postchallenge survival as the study endpoint (20% noninferiority margin for survival). Three groups of 32 rabbits were vaccinated with a single intranasal dose of AdVAV (7.5 × 107, 1.5 × 109, or 3.5 × 1010 viral particles). Three additional groups of 32 animals received two doses of either intranasal AdVAV (3.5 × 1010 viral particles) or intramuscular AVA (diluted 1:16 or 1:64) 28 days apart. The placebo group of 16 rabbits received a single intranasal dose of AdVAV formulation buffer. All animals were challenged via the inhalation route with a targeted dose of 200 times the 50% lethal dose (LD50) of aerosolized B. anthracis Ames spores 70 days after the initial vaccination and were followed for 3 weeks. PA83 immunogenicity was evaluated by validated toxin neutralizing antibody and serum anti-PA83 IgG enzyme-linked immunosorbent assays (ELISAs). All animals in the placebo cohort died from the challenge. Three of the four AdVAV dose cohorts tested, including two single-dose cohorts, achieved statistical noninferiority relative to the AVA comparator group, with survival rates between 97% and 100%. Vaccination with AdVAV also produced antibody titers with earlier onset and greater persistence than vaccination with AVA. PMID:25673303

Comparative effects of carrier proteins on vaccine-induced immune response.

PubMed

Knuf, Markus; Kowalzik, Frank; Kieninger, Dorothee

2011-07-12

The efficacy of vaccines against major encapsulated bacterial pathogens -Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae type b (Hib) - has been significantly enhanced by conjugating the respective polysaccharides with different carrier proteins: diphtheria toxoid; non-toxic cross-reactive material of diphtheria toxin(197), tetanus toxoid, N. meningitidis outer membrane protein, and non-typeable H. influenzae-derived protein D. Hib, meningococcal, and pneumococcal conjugate vaccines have shown good safety and immunogenicity profiles regardless of the carrier protein used, although data are conflicting as to which carrier protein is the most immunogenic. Coadministration of conjugate vaccines bearing the same carrier protein has the potential for inducing either positive or negative effects on vaccine immunogenicity (immune interference). Clinical studies on the coadministration of conjugate vaccines reveal conflicting data with respect to immune interference and vaccine efficacy. Copyright © 2011 Elsevier Ltd. All rights reserved.

Comparative analysis of the Parent Attitudes about Childhood Vaccines (PACV) short scale and the five categories of vaccine acceptance identified by Gust et al.

PubMed

Oladejo, Omolade; Allen, Kristen; Amin, Avnika; Frew, Paula M; Bednarczyk, Robert A; Omer, Saad B

2016-09-22

There is a need to develop a standardized tool to aid in identifying, measuring and classifying the unique needs of vaccine-hesitant parents (VHPs). This will also assist in designing tailored interventions to address these needs. The Parental Attitude about Childhood Vaccines (PACV) short scale developed by Opel et al., and the Gust et al. vaccine acceptance categories have been acknowledged as potentially useful tools to measure parental vaccine hesitancy. The PACV short scale requires further validation. In our study, we evaluated how the Gust et al. vaccine acceptance categories correspond with the PACV short scale. As part of a larger study on vaccine attitudes, using the PACV short scale and Gust et al. vaccine acceptance categories, we assessed the correlation between the two measures using Spearman correlation coefficient, and the association between the two measures using the Cochran-Mantel-Haentszel test of association. We used logistic regression modelling to compare the association between a child's up-to-date immunization status and (a) PACV short scale and (b) Gust et al. vaccine acceptance categories. The PACV short scale and Gust et al. vaccine acceptance categories were positively correlated (r=0.6, df=198, p<0.05), and the Cochran-Mantel-Haentszel test of association yielded a statistically significant association (p<0.05). The two scales similarly predicted children's up-to-date immunization status for all recommended childhood vaccines. The ability of the PACV short scale to identify and classify parental vaccine hesitancy is similar to classification using Gust et al. vaccine acceptance categories, and both measure linear entities. The PACV short scale is recommended for screening parents at their first pediatric visit because it is easier to administer. A clearer understanding of how to classify parental vaccine hesitancy can be used to design tailored interventions based on these classifications, to address their specific needs. Copyright �

A randomized, controlled clinical trial to evaluate the immunogenicity of a PreS/S hepatitis B vaccine Sci-B-Vac™, as compared to Engerix B®, among vaccine naïve and vaccine non-responder dialysis patients.

PubMed

Elhanan, E; Boaz, M; Schwartz, I; Schwartz, D; Chernin, G; Soetendorp, H; Gal Oz, A; Agbaria, A; Weinstein, T

2018-02-01

Dialysis patients have a suboptimal response to hepatitis B (HBV) vaccination. This study aimed to compare the immunogenicity of two vaccines: the third-generation Sci-B-Vac™ vs. the second-generation Engerix B ® . The cohort included two groups of dialysis patients: naïve and previously vaccinated non-responders. Primary endpoints were antibody titers ≥10 IU/L at 3 and 7 month post-vaccination. Secondary objectives were seroprotection rates in vaccine-naïve patients and in previously vaccinated non-responders. Eighty-six patients were assigned to vaccine (Sci-B-Vac™ or Engerix B ® ) using computer-generated randomization, stratified by age, gender, diabetes, and previous HBV vaccination. Sci-B-Vac™ was administered in three doses, 10 μg, at 0, 1, and 6 months in naïve patients; or 20 μg in previously vaccinated non-responders. Engerix B ® included four doses, 40 μg at 0, 1, 2, and 6 months. Each group had 43 patients. Seroconversion was 69.8% with Engerix B ® vs. 73.2% with Sci-B-Vac™. Antibody titers at 7 months were higher with Sci-B-Vac™ (266.4 ± 383.9, median 53.4) than with Engerix ® (193.2 ± 328.9, median 19). However, these differences were not significant, perhaps due to a suboptimal sample size. This study suggests comparable immunogenicity for both vaccines. Thus, we cannot reject the null hypothesis that there is no difference in seroconversion by vaccine type. It is noteworthy that naïve patients were vaccinated with a standard dose of Sci-B-Vac™, while Engerix B ® was administered at a double dose. Similarly, although mean antibody titer levels in the Sci-B-Vac™ group were higher than in the Engerix ® group, this difference did not reach significance. Consequently, a future clinical trial should recruit a larger cohort of patients, using a standard double-dose protocol in both groups.

Immunogenicity and safety of high-dose trivalent inactivated influenza vaccine compared to standard-dose vaccine in children and young adults with cancer or HIV infection.

PubMed

Hakim, Hana; Allison, Kim J; Van de Velde, Lee-Ann; Tang, Li; Sun, Yilun; Flynn, Patricia M; McCullers, Jonathan A

2016-06-08

Approaches to improve the immune response of immunocompromised patients to influenza vaccination are needed. Children and young adults (3-21 years) with cancer or HIV infection were randomized to receive 2 doses of high-dose (HD) trivalent influenza vaccine (TIV) or of standard-dose (SD) TIV. Hemagglutination inhibition (HAI) antibody titers were measured against H1, H3, and B antigens after each dose and 9 months later. Seroconversion was defined as ≥4-fold rise in HAI titer comparing pre- and post-vaccine sera. Seroprotection was defined as a post-vaccine HAI titer ≥1:40. Reactogenicity events (RE) were solicited using a structured questionnaire 7 and 14 days after each dose of vaccine, and adverse events by medical record review for 21 days after each dose of vaccine. Eighty-five participants were enrolled in the study; 27 with leukemia, 17 with solid tumor (ST), and 41 with HIV. Recipients of HD TIV had significantly greater fold increase in HAI titers to B antigen in leukemia group and to H1 antigen in ST group compared to SD TIV recipients. This increase was not documented in HIV group. There were no differences in seroconversion or seroprotection between HD TIV and SD TIV in all groups. There was no difference in the percentage of solicited RE in recipients of HD TIV (54% after dose 1 and 38% after dose 2) compared to SD TIV (40% after dose 1 and 20% after dose 2, p=0.27 and 0.09 after dose 1 and 2, respectively). HD TIV was more immunogenic than SD TIV in children and young adults with leukemia or ST, but not with HIV. HD TIV was safe and well-tolerated in children and young adults with leukemia, ST, or HIV. Copyright © 2016 Elsevier Ltd. All rights reserved.

Efficacy and immunogenicity of single-dose AdVAV intranasal anthrax vaccine compared to anthrax vaccine absorbed in an aerosolized spore rabbit challenge model.

PubMed

Krishnan, Vyjayanthi; Andersen, Bo H; Shoemaker, Christine; Sivko, Gloria S; Tordoff, Kevin P; Stark, Gregory V; Zhang, Jianfeng; Feng, Tsungwei; Duchars, Matthew; Roberts, M Scot

2015-04-01

AdVAV is a replication-deficient adenovirus type 5-vectored vaccine expressing the 83-kDa protective antigen (PA83) from Bacillus anthracis that is being developed for the prevention of disease caused by inhalation of aerosolized B. anthracis spores. A noninferiority study comparing the efficacy of AdVAV to the currently licensed Anthrax Vaccine Absorbed (AVA; BioThrax) was performed in New Zealand White rabbits using postchallenge survival as the study endpoint (20% noninferiority margin for survival). Three groups of 32 rabbits were vaccinated with a single intranasal dose of AdVAV (7.5 × 10(7), 1.5 × 10(9), or 3.5 × 10(10) viral particles). Three additional groups of 32 animals received two doses of either intranasal AdVAV (3.5 × 10(10) viral particles) or intramuscular AVA (diluted 1:16 or 1:64) 28 days apart. The placebo group of 16 rabbits received a single intranasal dose of AdVAV formulation buffer. All animals were challenged via the inhalation route with a targeted dose of 200 times the 50% lethal dose (LD50) of aerosolized B. anthracis Ames spores 70 days after the initial vaccination and were followed for 3 weeks. PA83 immunogenicity was evaluated by validated toxin neutralizing antibody and serum anti-PA83 IgG enzyme-linked immunosorbent assays (ELISAs). All animals in the placebo cohort died from the challenge. Three of the four AdVAV dose cohorts tested, including two single-dose cohorts, achieved statistical noninferiority relative to the AVA comparator group, with survival rates between 97% and 100%. Vaccination with AdVAV also produced antibody titers with earlier onset and greater persistence than vaccination with AVA. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

A double blind, randomized, active controlled study to assess the safety, tolerability and immunogenicity of measles, mumps rubella, and varicella vaccine (MMRV) manufactured using an alternative process.

PubMed

Marshall, Gary S; Senders, Shelly D; Shepard, Julie; Twiggs, Jerry D; Gardner, Julie; Hille, Darcy; Hartzel, Jonathan; Valenzuela, Rowan; Stek, Jon E; Helmond, Frans A

2016-08-02

Vaccination against measles, mumps, rubella, and varicella is recommended for all children in the US. Limitations manufacturing Oka/Merck strain varicella-zoster virus have hampered the availability of the combination vaccine (MMRV) against these 4 viruses, which drove the need to investigate an alternative manufacturing process. Healthy children 12-to-23 months of age at 71 US sites were randomized (1:1) to receive MMRV manufactured using an alternative process (MMRV AMP ) or the currently licensed MMRV. Subjects received 2 0.5 mL doses 3 months apart. Sera were collected before and 6 weeks after Dose-1. Adverse experiences (AEs) were collected for 42 d after each dose and serious AEs and events of special interest for 180 d after Dose-2. Overall, 706 subjects were randomized to MMRV AMP and 706 to MMRV and 698 and 702 received at least 1 dose of study vaccine, respectively. The risk difference in response rates and geometric mean concentrations of antibody to measles, mumps, rubella, and varicella viruses 6 weeks after Dose-1 met non-inferiority criteria for MMRV AMP versus, MMRV. Response rates met acceptability criteria for each virus, and the seroconversion rate to varicella-zoster virus was 99.5% in both groups. Vaccine-related AEs were mostly mild-to-moderate in intensity and somewhat more common after MMRV AMP . Febrile seizures occurred at similar rates in both groups during the first 42 d after each vaccine dose. MMRV AMP is non-inferior to MMRV and represents an important advancement in maintaining an adequate supply of vaccines against these diseases.

Errant processing and structural alterations of genomes present in a varicella-zoster virus vaccine.

PubMed Central

Vlazny, D A; Hyman, R W

1985-01-01

Five minority populations of aberrant, varicella-zoster virus (VZV)-derived genomes were identified among the encapsidated DNAs obtained from the nuclear and cytoplasmic fractions of an in vitro infection initiated with a lyophilized sample of the BIKEN VZV vaccine (strain Oka). These were (i) VZV genomes, present within nuclear but not cytoplasmic viral capsids, which had been cleaved at a specific site within the short segment and which were, therefore, 3.15 megadaltons (approximately 4% of the VZV genome length) short of full length; (ii) highly deleted, repetitive VZV genomes which contained the errant cleavage site but not the usual VZV genome terminal sequences; (iii) VZV genomes into which multiples of 1 through 5 defective genome repeat units had been inserted into a homologous site; (iv) VZV genomes with additions of 0.1 or 0.18 megadaltons of DNA at both the terminal and internal ends of the short segment; and (v) VZV DNA which had lost the HindIII restriction site at map position 0.11. Images PMID:2993670

The Immunogenicity and Safety of a Combined DTaP-IPV//Hib Vaccine Compared with Individual DTaP-IPV and Hib (PRP~T) Vaccines: a Randomized Clinical Trial in South Korean Infants.

PubMed

Kang, Jin Han; Lee, Hoan Jong; Kim, Kyung Hyo; Oh, Sung Hee; Cha, Sung Ho; Lee, Jin; Kim, Nam Hee; Eun, Byung Wook; Kim, Chang Hwi; Hong, Young Jin; Kim, Hyun Hee; Lee, Kyung Yil; Kim, Yae Jean; Cho, Eun Young; Kim, Hee Soo; Guitton, Fabrice; Ortiz, Esteban

2016-09-01

Recommended infant vaccination in Korea includes DTaP-IPV and Hib vaccines administered as separate injections. In this randomized, open, controlled study we assessed the non-inferiority of immunogenicity of DTaP-IPV//Hib pentavalent combination vaccine (Pentaxim™) compared with licensed DTaP-IPV and Hib (PRP~T) vaccines. We enrolled 418 healthy Korean infants to receive either separate DTaP-IPV and Hib vaccines (n = 206) or the pentavalent DTaP-IPV//Hib (n = 208) vaccine at 2, 4, 6 months of age. Antibodies to all components were measured before the first vaccination and one month after the third, and safety was assessed after each vaccination including recording of reactions by parents. We confirmed the non-inferiority of DTaP-IPV//Hib compared with DTaP-IPV and Hib vaccines; 100% of both groups achieved seroprotection against D, T, IPV and PRP~T, and 97.5%-99.0% demonstrated seroresponses to pertussis antigens. Antibody levels were similar in both groups, except for those to the Hib component, PRP~T. In separate and combined groups geometric mean concentrations of anti-PRP~T antibodies were 23.9 and 11.0 μg/mL, respectively, but 98.3% and 97.4% had titers ≥ 1 μg/mL, indicative of long-term protection. All vaccines were well tolerated, with no vaccine-related serious adverse event. Both groups had similar safety profiles, but the combined vaccine group had fewer injection site reactions. The immunological non-inferiority and similar safety profile of DTaP-IPV//Hib vaccine to separate DTaP-IPV and Hib vaccines, with the advantage of fewer injections and injection site reactions, supports the licensure and incorporation of DTaP-IPV//Hib into the Korean national vaccination schedule (Clinical trial registry, NCT01214889).

Comparative safety and efficacy of subcutaneous and intradermal administration of inactivated Japanese encephalitis vaccine during predeployment preparations in the Australian Defence Force.

PubMed

Kitchener, Scott; Nasveld, Peter; Brennan, Len; Ward, David

2006-12-01

Japanese encephalitis is a viral disease emerging in areas of influence for the Australian Defence Force immediately north of the continent, including the Torres Strait border of Australia and Papua, New Guinea. Only the mouse brain-derived, inactivated, Nakayama strain vaccine is commercially available to the Australian Defence Force. This vaccine has a high cost and significant adverse event profile, requiring restricted duties after administration. To address these issues, intradermal vaccination (either single intradermal administration or two intradermal injections at two separate sites) was assessed, compared with the conventional subcutaneous vaccination method, in a randomized controlled trial among soldiers preparing for deployment. Dual intradermal vaccination (0.1 mL at two sites) was found to have a slightly more favorable adverse event profile while maintaining comparable serological efficacy and reduced cost. An expansion of the concept and a test of logistics were conducted by vaccinating a battalion formation during predeployment medical preparations. The method of vaccination was well accepted and retained comparable immunogenicity.

Identification of vaccinia virus epitope-specific HLA-A*0201-restricted T cells and comparative analysis of smallpox vaccines

PubMed Central

Drexler, Ingo; Staib, Caroline; Kastenmüller, Wolfgang; Stevanović, Stefan; Schmidt, Burkhard; Lemonnier, François A.; Rammensee, Hans-Georg; Busch, Dirk H.; Bernhard, Helga; Erfle, Volker; Sutter, Gerd

2003-01-01

Despite worldwide eradication of naturally occurring variola virus, smallpox remains a potential threat to both civilian and military populations. New, safe smallpox vaccines are being developed, and there is an urgent need for methods to evaluate vaccine efficacy after immunization. Here we report the identification of an immunodominant HLA-A*0201-restricted epitope that is recognized by cytotoxic CD8+ T cells and conserved among Orthopoxvirus species including variola virus. This finding has permitted analysis and monitoring of epitope-specific T cell responses after immunization and demonstration of the identified T cell specificity in an A*0201-positive human donor. Vaccination of transgenic mice allowed us to compare the immunogenicity of several vaccinia viruses including highly attenuated, replication-deficient modified vaccinia virus Ankara (MVA). MVA vaccines elicited levels of CD8+ T cell responses that were comparable to those induced by the replication-competent vaccinia virus strains. Finally, we demonstrate that MVA vaccination is fully protective against a lethal respiratory challenge with virulent vaccinia virus strain Western Reserve. Our data provide a basis to rationally estimate immunogenicity of safe, second-generation poxvirus vaccines and suggest that MVA may be a suitable candidate. PMID:12518065

Recombination of Globally Circulating Varicella-Zoster Virus

PubMed Central

Depledge, Daniel P.; Kundu, Samit; Atkinson, Claire; Brown, Julianne; Haque, Tanzina; Hussaini, Yusuf; MacMahon, Eithne; Molyneaux, Pamela; Papaevangelou, Vassiliki; Sengupta, Nitu; Koay, Evelyn S. C.; Tang, Julian W.; Underhill, Gillian S.; Grahn, Anna; Studahl, Marie; Breuer, Judith; Bergström, Tomas

2015-01-01

ABSTRACT Varicella-zoster virus (VZV) is a human herpesvirus, which during primary infection typically causes varicella (chicken pox) and establishes lifelong latency in sensory and autonomic ganglia. Later in life, the virus may reactivate to cause herpes zoster (HZ; also known as shingles). To prevent these diseases, a live-attenuated heterogeneous vaccine preparation, vOka, is used routinely in many countries worldwide. Recent studies of another alphaherpesvirus, infectious laryngotracheitis virus, demonstrate that live-attenuated vaccine strains can recombine in vivo, creating virulent progeny. These findings raised concerns about using attenuated herpesvirus vaccines under conditions that favor recombination. To investigate whether VZV may undergo recombination, which is a prerequisite for VZV vaccination to create such conditions, we here analyzed 115 complete VZV genomes. Our results demonstrate that recombination occurs frequently for VZV. It thus seems that VZV is fully capable of recombination if given the opportunity, which may have important implications for continued VZV vaccination. Although no interclade vaccine-wild-type recombinant strains were found, intraclade recombinants were frequently detected in clade 2, which harbors the vaccine strains, suggesting that the vaccine strains have already been involved in recombination events, either in vivo or in vitro during passages in cell culture. Finally, previous partial and complete genomic studies have described strains that do not cluster phylogenetically to any of the five established clades. The additional VZV strains sequenced here, in combination with those previously published, have enabled us to formally define a novel sixth VZV clade. IMPORTANCE Although genetic recombination has been demonstrated to frequently occur for other human alphaherpesviruses, herpes simplex viruses 1 and 2, only a few ancient and isolated recent recombination events have hitherto been demonstrated for VZV. In the

Post Approval Human Papillomavirus Vaccine Uptake Is Higher in Minorities Compared to Whites in Girls Presenting for Well-Child Care.

PubMed

Pierce, Jennifer Young; Korte, Jeffrey E; Carr, Laura A; Gasper, Catherine B; Modesitt, Susan C

2013-07-17

Since introduction of the human papillomavirus (HPV) vaccine, there remains low uptake compared to other adolescent vaccines. There is limited information postapproval about parental attitudes and barriers when presenting for routine care. This study evaluates HPV vaccine uptake and assesses demographics and attitudes correlating with vaccination for girls aged 11-12 years. A prospective cohort study was performed utilizing the University of Virginia (UVA) Clinical Data Repository (CDR). The CDR was used to identify girls aged 11-12 presenting to any UVA practice for a well-child visit between May 2008 and April 2009. Billing data were searched to determine rates of HPV vaccine uptake. The parents of all identified girls were contacted four to seven months after the visit to complete a telephone questionnaire including insurance information, child's vaccination status, HPV vaccine attitudes, and demographics. Five hundred and fifty girls were identified, 48.2% of whom received at least one HPV vaccine dose. White race and private insurance were negatively associated with HPV vaccine initiation (RR 0.72, 95% CI 0.61-0.85 and RR 0.85, 95% CI 0.72-1.01, respectively). In the follow-up questionnaire, 242 interviews were conducted and included in the final cohort. In the sample, 183 (75.6%) parents reported white race, 38 (15.7%) black race, and 27 (11.2%) reported other race. Overall 85% of parents understood that the HPV vaccine was recommended and 58.9% of parents believed the HPV vaccine was safe. In multivariate logistic regression, patients of black and other minority races were 4.9 and 4.2 times more likely to receive the HPV vaccine compared to their white counterparts. Safety concerns were the strongest barrier to vaccination. To conclude, HPV vaccine uptake was higher among minority girls and girls with public insurance in this cohort.

Immunogenicity and safety results from a randomized multicenter trial comparing a Tdap-IPV vaccine (REPEVAX®) and a tetanus monovalent vaccine in healthy adults

PubMed Central

Laurichesse, Henri; Zimmermann, Ulrich; Galtier, Florence; Launay, Odile; Duval, Xavier; Richard, Patrick; Sadorge, Christine; Soubeyrand, Benoit

2012-01-01

In adults with a tetanus-prone injury, combined vaccines such as Tdap-IPV (REPEVAX®) can boost immunity against several diseases simultaneously. This Phase IIIb, parallel-group, open-label trial compared antibody responses to Tdap-IPV and tetanus monovalent vaccine (TMV; Vaccin Tétanique Pasteur® or Tetavax®) against tetanus toxoid 10 and 28 d post-vaccination. Between July and December 2009, four centers in France and five in Germany recruited healthy adults who had received a tetanus-containing vaccine 5−10 y previously. Participants were randomized 1:1 to receive at the first visit a single dose (0.5 mL) of Tdap-IPV or TMV, with follow-up visits at Day 10 and Day 28. Outcomes: per protocol (PP) population immunogenicity at Day 10 (primary) and at Day 28 (secondary); safety throughout the study. Of 456 adults randomized, 223 received Tdap-IPV and 233 received TMV (PP population: 183 and 199 participants, respectively). All participants receiving Tdap-IPV and 99.0% receiving TMV had an anti-tetanus antibody concentration ≥ 0.1 IU/mL, confirming non-inferiority of Tdap-IPV to TMV (95% confidence interval of the difference: –1.2, 3.6). Number of adverse events reported was comparable in each group. Injection-site reactions were reported by 76.6% participants receiving Tdap-IPV and 74.6% receiving TMV. Systemic events (e.g., malaise, myalgia and headache) were reported in 47.7% and 39.7% of the Tdap-IPV and the TMV groups, respectively. Tdap-IPV is effective and well-tolerated for use in the management of tetanus-prone injuries in emergency settings in persons for whom a booster against diphtheria, pertussis and poliomyelitis is also needed. ClinicalTrials.gov identifier: NCT00928785. Research sponsored by Sanofi Pasteur MSD. PMID:23032160

Comparing human papillomavirus vaccine knowledge and intentions among parents of boys and girls

PubMed Central

Lindley, Megan C.; Jeyarajah, Jenny; Yankey, David; Curtis, C. Robinette; Markowitz, Lauri E.; Stokley, Shannon

2016-01-01

ABSTRACT Background/Objective: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. Previous research suggests some differences between male and female adolescents in correlates of vaccine receipt and reasons for non-vaccination; few studies examine both sexes together. This analysis assessed knowledge and attitudes related to HPV disease and vaccination, intention to vaccinate, and reasons for delayed vaccination or non-vaccination among parents of boys and girls 13–17 y old in 50 states, the District of Columbia, and selected local areas. Methods: National Immunization Survey-Teen 2013 data were analyzed and gender differences examined. Results: In this sample, adolescent boys were more likely than girls to be unvaccinated and less likely to have completed the HPV vaccination series (p < 0.005 for both). Parents of girls were more likely than parents of boys to report a provider recommendation for HPV vaccination (65.0% vs. 42.1%). Only 29% of girls' parents reported a provider recommendation to begin vaccination by 11–12 y old. Among unvaccinated teens, parental intention to vaccinate in the next 12 months did not differ by sex, but reasons for vaccination or non-vaccination did. Many parents do not know the recommended number of HPV doses. Conclusions: Gender differences in provider vaccination recommendations and reasons for vaccination might partially explain differential HPV uptake by male and female adolescents. Clinicians should offer strong recommendations for HPV vaccination at 11–12 y old for both girls and boys. To reduce missed opportunities, HPV vaccination should be presented in the context of, and given concurrently with, other routinely administered vaccines. PMID:27003108

Vaccination Strategies: a comparative study in an epidemic scenario

NASA Astrophysics Data System (ADS)

Prates, D. B.; Jardim, C. L. T. F.; Ferreira, L. A. F.; da Silva, J. M.; Kritz, M. V.

2016-08-01

Epidemics are an extremely important matter of study within the Mathematical Modeling area and can be widely found in the literature. Some epidemiological models use differential equations, which are very sensible to parameters, to represent and describe the diseases mathematically. For this work, a variation of the SIR model is discussed and applied to a certain epidemic scenario, wherein vaccination is introduced through two different strategies: constant vaccination and vaccination in pulses. Other epidemiological and population aspects are also considered, such as mortality/natality and infection rates. The analysis and results are performed through numerical solutions of the model and a special attention is given to the discussion generated by the paramenters variation.

Immunogenicity and safety of a quadrivalent inactivated influenza virus vaccine compared with a comparator quadrivalent inactivated influenza vaccine in a pediatric population: A phase 3, randomized noninferiority study.

PubMed

Airey, Jolanta; Albano, Frank R; Sawlwin, Daphne C; Jones, Alison Graves; Formica, Neil; Matassa, Vince; Leong, Jane

2017-05-09

Seqirus 2010 Southern Hemisphere split-virion trivalent inactivated influenza vaccine (IIV3) was associated with increased febrile reactions in children. Studies in vitro concluded that increasing concentrations of splitting agent decreased residual lipids and attenuated proinflammatory cytokine signals associated with fever. We assessed immunogenicity and safety of a quadrivalent inactivated influenza vaccine (IIV4; produced using higher concentration of splitting agent) versus a United States-licensed comparator IIV4 in healthy children aged 5-17years. Participants (N=2278) were randomized 3:1 and stratified by age (5-8years; 9-17years) to receive IIV4 (n=1709) or comparator IIV4 (n=569). Primary objective was to demonstrate noninferiority of IIV4 versus comparator IIV4 as assessed by hemagglutination inhibition (HI) geometric mean titer (GMT) ratio (upper bound of two-sided 95% confidence interval [CI]≤1.5) and difference in seroconversion rate (upper bound of two-sided 95% CI≤10%) for all four vaccine strains. HI antibody titers were assessed at baseline and 28days postvaccination. Solicited and unsolicited adverse events were assessed during each 7- and 28-day postvaccination period, respectively. IIV4 met immunogenicity criteria for noninferiority. Adjusted GMT ratios (comparator IIV4/IIV4) for A/H1N1, A/H3N2, B/Yamagata, and B/Victoria strains were 1.01 (95% CI; 0.93, 1.09), 1.05 (0.96, 1.15), 0.89 (0.81, 0.98), and 0.92 (0.83, 1.02), respectively. Corresponding values for differences (95% CI) in seroconversion rates (comparator IIV4 minus IIV4) were -3.1 (-8.0, 1.8), 0.4 (-4.5, 5.3), -3.4 (-8.3, 1.5), and -2.0 (-6.9, 2.9). Fever rates were numerically higher, but not statistically different, with IIV4 versus comparator IIV4. No new safety signals were reported. IIV4 demonstrated immunological noninferiority to the comparator IIV4 with a clinically acceptable safety profile in children aged 5-17years. Increased levels of virus splitting agent seem to

Intralesional Mycobacterium w Vaccine Versus Cryotherapy in Treatment of Refractory Extragenital Warts: A Randomized, Open-Label, Comparative Study.

PubMed

Dhakar, Ashok K; Dogra, Sunil; Vinay, Keshavamurthy; Sarangal, Rishu; Kanwar, Amrinder J; Singh, Mini P

2016-01-01

Initial reports of immunotherapy using intralesional Mycobacterium w (Mw) vaccine have documented its useful role in treatment of genital and extragenital warts. To compare the efficacy and safety of intralesional Mw vaccine versus cryotherapy in the treatment of refractory extragenital warts. This was a prospective, randomized, comparative study of 66 patients. The outcome was assessed in terms of complete clearance of warts and change in Dermatology Life Quality Index (DLQI) score. Complete clearance of treated warts was seen in 66.7% (20/30) and 65.5% (19/29) of patients in the Mw and cryotherapy groups, respectively (P = .769). Clearance of distant warts was significantly (P = .004) high in the Mw group. Improvement in DLQI was greater in the Mw group. Both treatment modalities were well tolerated, and no major side effects occurred. Mw vaccine and cryotherapy are equally efficacious in treatment of refractory extragenital warts. Mw vaccine has an added advantage of clearance of distant warts. © The Author(s) 2015.

Vaccines for preventing rotavirus diarrhoea: vaccines in use.

PubMed

Soares-Weiser, Karla; Maclehose, Harriet; Ben-Aharon, Irit; Goldberg, Elad; Pitan, Femi; Cunliffe, Nigel

2010-05-12

Rotavirus results in higher diarrhoea-related death in children less than five years of age than any other single agent, particularly in low- and middle-income countries. The World Health Organization has recommended the use of rotavirus vaccines in childhood immunization schedules. To evaluate rotavirus vaccines approved for use (Rotarix, RotaTeq, and Lanzhou Lamb Rotavirus (LLR)) for preventing rotavirus diarrhoea. In February 2010, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (published in The Cochrane Library 2009, Issue 1), MEDLINE, EMBASE, LILACS, and BIOSIS. We also searched the ICTRP (January 2010) and checked reference lists of identified studies. Randomized controlled trials comparing rotavirus vaccines approved for use with placebo, no intervention, or another vaccine in children. Two authors independently assessed trial eligibility, extracted data, and assessed risk of bias. Dichotomous data were combined using the risk ratio (RR) and 95% confidence intervals (CI). Thirty-four trials that included 175,944 participants met the inclusion criteria. They evaluated Rotarix (26 trials; 99,841 participants) and RotaTeq (eight trials; 76,103 participants), and had variable risk of bias (where information provided). None of the identified trials used LLR or compared rotavirus vaccines. Compared to placebo, Rotarix and RotaTeq were both effective at reducing rotavirus diarrhoea (severe cases and cases of any severity). They also reduced all-cause diarrhoea (severe cases), and hospitalizations and need for medical attention caused by rotavirus diarrhoea. However, few data were available for Rotarix and all-cause diarrhoea. Versus the placebo groups, participants in each vaccine group had similar numbers of deaths, serious adverse events, reactogenicity profiles (fever, diarrhoea, and vomiting), and adverse events that required discontinuation of the vaccination schedule. Both vaccines were immunogenic (measured by virus shedding

Comparative Efficacy of Feline Leukemia Virus (FeLV) Inactivated Whole-Virus Vaccine and Canarypox Virus-Vectored Vaccine during Virulent FeLV Challenge and Immunosuppression.

PubMed

Patel, M; Carritt, K; Lane, J; Jayappa, H; Stahl, M; Bourgeois, M

2015-07-01

Four vaccines for feline leukemia virus (FeLV) are available in the United States. This study's purpose was to compare the efficacy of Nobivac feline 2-FeLV (an inactivated, adjuvanted whole-virus vaccine) and PureVax recombinant FeLV (a live, canarypox virus-vectored vaccine) following FeLV challenge. Cats were vaccinated at 9 and 12 weeks with Nobivac feline 2-FeLV (group A, n = 11) or PureVax recombinant FeLV (group B, n = 10). Group C (n = 11) comprised unvaccinated controls. At 3 months postvaccination, cats were immunosuppressed and challenged with FeLV-A/61E. The outcomes measured were persistent antigenemia at 12 weeks postchallenge (PC) and proviral DNA and viral RNA at 3 to 9 weeks PC. Persistent antigenemia was observed in 0 of 11 cats in group A, 5 of 10 cats in group B, and 10 of 11 cats in group C. Group A was significantly protected compared to those in groups B (P < 0.013) and C (P < 0.0001). No difference was found between groups B and C (P > 0.063). The preventable fraction was 100% for group A and 45% for group B. At 9 weeks PC, proviral DNA and viral RNA were detected 1 of 11 cats in group A, 6 of 10 cats in group B, and 9 of 11 cats in group C. Nucleic acid loads were significantly lower in group A than in group C (P < 0.01). Group A had significantly lower proviral DNA loads than group B at weeks 6 to 9 (P < 0.02). The viral RNA loads were significantly lower in group A than in group B at weeks 7 to 9 (P < 0.01). The results demonstrate that Nobivac feline 2-FeLV-vaccinated cats were fully protected against persistent antigenemia and had significantly smaller amounts of proviral DNA and plasma viral RNA loads than PureVax recombinant FeLV-vaccinated cats and unvaccinated controls. Copyright © 2015, Patel et al.

Comparative trial of the canine parvovirus, canine distemper virus and canine adenovirus type 2 fractions of two commercially available modified live vaccines.

PubMed

Bergman, J G H E; Muniz, M; Sutton, D; Fensome, R; Ling, F; Paul, G

2006-11-25

The results of vaccinating two groups of puppies with commercial vaccines, both of which claimed to provide adequate protection with a final vaccination at 10 weeks of age, were compared. Groups of 19 and 20 puppies with similar titres of maternally derived antibodies against canine parvovirus (cpv), canine distemper virus (cdv) and canine adenovirus type 2 (cav-2) at four weeks of age were vaccinated at six and 10 weeks of age and their responses to each vaccination were measured by comparing the titres against cpv, cdv and cav-2 in the serum samples taken immediately before the vaccination and four weeks later. After the vaccination at six weeks of age, all 19 of the puppies in group 1 had responded to cpv and cdv, and 14 had responded to cav-2; in group 2, 17 of the 20 had responded to cpv, 19 to cdv and 15 to cav-2. In both groups the puppies that did not respond to the first vaccination had responded serologically to cpv, cdv and cav-2 at 10 weeks of age.

Comparative evaluation of techniques for the manufacturing of dendritic cell-based cancer vaccines

PubMed Central

Dohnal, Alexander Michael; Graffi, Sebastian; Witt, Volker; Eichstill, Christina; Wagner, Dagmar; Ul-Haq, Sidrah; Wimmer, Doris; Felzmann, Thomas

2009-01-01

Abstract Manufacturing procedures for cellular therapies are continuously improved with particular emphasis on product safety. We previously developed a dendritic cell (DC) cancer vaccine technology platform that uses clinical grade lipopolysaccharide (LPS) and interferon (IFN)-y for the maturation of monocyte derived DCs. DCs are frozen after 6 hrs exposure at a semi-mature stage (smDCs) retaining the capacity to secret interleukin (IL)-12 and thus support cytolytic T-cell responses, which is lost at full maturation. We compared closed systems for monocyte enrichment from leucocyte apheresis products from healthy individuals using plastic adherence, CD14 selection, or CD2/19 depletion with magnetic beads, or counter flow centrifugation (elutriation) using a clinical grade in comparison to a research grade culture medium for the following DC generation. We found that elutriation was superior compared to the other methods showing 36 ± 4% recovery, which was approximately 5-fold higher as the most frequently used adherence protocol (8 ± 1%), and a very good purity (92 ± 5%) of smDCs. Immune phenotype and IL-12 secretion (adherence: 1.4 ± 0.4; selection: 20 ± 0.6; depletion: 1 ±0.5; elutriation: 3.6 ± 1.5 ng/ml) as well as the potency of all DCs to stimulate T cells in an allogeneic mixed leucocyte reaction did not show statistically significant differences. Research grade and clinical grade DC culture media were equally potent and freezing did not impair the functions of smDCs. Finally, we assessed the functional capacity of DC cancer vaccines manufactured for three patients using this optimized procedure thereby demonstrating the feasibility of manufacturing DC cancer vaccines that secret IL-12 (9.4 ± 6.4 ng/ml). We conclude that significant steps were taken here towards clinical grade DC cancer vaccine manufacturing. PMID:18363835

Comparative efficacy of intranasal and injectable vaccines in stimulating Bordetella bronchiseptica-reactive anamnestic antibody responses in household dogs

PubMed Central

Ellis, John A.; Gow, Sheryl P.; Lee, Lindsey B.; Lacoste, Stacey; Ball, Eileen C.

2017-01-01

In order to determine the comparative efficacy of injectable and intranasal vaccines to stimulate Bordetella bronchiseptica (Bb)-reactive anamnestic antibodies, a trial was conducted using 144 adult household dogs of various breeds and ages, which had been previously administered intranasal Bb vaccine approximately 12 months before enrollment. Dogs were randomized into 2 groups and blood, nasal swabs, and pharyngeal swabs were collected prior to the administration of single component Bb vaccines intranasally or parenterally. Ten to 14 days later all dogs were resampled to measure changes in systemic and local antibody to Bb. There were no differences in the changes in Bb-reactive serum IgG and nasal IgA between the groups, whereas intranasally vaccinated dogs had significantly higher Bb-reactive serum IgA. These data indicate that both of the current generation of intranasal (modified-live) and injectable (acellular) Bb vaccines can stimulate anamnestic local and systemic antibody responses in previously vaccinated, Bb-seropositive adult household dogs. PMID:28761185

Vaccine decision-making begins in pregnancy: Correlation between vaccine concerns, intentions and maternal vaccination with subsequent childhood vaccine uptake.

PubMed

Danchin, M H; Costa-Pinto, J; Attwell, K; Willaby, H; Wiley, K; Hoq, M; Leask, J; Perrett, K P; O'Keefe, Jacinta; Giles, M L; Marshall, H

2017-08-12

Maternal and childhood vaccine decision-making begins prenatally. Amongst pregnant Australian women we aimed to ascertain vaccine information received, maternal immunisation uptake and attitudes and concerns regarding childhood vaccination. We also aimed to determine any correlation between a) intentions and concerns regarding childhood vaccination, (b) concerns about pregnancy vaccination, (c) socioeconomic status (SES) and (d) uptake of influenza and pertussis vaccines during pregnancy and routine vaccines during childhood. Women attending public antenatal clinics were recruited in three Australian states. Surveys were completed on iPads. Follow-up phone surveys were done three to six months post delivery, and infant vaccination status obtained via the Australian Childhood Immunisation Register (ACIR). Between October 2015 and March 2016, 975 (82%) of 1184 mothers consented and 406 (42%) agreed to a follow up survey, post delivery. First-time mothers (445; 49%) had significantly more vaccine concerns in pregnancy and only 73% had made a decision about childhood vaccination compared to 89% of mothers with existing children (p-value<0.001). 66% of mothers reported receiving enough information during pregnancy on childhood vaccination. In the post delivery survey, 46% and 82% of mothers reported receiving pregnancy influenza and pertussis vaccines respectively. The mother's degree of vaccine hesitancy and two attitudinal factors were correlated with vaccine uptake post delivery. There was no association between reported maternal vaccine uptake or SES and childhood vaccine uptake. First time mothers are more vaccine hesitant and undecided about childhood vaccination, and only two thirds of all mothers believed they received enough information during pregnancy. New interventions to improve both education and communication on childhood and maternal vaccines, delivered by midwives and obstetricians in the Australian public hospital system, may reduce vaccine hesitancy

A comparative evaluation of a novel vaccine in APP/PS1 mouse models of Alzheimer's disease.

PubMed

Carrera, Iván; Etcheverría, Ignacio; Fernández-Novoa, Lucía; Lombardi, Valter Ruggero Maria; Lakshmana, Madepalli Krishnappa; Cacabelos, Ramón; Vigo, Carmen

2015-01-01

Immunization against amyloid-beta-peptide (Aβ) has been widely investigated as a potential immunotherapeutic approach for Alzheimer's disease (AD). With the aim of developing an active immunogenic vaccine without need of coadjuvant modification for human trials and therefore avoiding such side effects, we designed the Aβ 1-42 vaccine (EB101), delivered in a liposomal matrix, that based on our previous studies significantly prevents and reverses the AD neuropathology, clearing Aβ plaques while markedly reducing neuronal degeneration, behavioral deficits, and minimizing neuroinflammation in APP/PS1 transgenic mice. Here, the efficacy of our immunogenic vaccine EB101 was compared with the original immunization vaccine cocktail Aβ 42 + CFA/IFA (Freund's adjuvant), in order to characterize the effect of sphingosine-1-phosphate (S1P) in the immunotherapeutic response. Quantitative analysis of amyloid burden showed a notable decrease in the neuroinflammation reaction against Aβ plaques when S1P was compared with other treatments, suggesting that S1P plays a key role as a neuroprotective agent. Moreover, EB101 immunized mice presented a protective immunogenic reaction resulting in the increase of Aβ-specific antibody response and decrease of reactive glia in the affected brain areas, leading to a Th2 immunological reaction.

Comparative safety, immunogenicity, and efficacy of several anti‐H5N1 influenza experimental vaccines in a mouse and chicken models (Testing of killed and live H5 vaccine)

PubMed Central

Gambaryan, Alexandra S.; Lomakina, Natalia F.; Boravleva, Elizaveta Y.; Kropotkina, Ekaterina A.; Mashin, Vadim V.; Krasilnikov, Igor V.; Klimov, Alexander I.; Rudenko, Larisa G.

2011-01-01

Please cite this paper as: Gambaryan et al. (2011) Comparative safety, immunogenicity, and efficacy of several anti‐H5N1 influenza experimental vaccines in a mouse and chicken models. Parallel testing of killed and live H5 vaccine. Influenza and Other Respiratory Viruses 6(3), 188–195. Objective  Parallel testing of inactivated (split and whole virion) and live vaccine was conducted to compare the immunogenicity and protective efficacy against homologous and heterosubtypic challenge by H5N1 highly pathogenic avian influenza virus. Method  Four experimental live vaccines based on two H5N1 influenza virus strains were tested; two of them had hemagglutinin (HA) of A/Vietnam/1203/04 strain lacking the polybasic HA cleavage site, and two others had hemagglutinins from attenuated H5N1 virus A/Chicken/Kurgan/3/05, with amino acid substitutions of Asp54/Asn and Lys222/Thr in HA1 and Val48/Ile and Lys131/Thr in HA2 while maintaining the polybasic HA cleavage site. The neuraminidase and non‐glycoprotein genes of the experimental live vaccines were from H2N2 cold‐adapted master strain A/Leningrad/134/17/57 (VN‐Len and Ku‐Len) or from the apathogenic H6N2 virus A/Gull/Moscow/3100/2006 (VN‐Gull and Ku‐Gull). Inactivated H5N1 and H1N1 and live H1N1 vaccine were used for comparison. All vaccines were applied in a single dose. Safety, immunogenicity, and protectivity against the challenge with HPAI H5N1 virus A/Chicken/Kurgan/3/05 were estimated. Results  All experimental live H5 vaccines tested were apathogenic as determined by weight loss and conferred more than 90% protection against lethal challenge with A/Chicken/Kurgan/3/05 infection. Inactivated H1N1 vaccine in mice offered no protection against challenge with H5N1 virus, while live cold‐adapted H1N1 vaccine reduced the mortality near to zero level. Conclusions  The high yield, safety, and protectivity of VN‐Len and Ku‐Len made them promising strains for the production of inactivated and live

Enhanced efficacy and reduced toxicity of multifactorial adjuvants compared with unitary adjuvants as cancer vaccines.

PubMed

Ahonen, Cory L; Wasiuk, Anna; Fuse, Shinichiro; Turk, Mary Jo; Ernstoff, Marc S; Suriawinata, Arief A; Gorham, James D; Kedl, Ross M; Usherwood, Edward J; Noelle, Randolph J

2008-03-15

Identification of Toll-like receptors (TLRs) and their ligands, and tumor necrosis factor-tumor necrosis factor receptor (TNF-TNFR) pairs have provided the first logical, hypothesis-based strategies to molecularly concoct adjuvants to elicit potent cell-mediated immunity via activation of innate and adaptive immunity. However, isolated activation of one immune pathway in the absence of others can be toxic, ineffective, and detrimental to long-term, protective immunity. Effective engineered vaccines must include agents that trigger multiple immunologic pathways. Here, we report that combinatorial use of CD40 and TLR agonists as a cancer vaccine, compared with monotherapy, elicits high frequencies of self-reactive CD8(+) T cells, potent tumor-specific CD8(+) memory, CD8(+) T cells that efficiently infiltrate the tumor-burdened target organ; therapeutic efficacy; heightened ratios of CD8(+) T cells to FoxP3(+) cells at the tumor site; and reduced hepatotoxicity. These findings provide intelligent strategies for the formulation of multifactorial vaccines to achieve maximal efficacy in cancer vaccine trials in humans.

Monitoring heavy metal concentrations in the sediments of the Moskva and Oka River system- Results of the Volga-Rhine-Project

NASA Astrophysics Data System (ADS)

Andresen, Höpke

2010-05-01

In the course of the Volga-Rhine-Project sediment, water and pore water samples were collected on the Volga as well as the Moskva and Oka river systems. The sampling area discussed here is located south east of the city of Moscow. Sediment samples were taken along the Moskva River between Moscow and the city of Kolomna, which is approximately 100 km to the southeast of Moscow and in the Oka River close to the confluence with the Moskva River (Kolomna). The first sampling campaign in this region took place in 1993, followed by further sampling in 1997 and 2007. For evaluation of sediment quality classification systems are often used. The geo-accumulation index proposed by Mueller (1979) is a classification system which consists of seven classes given by the following expression: I = log2×Cn- geo 1.5×Bn Where Cn = measured concentration; Bn = background value (Turekian & Wedepol 1961) of element n and 1.5 = background matrix correction factor. The geo-accumulation index consists of seven grades (0-6) which indicate the enrichment of an element compared to the background value. These grades range from 'not polluted' to 'very strongly polluted'. Another possibility to express sediment contamination is to evaluate the effects on the ecosystem. The lowest effect level (LEL) gives the concentrations of the heavy metals in sediment below which no effect on the majority of the sediment dwelling organisms is expected. The probable effect level (PEL) represents the concentration of heavy metals above which the organisms frequently will show adverse effects. Both of these approaches were used to evaluate the results of the Volga-Rhine-Project. In the last two decades the concentrations of heavy metals in the sediments decreased by up to 60%. In 1993 sediments revealed high concentrations of several heavy metals such as chromium, cadmium, lead, zinc, arsenic, nickel and cobalt, whereas in 2007 only two sediment samples were classified as 'very strongly polluted' regarding

Comparative analysis of pentavalent rotavirus vaccine strains and G8 rotaviruses identified during vaccine trial in Africa.

PubMed

Heylen, Elisabeth; Zeller, Mark; Ciarlet, Max; Lawrence, Jody; Steele, Duncan; Van Ranst, Marc; Matthijnssens, Jelle

2015-10-06

RotaTeqTM is a pentavalent rotavirus vaccine based on a bovine rotavirus genetic backbone in vitro reassorted with human outer capsid genes. During clinical trials of RotaTeqTM in Sub-Saharan Africa, the vaccine efficacy over a 2-year follow-up was lower against the genotypes contained in the vaccine than against the heterotypic G8P[6] and G8P[1] rotavirus strains of which the former is highly prevalent in Africa. Complete genome analyses of 43 complete rotavirus genomes collected during phase III clinical trials of RotaTeqTM in Sub-Saharan Africa, were conducted to gain insight into the high level of cross-protection afforded by RotaTeqTM against these G8 strains. Phylogenetic analysis revealed the presence of a high number of bovine rotavirus gene segments in these human G8 strains. In addition, we performed an in depth analysis on the individual amino acid level which showed that G8 rotaviruses were more similar to the RotaTeqTM vaccine than non-G8 strains. Because RotaTeqTM possesses a bovine genetic backbone, the high vaccine efficacy against G8 strains might be partially explained by the fact that all these strains contain a complete or partial bovine-like backbone. Altogether, this study supports the hypothesis that gene segments other than VP7 and VP4 play a role in vaccine-induced immunity.

Randomized comparative study of the serum antihemagglutinin and antineuraminidase antibody responses to six licensed trivalent influenza vaccines.

PubMed

Couch, Robert B; Atmar, Robert L; Keitel, Wendy A; Quarles, John M; Wells, Janet; Arden, Nancy; Niño, Diane

2012-12-17

and frequencies were low for the N1 of A/H1N1 virus. Trivalent inactivated influenza vaccines with similar HA dosage induce similar serum anti-HA antibody responses in healthy adults. Current inactivated vaccines all induce serum anti-NA antibody to the N1 and N2 NA proteins but some are better than others for N1 or N2. The live vaccine, Flumist, was a poor inducer of either anti-HA or anti-NA serum antibody compared to inactivated vaccine in the healthy adults. In view of the capacity for contributing to immunity to influenza in humans, developing guidelines for NA content and induction of NA antibody is desirable. Copyright © 2012 Elsevier Ltd. All rights reserved.

Beliefs about Vaccinations: Comparing a Sample from a Medical School to That from the General Population

PubMed Central

Latella, Lauren E.; McAuley, Robert J.; Rabinowitz, Mitchell

2018-01-01

The current study compares health care professionals’ beliefs about vaccination statements with the beliefs of a sample of individuals from the general population. Students and faculty within a medical school (n = 58) and a sample from the general population in the United States (n = 177) were surveyed regarding their beliefs about vaccinations. Participants evaluated statements about vaccinations (both supporting and opposing), and indicated whether they thought the general population would agree with them. Overall, it was found that subjects in both populations agreed with statements supporting vaccination over opposing statements, but the general population was more likely to categorize the supporting statements as beliefs rather than facts. Additionally, there was little consensus within each population as to which statements were considered facts versus beliefs. Both groups underestimated the number of people that would agree with them; however, the medical affiliates showed the effect significantly more. Implications for medical education and health communication are discussed. PMID:29597319

Equine neonates have attenuated humoral and cell-mediated immune responses to a killed adjuvanted vaccine compared to adult horses.

PubMed

Ryan, Clare; Giguère, Steeve

2010-12-01

The objectives of this study were to compare relative vaccine-specific serum immunoglobulin concentrations, vaccine-specific lymphoproliferative responses, and cytokine profiles of proliferating lymphocytes between 3-day-old foals, 3-month-old foals, and adult horses after vaccination with a killed adjuvanted vaccine. Horses were vaccinated intramuscularly twice at 3-week intervals with a vaccine containing antigens from bovine viral respiratory pathogens to avoid interference from maternal antibody. Both groups of foals and adult horses responded to the vaccine with a significant increase in vaccine-specific IgGa and IgG(T) concentrations. In contrast, only adult horses and 3-month-old foals mounted significant vaccine-specific total IgG, IgGb, and IgM responses. Vaccine-specific concentrations of IgM and IgG(T) were significantly different between all groups, with the highest concentrations occurring in adult horses, followed by 3-month-old foals and, finally, 3-day-old foals. Only the adult horses mounted significant vaccine-specific lymphoproliferative responses. Baseline gamma interferon (IFN-γ) and interleukin-4 (IL-4) concentrations were significantly lower in 3-day-old foals than in adult horses. Vaccination resulted in a significant decrease in IFN-γ concentrations in adult horses and a significant decrease in IL-4 concentrations in 3-day-old foals. After vaccination, the ratio of IFN-γ/IL-4 in both groups of foals was significantly higher than that in adult horses. The results of this study indicate that the humoral and lymphoproliferative immune responses to this killed adjuvanted vaccine are modest in newborn foals. Although immune responses improve with age, 3-month-old foals do not respond with the same magnitude as adult horses.

Bovine neonatal pancytopenia--comparative proteomic characterization of two BVD vaccines and the producer cell surface proteome (MDBK).

PubMed

Euler, Kerstin N; Hauck, Stefanie M; Ueffing, Marius; Deeg, Cornelia A

2013-01-23

Bovine neonatal pancytopenia (BNP) is a disease syndrome in newborn calves of up to four weeks of age, first observed in southern Germany in 2006. By now, cases have been reported in several countries around the globe. Many affected calves die within days due to multiple haemorrhages, thrombocytopenia, leukocytopenia and bone marrow depletion. A certain vaccine directed against Bovine Virus Diarrhoea Virus (BVDV) was recently shown to be associated with BNP pathogenesis. Immunized cows develop alloantibodies that are transferred to newborn calves via colostrum intake. In order to further elucidate BNP pathogenesis, the purpose of this study was to characterize and compare the protein composition of the associated vaccine to another vaccine directed against BVDV not related to BNP and the cell surface proteome of MDBK (Madin-Darby Bovine Kidney) cells, the cell line used for production of the associated vaccine. By SDS-PAGE and mass spectrometry, we were able to detect several coagulation-related and immune modulatory proteins, as well as cellular and serum derived molecules being shared between the associated vaccine and MDBK cells. Furthermore, the number of proteins identified in the BNP related vaccine was almost as high as the number of surface proteins detected on MDBK cells and exceeded the amount of proteins identified in the non-BNP related vaccine over 3.5 fold. The great amount of shared cellular and serum derived proteins confirm that the BNP associated vaccine contained many molecules originating from MDBK cells and vaccine production. The respective vaccine was not purified enough to prevent the development of alloantibodies. To narrow down possible candidate proteins, those most likely to represent a trigger for BNP pathogenesis are presented in this study, giving a fundament for further analysis in future research.

Predicting human papillomavirus vaccine uptake in young adult women: Comparing the Health Belief Model and Theory of Planned Behavior

PubMed Central

Gerend, Mary A.; Shepherd, Janet E.

2012-01-01

Background Although theories of health behavior have guided thousands of studies, relatively few studies have compared these theories against one another. Purpose The purpose of the current study was to compare two classic theories of health behavior—the Health Belief Model (HBM) and the Theory of Planned Behavior (TPB)—in their prediction of human papillomavirus (HPV) vaccination. Methods After watching a gain-framed, loss-framed, or control video, women (N=739) ages 18–26 completed a survey assessing HBM and TPB constructs. HPV vaccine uptake was assessed ten months later. Results Although the message framing intervention had no effect on vaccine uptake, support was observed for both the TPB and HBM. Nevertheless, the TPB consistently outperformed the HBM. Key predictors of uptake included subjective norms, self-efficacy, and vaccine cost. Conclusions Despite the observed advantage of the TPB, findings revealed considerable overlap between the two theories and highlighted the importance of proximal versus distal predictors of health behavior. PMID:22547155

Vaccinating my way--use of alternative vaccination schedules in New York State.

PubMed

Nadeau, Jessica A; Bednarczyk, Robert A; Masawi, Munyaradzi R; Meldrum, Megan D; Santilli, Loretta; Zansky, Shelley M; Blog, Debra S; Birkhead, Guthrie S; McNutt, Louise-Anne

2015-01-01

To identify children vaccinated following an alternative vaccine schedule using immunization information system data and determine the impact of alternative schedule use on vaccine coverage. Children born in New York State, outside New York City, between January 1, 2009 and August 14, 2011 were assessed for vaccination patterns consistent with use of an alternative schedule. Children who by 9 months of age had at least 3 vaccination visits recorded in the statewide mandatory immunization information system after 41 days of age were classified as either attempting to conform to the Centers for Disease Control and Prevention published recommended vaccination schedule or an alternative schedule. The number of vaccination visits and up-to-date status at age 9 months were compared between groups. Of the 222 628 children studied, the proportion of children following an alternative schedule was 25%. These children were significantly less likely to be up-to-date at age 9 months (15%) compared with those conforming to the routine schedule (90%, P < .05). Children following an alternative schedule on average had about 2 extra vaccine visits compared with children following a routine schedule (P < .05). Almost 1 in 4 children in this study appear to be intentionally deviating from the routine schedule. Intentional deviation leads to poor vaccination coverage leaving children vulnerable to infection and increasing the potential for vaccine-preventable disease outbreaks. Copyright © 2015 Elsevier Inc. All rights reserved.

Trivalent MDCK cell culture-derived influenza vaccine Optaflu (Novartis Vaccines).

PubMed

Doroshenko, Alexander; Halperin, Scott A

2009-06-01

Annual influenza epidemics continue to have a considerable impact in both developed and developing countries. Vaccination remains the principal measure to prevent seasonal influenza and reduce associated morbidity and mortality. The WHO recommends using established mammalian cell culture lines as an alternative to egg-based substrates in the manufacture of influenza vaccine. In June 2007, the EMEA approved Optaflu, a Madin Darby canine kidney cell culture-derived influenza vaccine manufactured by Novartis Vaccines. This review examines the advantages and disadvantages of cell culture-based technology for influenza vaccine production, compares immunogenicity and safety data for Optaflu with that of currently marketed conventional egg-based influenza vaccines, and considers the prospects for wider use of cell culture-based influenza vaccines.

A clinical trial of WRL 105 strain live attenuated influenza vaccine comparing four methods of intranasal vaccination.

PubMed Central

Freestone, D. S.; Bowker, C. H.; Letley, E.; Ferris, R. D.; White, W. G.; Barnes, G. M.

1976-01-01

A single intranasal dose of 10(7-0) EID50 recombinant WRL 105 strain live attenuated influenza vaccine was administered intranasally to 193 volunteers either as nose drops or by one of three spray devices which produced sprays of differing physical characteristics. In volunteers with homologous haemagglutinating inhibiting antibody titres of less than or equal to 20 before vaccination, seroconversion rates varied widely from 80% following the administration of drops to 71%, 57% and 28% with the three spray devices. In the week following vaccination 16 (22%) of 74 volunteers who were found to show a fourfold or greater antibody response to took analgesics to control symptoms in comparison with 4 (7%) of 58 volunteers who exhibited no serological response to vaccination (P less than 0-05). However, neither the occurrence of upper respiratory nor systemic symptoms were significantly different in these two groups and the degree of attenuation of the recombinant WRL 105 strain appears to be acceptable for future use. PMID:1064672

Medicaid-based child restraint system disbursement and education and the vaccines for children program: comparative cost-effectiveness.

PubMed

Goldstein, Jesse A; Winston, Flaura K; Kallan, Michael J; Branas, Charles C; Schwartz, J Sanford

2008-01-01

Low-income children are disproportionately at risk for preventable motor-vehicle injury. Many of these children are covered by Medicaid programs placing substantial economic burden on states. Child restraint systems (CRSs) have demonstrated efficacy in preventing death and injury among children in crashes but remain underutilized because of poor access and education. The objective of this study was to evaluate the cost-effectiveness of Medicaid-based reimbursement for CRS disbursement and education for low-income children and compare it with vaccinations covered under the Vaccines For Children (VFC) program. A cost-effectiveness analysis was performed of Medicaid reimbursement for CRS disbursement/education for low-income children based on data from public and private databases. Primary outcomes measured include cost per life-year saved, death, serious injury, and minor injury averted, as well as medical, parental work loss, and future productivity loss costs averted. Cost-effectiveness calculations were compared with published cost-effectiveness data for vaccinations covered under the VFC program. The adoption of a CRS disbursement/education program could prevent up to 2 deaths, 12 serious injuries, and 51 minor injuries per 100,000 low-income children annually. When fully implemented, the program could save Medicaid over $1 million per 100,000 children in direct medical costs while costing $13 per child per year after all 8 years of benefit. From the perspective of Medicaid, the program would cost $17,000 per life-year saved, $60,000 per serious injury prevented, and $560,000 per death averted. The program would be cost saving from a societal perspective. These data are similar to published vaccination cost-effectiveness data. Implementation of a Medicaid-funded CRS disbursement/education program was comparable in cost-effectiveness with federal vaccination programs targeted toward similar populations and represents an important potential strategy for addressing

Comparing human papillomavirus vaccine concerns on Twitter: a cross-sectional study of users in Australia, Canada and the UK

PubMed Central

Shapiro, Gilla K; Surian, Didi; Dunn, Adam G; Perry, Ryan; Kelaher, Margaret

2017-01-01

Objective Opposition to human papillomavirus (HPV) vaccination is common on social media and has the potential to impact vaccine coverage. This study aims to conduct an international comparison of the proportions of tweets about HPV vaccines that express concerns, the types of concerns expressed and the social connections among users posting about HPV vaccines in Australia, Canada and the UK. Design Using a cross-sectional design, an international comparison of English language tweets about HPV vaccines and social connections among Twitter users posting about HPV vaccines between January 2014 and April 2016 was conducted. The Health Belief Model, one of the most widely used theories in health psychology, was used as the basis for coding the types of HPV vaccine concerns expressed on Twitter. Setting The content of tweets and the social connections between users who posted tweets about HPV vaccines from Australia, Canada and the UK. Population 16 789 Twitter users who posted 43 852 tweets about HPV vaccines. Main outcome measures The proportions of tweets expressing concern, the type of concern expressed and the proportions of local and international social connections between users. Results Tweets expressing concerns about HPV vaccines made up 14.9% of tweets in Canada, 19.4% in Australia and 22.6% in the UK. The types of concerns expressed were similar across the three countries, with concerns related to ‘perceived barriers’ being the most common. Users expressing concerns about HPV vaccines in each of the three countries had a relatively high proportion of international followers also expressing concerns. Conclusions The proportions and types of HPV vaccine concerns expressed on Twitter were similar across the three countries. Twitter users who mostly expressed concerns about HPV vaccines were better connected to international users who shared their concerns compared with users who did not express concerns about HPV vaccines. PMID:28982821

Comparative effectiveness of different strategies of oral cholera vaccination in bangladesh: a modeling study.

PubMed

Dimitrov, Dobromir T; Troeger, Christopher; Halloran, M Elizabeth; Longini, Ira M; Chao, Dennis L

2014-12-01

Killed, oral cholera vaccines have proven safe and effective, and several large-scale mass cholera vaccination efforts have demonstrated the feasibility of widespread deployment. This study uses a mathematical model of cholera transmission in Bangladesh to examine the effectiveness of potential vaccination strategies. We developed an age-structured mathematical model of cholera transmission and calibrated it to reproduce the dynamics of cholera in Matlab, Bangladesh. We used the model to predict the effectiveness of different cholera vaccination strategies over a period of 20 years. We explored vaccination programs that targeted one of three increasingly focused age groups (the entire vaccine-eligible population of age one year and older, children of ages 1 to 14 years, or preschoolers of ages 1 to 4 years) and that could occur either as campaigns recurring every five years or as continuous ongoing vaccination efforts. Our modeling results suggest that vaccinating 70% of the population would avert 90% of cholera cases in the first year but that campaign and continuous vaccination strategies differ in effectiveness over 20 years. Maintaining 70% coverage of the population would be sufficient to prevent sustained transmission of endemic cholera in Matlab, while vaccinating periodically every five years is less effective. Selectively vaccinating children 1-14 years old would prevent the most cholera cases per vaccine administered in both campaign and continuous strategies. We conclude that continuous mass vaccination would be more effective against endemic cholera than periodic campaigns. Vaccinating children averts more cases per dose than vaccinating all age groups, although vaccinating only children is unlikely to control endemic cholera in Bangladesh. Careful consideration must be made before generalizing these results to other regions.

A population based study comparing changes in rotavirus burden on the Island of Ireland between a highly vaccinated population and an unvaccinated population.

PubMed

Armstrong, Gillian; Gallagher, Naomh; Cabrey, Paul; Graham, Adele M; McKeown, Paul J; Jackson, Sarah; Dallat, Mary; Smithson, Richard D

2016-09-07

Rotavirus infection is a leading cause of gastroenteritis in infants and children globally. Reductions in rotavirus activity have been observed following introduction of rotavirus vaccination programmes, however a reductions have also been reported in some unvaccinated countries. The Island of Ireland incorporates the two jurisdictions Northern Ireland (NI) and the Republic of Ireland (IE). Both have similarities in climate, demography, morbidity and mortality but distinct health administrations and vaccination policies. Rotarix was added to the childhood immunisation programme in NI on the 1 July 2013. IE have not introduced routine rotavirus vaccination to date. The aim of this population based ecological study was to evaluate the impact of the rotavirus vaccine on burden of rotavirus disease in NI, and to compare with IE as an unvaccinated control population. This will help determine if the changes seen were due to the rotavirus vaccine, or due to confounding factors. A number of population based measures of disease burden were compared in both jurisdictions pre-vaccine (six years; 2007/08-2012/13) and post-vaccine (two years; 2013/14-2014/15). The data sources included national rotavirus surveillance data based on laboratory reports/notifications; hospital admission data; and notifications of gastroenteritis in under 2year olds. In the post-vaccination period, rotavirus incidence in NI dropped by 54% while in IE it increased by 19% compared to the pre-vaccine period. Notifications of gastroenteritis in under 2s in NI declined by 53% and hospital admissions in under 5year olds in NI declined by 40% in the post vaccine period. This natural experiment demonstrated a significant reduction in rotavirus disease activity post-vaccine introduction in NI with associated reductions in healthcare utilisation, with a concurrent increase in rotavirus disease activity in the non-vaccinated population in IE. These findings support rotavirus vaccination as an effective measure

Comparative analysis of the immune responses induced by native versus recombinant versions of the ASP-based vaccine against the bovine intestinal parasite Cooperia oncophora.

PubMed

González-Hernández, Ana; Borloo, Jimmy; Peelaers, Iris; Casaert, Stijn; Leclercq, Georges; Claerebout, Edwin; Geldhof, Peter

2018-01-01

The protective capacities of a native double-domain activation-associated secreted protein (ndd-ASP)-based vaccine against the cattle intestinal nematode Cooperia oncophora has previously been demonstrated. However, protection analysis upon vaccination with a recombinantly produced antigen has never been performed. Therefore, the aim of the current study was to test the protective potential of a Pichia-produced double-domain ASP (pdd-ASP)-based vaccine against C. oncophora. Additionally, we aimed to compare the cellular and humoral mechanisms underlying the vaccine-induced responses by the native (ndd-ASP) and recombinant vaccines. Immunisation of cattle with the native C. oncophora vaccine conferred significant levels of protection after an experimental challenge infection, whereas the recombinant vaccine did not. Moreover, vaccination with ndd-ASP resulted in a higher proliferation of CD4-T cells both systemically and in the small intestinal mucosa when compared with animals vaccinated with the recombinant antigen. In terms of humoral response, although both native and recombinant vaccines induced similar levels of antibodies, animals vaccinated with the native vaccine were able to raise antibodies with greater specificity towards ndd-ASP in comparison with antibodies raised by vaccination with the recombinant vaccine, suggesting a differential immune recognition towards the ndd-ASP and pdd-ASP. Finally, the observation that animals displaying antibodies with higher percentages of recognition towards ndd-ASP also exhibited the lowest egg counts suggests a potential relationship between antibody specificity and protection. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Comparative evaluation of non-structural protein-antibody detecting ELISAs for foot-and-mouth disease sero-surveillance under intensive vaccination.

PubMed

Sharma, Gaurav Kumar; Mohapatra, Jajati Keshari; Mahajan, Sonalika; Matura, Rakesh; Subramaniam, Saravanan; Pattnaik, Bramhadev

2014-10-01

Foot-and-mouth disease is a highly infectious and contagious disease of livestock animals with transboundary and economical importance. Animals in the endemic settings are regularly vaccinated in addition to intensive surveillance for control of the disease. Under intensive vaccination, detection of infected animals among the vaccinated population is essential to monitor the infection and to track down the virus movement. Sero-surveillance and retrospective disease diagnosis is performed primarily by detecting antibodies against non-structural proteins (NSPs) of FMD virus which are usually absent in the inactivated vaccine formulations. The study was conducted with an objective to compare simultaneously performance of six NSP ELISAs in detecting infected animals in the areas covered under intensive vaccination, and to assess their fit-for-purpose attribute for sero-surveillance of FMD in India. A panel of bovine serum samples consisting of samples collected from infected with FMDV, vaccinated and naive animals were constituted. In addition, samples collected at random from areas having varied FMD situation and vaccination coverage were tested simultaneously by the six NSP ELISAs to compare their performances. The four indigenous assays showed varying degrees of correlation with the two commercial kits. The study validated that, in all the groups of samples, the indigenous assays were equally sensitive and specific as the two commercial kits. Among all the six assays, PrioCheck and in-house 3ABC I-ELISAs showed maximum sensitivity for detection of infected animals, whereas 3AB3 I-ELISA and 3ABC C-ELISA showed maximum specificity. The study concluded that the in-house available assays are equally capable as the commercially available kits for differentiation of infected animals under intensive vaccination and identifies the 3AB3 I-ELISA with optimum sensitivity and specificity for the purpose of sero-surveillance in India. Copyright © 2014 Elsevier B.V. All rights

A public-professional web-bridge for vaccines and vaccination: user concerns about vaccine safety.

PubMed

García-Basteiro, Alberto L; Alvarez-Pasquín, María-José; Mena, Guillermo; Llupià, Anna; Aldea, Marta; Sequera, Victor-Guillermo; Sanz, Sergi; Tuells, Jose; Navarro-Alonso, José-Antonio; de Arísteguí, Javier; Bayas, José-María

2012-05-28

Vacunas.org (http://www.vacunas.org), a website founded by the Spanish Association of Vaccinology offers a personalized service called Ask the Expert, which answers any questions posed by the public or health professionals about vaccines and vaccination. The aim of this study was to analyze the factors associated with questions on vaccination safety and determine the characteristics of questioners and the type of question asked during the period 2008-2010. A total of 1341 questions were finally included in the analysis. Of those, 30% were related to vaccine safety. Questions about pregnant women had 5.01 higher odds of asking about safety (95% CI 2.82-8.93) than people not belonging to any risk group. Older questioners (>50 years) were less likely to ask about vaccine safety compared to younger questioners (OR: 0.44, 95% CI 0.25-0.76). Questions made after vaccination or related to influenza (including H1N1) or travel vaccines were also associated with a higher likelihood of asking about vaccine safety. These results identify risk groups (pregnant women), population groups (older people) and some vaccines (travel and influenza vaccines, including H1N1) where greater efforts to provide improved, more-tailored vaccine information in general and on the Internet are required. Copyright © 2011 Elsevier Ltd. All rights reserved.

Comparative Effectiveness of Different Strategies of Oral Cholera Vaccination in Bangladesh: A Modeling Study

PubMed Central

Dimitrov, Dobromir T.; Troeger, Christopher; Halloran, M. Elizabeth; Longini, Ira M.; Chao, Dennis L.

2014-01-01

Background Killed, oral cholera vaccines have proven safe and effective, and several large-scale mass cholera vaccination efforts have demonstrated the feasibility of widespread deployment. This study uses a mathematical model of cholera transmission in Bangladesh to examine the effectiveness of potential vaccination strategies. Methods & Findings We developed an age-structured mathematical model of cholera transmission and calibrated it to reproduce the dynamics of cholera in Matlab, Bangladesh. We used the model to predict the effectiveness of different cholera vaccination strategies over a period of 20 years. We explored vaccination programs that targeted one of three increasingly focused age groups (the entire vaccine-eligible population of age one year and older, children of ages 1 to 14 years, or preschoolers of ages 1 to 4 years) and that could occur either as campaigns recurring every five years or as continuous ongoing vaccination efforts. Our modeling results suggest that vaccinating 70% of the population would avert 90% of cholera cases in the first year but that campaign and continuous vaccination strategies differ in effectiveness over 20 years. Maintaining 70% coverage of the population would be sufficient to prevent sustained transmission of endemic cholera in Matlab, while vaccinating periodically every five years is less effective. Selectively vaccinating children 1–14 years old would prevent the most cholera cases per vaccine administered in both campaign and continuous strategies. Conclusions We conclude that continuous mass vaccination would be more effective against endemic cholera than periodic campaigns. Vaccinating children averts more cases per dose than vaccinating all age groups, although vaccinating only children is unlikely to control endemic cholera in Bangladesh. Careful consideration must be made before generalizing these results to other regions. PMID:25473851

Primary vaccine failure to routine vaccines: Why and what to do?

PubMed

Wiedermann, Ursula; Garner-Spitzer, Erika; Wagner, Angelika

2016-01-01

There are 2 major factors responsible for vaccine failures, the first is vaccine-related such as failures in vaccine attenuation, vaccination regimes or administration. The other is host-related, of which host genetics, immune status, age, health or nutritional status can be associated with primary or secondary vaccine failures. The first describes the inability to respond to primary vaccination, the latter is characterized by a loss of protection after initial effectiveness. Our studies concentrate on the evaluation of immunological characteristics responsible for primary vaccine failures in different (risk) populations for which the underlying mechanisms are currently unknown. Here we summarise current knowledge and findings from our studies. About 2-10% of healthy individuals fail to mount antibody levels to routine vaccines. Comparing the immune responses to different vaccines in non-responder and high-responder vaccinees revealed that hypo-responsiveness is antigen/vaccine-specific at the humoral but not at the cellular level. We found that T-regulatory as well as B-regulatory cells and the production of IL-10 are involved in non/hypo-responsiveness. Non-responsiveness increases with age and in particular vaccination to a novel vaccine in persons > 65 years is associated with a high low/non-responder rate, indicating that vaccine schedules and doses (at least for primary vaccination) should be adapted according to age. In light of the growing number of allergic but also obese people, our current studies concentrate on these risk groups to reveal whether different vaccination approaches are necessary for optimal protection compared to healthy individuals. These studies are in line with the significant paradigm shift taking place in many fields of medical research and care, and will extend the concept of personalised medicine into the field of vaccinology.

Additive benefits of pneumococcal and influenza vaccines among elderly persons aged 75 years or older in Taiwan--a representative population-based comparative study.

PubMed

Chang, Yu-Chia; Chou, Yiing-Jenq; Liu, Jen-Yin; Yeh, Te-Feng; Huang, Nicole

2012-09-01

It remains unclear whether pneumococcal vaccine provides additional protection to the elderly who have already vaccinated with influenza vaccine. This retrospective cohort study aimed to assess the additive effect of pneumococcal and influenza vaccines on the risk of mortality, hospitalization, and inpatient expenditure in the elderly aged 75 years or older in Taiwan. Data were extracted from the National Health Insurance claims data of a nationally representative elderly sample. To reduce potential selection bias, we employed a propensity score matching method to classify the vaccination status into 3 groups. Multivariable logistic and linear regression models were used to compare the outcomes among different groups. Each group contained 8142 subjects. The results indicated that an additive effect of receiving both vaccines was associated with a significantly lower all-cause mortality (relative risk [RR]: 0.74; 95% confidence interval [CI]: 0.57-0.96), hospitalization of all diseases including pneumonia, influenza, chronic obstructive pulmonary disease, respiratory diseases, and congestive heart disease (RR: 0.77; 95% CI: 0.67-0.90), and a 13% reduction (95% CI: 0.81-0.94) in inpatient expenditures of all diseases when compared with receiving influenza vaccine alone. This study confirmed that vaccination of elderly individuals with pneumococcal vaccine and influenza vaccine concomitantly has substantial beneficial effects. Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Comparative evaluation of the potential impact of rotavirus versus HPV vaccination in GAVI-eligible countries: a preliminary analysis focused on the relative disease burden.

PubMed

Kim, Sun-Young; Sweet, Steven; Chang, Joshua; Goldie, Sue J

2011-06-16

Immunization policymakers at global and local levels need to establish priorities among new vaccines competing for limited resources. However, comparison of the potential impact of single vaccination programs is challenging, primarily due to the limited number of vaccine analyses as well as their differing analytic approaches and reporting formats. The purpose of this study is to provide early insight into how the comparative impact of different new vaccines could be assessed in resource-poor settings with respect to affordability, cost-effectiveness, and distributional equity. We compared the health, economic, and financial consequences of introducing the two vaccines in 72 GAVI-eligible countries using a number of different outcome measures to evaluate affordability, cost-effectiveness, and distributional equity. We use simple static models to standardize the analytic framework and improve comparability between the two new vaccines. These simple models were validated by leveraging previously developed, more complex models for rotavirus and human papillomavirus (HPV). With 70% coverage of a single-age cohort of infants and pre-adolescent girls, the lives saved with rotavirus (~274,000) and HPV vaccines (~286,000) are similar, although the timing of averted mortality differs; rotavirus-attributable deaths occur in close proximity to infection, while HPV-related cancer deaths occur largely after age 30. Deaths averted per 1000 vaccinated are 5.2 (rotavirus) and 12.6 (HPV). Disability-adjusted life years (DALYs) averted were ~7.15 million (rotavirus) and ~1.30 million (HPV), reflecting the greater influence of discounting on the latter, given the lagtime between vaccination and averted cancer. In most countries (68 for rotavirus and 66 for HPV, at the cost of I$25 per vaccinated individual) the incremental cost per DALY averted was lower than each country's GDP per capita. Financial resources required for vaccination with rotavirus are higher than with HPV since both

Comparative cost-effectiveness of HPV vaccines in the prevention of cervical cancer in Malaysia.

PubMed

Ezat, Sharifa W P; Aljunid, Syed

2010-01-01

Cervical cancer (CC) had the second highest incidence of female cancers in Malaysia in 2003-2006. Prevention is possible by both Pap smear screening and HPV vaccination with either the bivalent vaccine (BV) or the quadrivalent vaccine (QV). In the present study, cost effectiveness options were compared for three programs i.e. screening via Pap smear; modeling of HPV vaccination (QV and BV) and combined strategy (screening plus vaccination). A scenario based sensitivity analysis was conducted using screening population coverages (40-80%) and costs of vaccines (RM 100-200/dose) were calculated. This was an economic burden, cross sectional study in 2006-2009 of respondents interviewed from six public Gynecology-Oncology hospitals. Methods included expert panel discussions to estimate treatment costs of CC, genital warts and vulva/vagina cancers by severity and direct interviews with respondents using costing and SF-36 quality of life questionnaires. A total of 502 cervical cancer patients participated with a mean age at 53.3±11.2 years and a mean marriage length of 27.7±12.1 years, Malays accounting for 44.2%. Cost/quality adjusted life year (QALY) for Pap smear in the base case was RM 1,215 and RM 1,100 at increased screening coverage. With QV only, in base case it was RM 15,662 and RM 24,203 when the vaccination price was increased. With BV only, the respective figures were RM 1,359,057 and RM 2,530,018. For QV combined strategy cost/QALY in the base case it was RM 4,937, reducing to RM 3,395 in the best case and rising to RM 7,992 in the worst case scenario. With the BV combined strategy, these three cost/QALYs were RM 6,624, RM 4,033 and RM 10,543. Incremental cost-effectiveness ratio (ICER) showed that screening at 70% coverage or higher was highly cost effective at RM 946.74 per QALYs saved but this was preceded by best case combined strategy with QV at RM 515.29 per QALYs saved. QV is more cost effective than BV. The QV combined strategy had a higher CE than

Estimating the public health importance of the CYD-tetravalent dengue vaccine: Vaccine preventable disease incidence and numbers needed to vaccinate.

PubMed

Gessner, Bradford D; Wilder-Smith, Annelies

2016-04-29

To evaluate the potential public health impact of the live attenuated tetravalent Sanofi Pasteur dengue vaccine (CYD-TDV) we analyzed data from the reported clinical trials to calculate vaccine preventable disease incidence (VPDI) and number needed to vaccinate (NNV) based on the licensure indication for persons age 9 years and above. VPDI is defined as incidence in an unvaccinated population X vaccine efficacy (VE), and thus incorporates both VE and the underlying burden of disease. NNV was calculated as 100,000 divided by VPDI divided by 2-year length of study. We compared these values to data for three newer vaccines that are currently integrated into some national immunization programs in Asia and Latin America, namely pneumococcal conjugate, Haemophilus influenzae type b, and rotavirus vaccines. In the Asian-Pacific trial, in the first 25 months after the first dose of the dengue vaccine, CYD-TDV prevented annually 2639 cases of virologically confirmed dengue for every 100,000 persons vaccinated, for an NNV of 18. In the Latin American trial, given the overall lower annual dengue incidence compared to Asia, VPDI was 1707, and NNV 28. For the Asian-Pacific and Latin American studies, the VPDIs for hospitalized virologically confirmed disease at the trials' end were 638 and 239 per 100,000 population per year, respectively, with NNVs of 75 and 201. VPDI for confirmed dengue hospitalization was higher than that for Hib vaccine against Hib meningitis or all cause severe pneumonia while lower than that for rotavirus vaccine against severe rotavirus gastroenteritis. Our analysis found that the CYD-TDV dengue vaccine had favorable VPDI and NNV, also when compared to existing vaccines used in Latin America and Asia. VPDI and NNV varied by serotype distribution, extent of prior dengue exposure (baseline seroprevalence) and country. These findings will help policy-makers decide where and how to introduce this vaccine post-licensure. Copyright © 2016 The Authors

A phase 1, open-label, randomized study to compare the immunogenicity and safety of different administration routes and doses of virosomal influenza vaccine in elderly.

PubMed

Levin, Yotam; Kochba, Efrat; Shukarev, Georgi; Rusch, Sarah; Herrera-Taracena, Guillermo; van Damme, Pierre

2016-10-17

Influenza remains a significant problem in elderly despite widespread vaccination coverage. This randomized, phase-I study in elderly compared different strategies of improving vaccine immunogenicity. A total of 370 healthy participants (⩾65years) were randomized equally 1:1:1:1:1:1 to six influenza vaccine treatments (approximately 60-63 participants per treatment arm) at day 1 that consisted of three investigational virosomal vaccine formulations at doses of 7.5, 15, and 45μg HA antigen/strain administered intradermally (ID) by MicronJet600™ microneedle device (NanoPass Technologies) or intramuscularly (IM), and three comparator registered seasonal vaccines; Inflexal V™ (Janssen) and MF59 adjuvanted Fluad™ (Novartis) administered IM and Intanza™ (Sanofi Pasteur) administered ID via Soluvia™ prefilled microinjection system (BD). Serological evaluations were performed at days 22 and 90 and safety followed-up for 6months. Intradermal delivery of virosomal vaccine using MicronJet600™ resulted in significantly higher immunogenicity than the equivalent dose of virosomal Inflexal V™ administered intramuscularly across most of the parameters and strains, as well as in some of the readouts and strains as compared with the 45μg dose of virosomal vaccine formulation. Of 370 participants, 300 (81.1%) reported ⩾1 adverse event (AE); more participants reported solicited local AEs (72.2%) than solicited systemic AEs (12.2%). Intradermal delivery significantly improved influenza vaccine immunogenicity compared with intramuscular delivery. Triple dose (45μg) virosomal vaccine did not demonstrate any benefit on vaccine's immunogenicity over 15μg commercial presentation. All treatments were generally safe and well-tolerated. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Comparative Evaluation of Vaccine Efficacy of Recombinant Marek's Disease Virus Vaccine Lacking Meq Oncogene in Commercial Chickens

USDA-ARS?s Scientific Manuscript database

Marek's disease virus oncogene meq has been identified as the gene involved in tumorigenesis in chickens. We have recently developed a Meq-null virus, rMd5delMeq, in which the oncogene Meq was deleted. Vaccine efficacy experiments conducted in ADOL 15I5 x 71 chickens vaccinated with rMd5delMeq virus...

Comparative evaluation of cell culture-adapted and chicken embryo-adapted fowl pox vaccine strains.

PubMed

Baxi, M K; Oberoi, M S

1999-01-01

Two types of vaccines, chicken embryo adapted (VacCE) and cell culture adapted (VacCC), were tested for their efficacy to elicite the immune response in birds vaccinated at 2 and 8 wk of age. The cell-mediated immune response studied by blastogenesis assay showed that birds vaccinated at the second week of age by both VacCE and VacCC vaccines had significant increase in T-lymphocyte count at 21 days postvaccination (PV) and 7 days postchallenge (PC), whereas in birds vaccinated at 8 wk of age, a significant increase was seen at 21 days PV and 7 days PC with the VacCC vaccine. The rise in passive hemagglutination titers was observed up to 21 days PV and 7 days PC in birds vaccinated at 2 wk of age. However, only the birds vaccinated with VacCC at 8 wk of age showed rise in titers at days 21 PV and 7 PC. Birds were challenged 90 days PV by scarification on the thigh region, and the birds vaccinated with VacCC showed 90% and 70% protection when vaccinated at 2 and 8 wk, respectively. The birds vaccinated with VacCE showed only 60% and 20% protection at the corresponding levels, respectively.

Human Papillomavirus (HPV) Vaccination and Adolescent Girls' Knowledge and Sexuality in Western Uganda: A Comparative Cross-Sectional Study.

PubMed

Turiho, Andrew Kampikaho; Muhwezi, Wilson Winston; Okello, Elialilia Sarikiaeli; Tumwesigye, Nazarius Mbona; Banura, Cecil; Katahoire, Anne Ruhweza

2015-01-01

The purpose of the study was to investigate the influence of human papillomavirus (HPV) vaccination on adolescent girls' knowledge of HPV and HPV vaccine, perception of sexual risk and intentions for sexual debut. This cross-sectional comparative study was conducted in Ibanda and Mbarara districts. Data was collected using a standardized self-administered questionnaire and analyzed using the Statistical Package for the Social Sciences computer software. Univariate, bivariate, and logistic regression analyses were conducted with significance level set at p < .05. Results showed that HPV vaccination was associated with being knowledgeable (Crude OR: 5.26, CI: 2.32-11.93; p = 0.000). Vaccination against HPV did not predict perception of sexual risk. Knowledge was low (only 87/385 or 22.6% of vaccinated girls were knowledgeable), but predicted perception of a high sexual risk (Adjusted OR: 3.12, CI: 1.37-3.63; p = 0.008). HPV vaccination, knowledge and perceived sexual risk did not predict sexual behaviour intentions. High parental communication was associated with adolescent attitudes that support postponement of sexual debut in both bivariate and multiple regression analyses. In conclusion, findings of this study suggest that HPV vaccination is not likely to encourage adolescent sexual activity. Influence of knowledge on sexual behaviour intentions was not definitively explained. Prospective cohort studies were proposed to address the emerging questions.

Comparing human papillomavirus vaccine concerns on Twitter: a cross-sectional study of users in Australia, Canada and the UK.

PubMed

Shapiro, Gilla K; Surian, Didi; Dunn, Adam G; Perry, Ryan; Kelaher, Margaret

2017-10-05

Opposition to human papillomavirus (HPV) vaccination is common on social media and has the potential to impact vaccine coverage. This study aims to conduct an international comparison of the proportions of tweets about HPV vaccines that express concerns, the types of concerns expressed and the social connections among users posting about HPV vaccines in Australia, Canada and the UK. Using a cross-sectional design, an international comparison of English language tweets about HPV vaccines and social connections among Twitter users posting about HPV vaccines between January 2014 and April 2016 was conducted. The Health Belief Model, one of the most widely used theories in health psychology, was used as the basis for coding the types of HPV vaccine concerns expressed on Twitter. The content of tweets and the social connections between users who posted tweets about HPV vaccines from Australia, Canada and the UK. 16 789 Twitter users who posted 43 852 tweets about HPV vaccines. The proportions of tweets expressing concern, the type of concern expressed and the proportions of local and international social connections between users. Tweets expressing concerns about HPV vaccines made up 14.9% of tweets in Canada, 19.4% in Australia and 22.6% in the UK. The types of concerns expressed were similar across the three countries, with concerns related to 'perceived barriers' being the most common. Users expressing concerns about HPV vaccines in each of the three countries had a relatively high proportion of international followers also expressing concerns. The proportions and types of HPV vaccine concerns expressed on Twitter were similar across the three countries. Twitter users who mostly expressed concerns about HPV vaccines were better connected to international users who shared their concerns compared with users who did not express concerns about HPV vaccines. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights

A comparative study of the incidence of aseptic meningitis in symptomatic natural mumps patients and monovalent mumps vaccine recipients in Japan.

PubMed

Nagai, Takao; Okafuji, Teruo; Miyazaki, Chiaki; Ito, Yuhei; Kamada, Makoto; Kumagai, Takuji; Yuri, Kenji; Sakiyama, Hiroshi; Miyata, Akiko; Ihara, Toshiaki; Ochiai, Hitoshi; Shimomura, Kunihisa; Suzuki, Eitaro; Torigoe, Sadayoshi; Igarashi, Masahiro; Kase, Tetsuo; Okuno, Yoshinobu; Nakayama, Tetsuo

2007-03-30

To compare the incidence of aseptic meningitis associated with symptomatic natural mumps infection and in mumps vaccine recipients, we conducted a prospective comparative study. Consecutive samples of 1051 children with mumps were enrolled by 10 pediatricians and 21,465 vaccine recipients by 143 pediatric primary care practitioners, from January 1, 2000 to January 1, 2003. Parents used a daily diary to record symptoms during the period of illness (15 days) or 30-day period following immunization. Mumps infection was confirmed by virus isolation and/or detection of mumps virus genome in salivary and CSF samples. The incidence of aseptic meningitis was 13/1051 (1.24%) in patients with symptomatic natural mumps infection and was estimated to be 0.7-1.1% of overall infection in considering asymptomatic infection, and 10/21,465 (0.05%) in vaccine recipients. Although aseptic meningitis is a clear side effect of the mumps vaccine, the incidence is considerably lower than among those with symptomatic natural infection. Our results provide an informative data for consideration to resume mumps vaccine as a part of routine immunization schedule for Japanese children.

Social regulations predispose people to complete vaccination for vaccine-preventable diseases.

PubMed

Takeuchi, Jiro; Goto, Masashi; Kawamura, Takashi; Hiraide, Atsushi

2014-11-01

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.

Vaccine knowledge and practices of primary care providers of exempt vs. vaccinated children

PubMed Central

Salmon, Daniel A.; Pan, William K.Y.; Omer, Saad B.; Navar, Ann Marie; Orenstein, Walter; Marcuse, Edgar K.; Taylor, James; deHart, M. Patricia; Stokley, Shannon; Carter, Terrell; Halsey, Neal A.

2014-01-01

Objectives: Compare vaccine knowledge, attitudes and practices of primary care providers for fully vaccinated children and children who are exempt from school immunization requirements. Methods: We conducted a mailed survey of parent-identified primary care providers from four states to measure perceived risks and benefits of vaccination and other key immunization beliefs. Frequencies of responses were stratified by type of provider, identified by exempt versus vaccinated children. Logistic regression was used to calculate odds ratios for responses by provider type. Results: 551 surveys were completed (84.3% response rate). Providers for exempt children had similar attitudes to providers for non-exempt children. However, there were statistically significant increased concerns among providers for exempt children regarding vaccine safety and lack of perceived individual and community benefits for vaccines compared to other providers. Conclusions: The great majority of providers for exempt children had similar attitudes about vaccine safety, effectiveness and benefits as providers of non-exempt children. Although providers for exempt children were more likely to believe that multiple vaccines weaken a child’s immune system and were concerned about vaccine safety and less likely to consider vaccines were beneficial, a substantial proportion of providers of both exempt and vaccinated children have concerns about vaccine safety and believe that CDC underestimates the frequency of vaccine side effects. Effective continuing education of providers about the risks and benefits of immunization and including in vaccine recommendations more information on pre and post licensing vaccine safety evaluations may help address these concerns. PMID:18424918

Childhood vaccines and Kawasaki disease, Vaccine Safety Datalink, 1996-2006.

PubMed

Abrams, Joseph Y; Weintraub, Eric S; Baggs, James M; McCarthy, Natalie L; Schonberger, Lawrence B; Lee, Grace M; Klein, Nicola P; Belongia, Edward A; Jackson, Michael L; Naleway, Allison L; Nordin, James D; Hambidge, Simon J; Belay, Ermias D

2015-01-03

Kawasaki disease is a childhood vascular disorder of unknown etiology. Concerns have been raised about vaccinations being a potential risk factor for Kawasaki disease. Data from the Vaccine Safety Datalink were collected on children aged 0-6 years at seven managed care organizations across the United States. Defining exposure as one of several time periods up to 42 days after vaccination, we conducted Poisson regressions controlling for age, sex, season, and managed care organization to determine if rates of physician-diagnosed and verified Kawasaki disease were elevated following vaccination compared to rates during all unexposed periods. We also performed case-crossover analyses to control for unmeasured confounding. A total of 1,721,186 children aged 0-6 years from seven managed care organizations were followed for a combined 4,417,766 person-years. The rate of verified Kawasaki disease was significantly lower during the 1-42 days after vaccination (rate ratio=0.50, 95% CL=0.27-0.92) and 8-42 days after vaccination (rate ratio=0.45, 95% CL=0.22-0.90) compared to rates during unexposed periods. Breaking down the analysis by vaccination category did not identify a subset of vaccines which was solely responsible for this association. The case-crossover analyses revealed that children with Kawasaki disease had lower rates of vaccination in the 42 days prior to symptom onset for both physician-diagnosed Kawasaki disease (rate ratio=0.79, 95% CL=0.64-0.97) and verified Kawasaki disease (rate ratio=0.38, 95% CL=0.20-0.75). Childhood vaccinations' studied did not increase the risk of Kawasaki disease; conversely, vaccination was associated with a transient decrease in Kawasaki disease incidence. Verifying and understanding this potential protective effect could yield clues to the underlying etiology of Kawasaki disease. Copyright © 2014. Published by Elsevier Ltd.

Targeted vaccination in healthy school children - Can primary school vaccination alone control influenza?

PubMed

Thorrington, Dominic; Jit, Mark; Eames, Ken

2015-10-05

The UK commenced an extension to the seasonal influenza vaccination policy in autumn 2014 that will eventually see all healthy children between the ages of 2-16 years offered annual influenza vaccination. Models suggest that the new policy will be both highly effective at reducing the burden of influenza as well as cost-effective. We explore whether targeting vaccination at either primary or secondary schools would be more effective and/or cost-effective than the current strategy. An age-structured deterministic transmission dynamic SEIR-type mathematical model was used to simulate a national influenza outbreak in England. Costs including GP consultations, hospitalisations due to influenza and vaccinations were compared to potential gains in quality-adjusted life years achieved through vaccinating healthy children. Costs and benefits of the new JCVI vaccination policy were estimated over a single season, and compared to the hypothesised new policies of targeted and heterogeneous vaccination. All potential vaccination policies were highly cost-effective. Influenza transmission can be eliminated for a particular season by vaccinating both primary and secondary school children, but not by vaccinating only one group. The most cost-effective policy overall is heterogeneous vaccination coverage with 48% uptake in primary schools and 34% in secondary schools. The Joint Committee on Vaccination and Immunisation can consider a modification to their policy of offering seasonal influenza vaccinations to all healthy children of ages 2-16 years. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparing the health and social protection effects of measles vaccination strategies in Ethiopia: An extended cost-effectiveness analysis.

PubMed

Driessen, Julia; Olson, Zachary D; Jamison, Dean T; Verguet, Stéphane

2015-08-01

Vaccination coverage rates often mask wide variation in access, uptake, and cost of providing vaccination. Financial incentives have been effective at creating demand for social services in a variety of settings. Using methods of extended cost-effectiveness analysis, we compare the health and economic implications of three different vaccine delivery strategies for measles vaccination in Ethiopia: i) routine immunization, ii) routine immunization with financial incentives, and iii) mass campaigns, known as supplemental immunization activities (SIAs). We examine annual birth cohorts of almost 3,000,000 births over a ten year period, exploring variation in these outcomes based on economic status to understand how various options may improve equity. SIAs naturally achieve higher levels of vaccine coverage, but at higher costs. Routine immunization combined with financial incentives bolsters demand among more economically vulnerable households. The relative appeal of routine immunization with financial incentives and SIAs will depend on the policy environment, including short-term financial limitations, time horizons, and the types of outcomes that are desired. While the impact of financial incentives has been more thoroughly studied in other policy arenas, such as education, consideration of this approach alongside standard vaccination models such as SIAs is timely given the dialog around measles eradication. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Vaccination of broiler chickens with dispersed dry powder vaccines as an alternative for liquid spray and aerosol vaccination.

PubMed

Corbanie, E A; Vervaet, C; van Eck, J H H; Remon, J P; Landman, W J M

2008-08-18

Vaccination of chickens with dispersable dry powder vaccines was compared with commercial liquid vaccines. A Clone 30 Newcastle disease vaccine virus was spray dried with mannitol or with a mixture of trehalose, polyvinylpyrrolidone and bovine serum albumin. A coarse (+/-30 microm) and fine (+/-7 microm) powder were produced with both formulations. A commercial reconstituted Clone 30 vaccine was applied as coarse liquid spray (+/-222 microm) or fine liquid aerosol (+/-24 microm). Reduction of virus concentration in the air after dispersion/nebulization was monitored by air sampling and was explained by sedimentation of coarse particles/droplets and evaporation of fine droplets. The vaccine formulations induced high haemagglutination inhibition antibody titres in the serum of 4-week-old broilers (2(7) at 4 weeks post-vaccination). The good serum antibody response with the fine liquid aerosol despite extensive inactivation of virus due to evaporation of droplets, suggested that powder formulations (without inactivation due to evaporation) might allow a significant reduction of vaccine dose, thereby offering new options for fine aerosol vaccination with low-titre vaccines.

Antibody responses to influenza a H1N1 vaccine compared to the circulating strain in influenza vaccine recipients during the 2013/2014 season in North America.

PubMed

Barron, Michelle A; Frank, Daniel N; Claypool, David; Ir, Diana; Ning, Mariangeli F; Curtis, Donna; Weinberg, Adriana

2016-10-01

Influenza strain A/California/07/2009 H1N1 (H1N1-09) reemerged in 2013/2014 as the predominant cause of illness. We sought to determine if antigenic drift may have contributed to the decreased responses to influenza vaccine. Fifty adults who received trivalent inactivated influenza vaccine (IIV3) and 56 children who received live attenuated quadrivalent influenza vaccine (LAIV4) had hemagglutination inhibition (HAI) and microneutralizing (MN) antibodies measured in plasma against H1N1-09 and H1N1 2013/2014 (H1N1-14) influenza. Partial sequencing of the hemagglutinin gene (nt 280-780) was performed on 38 clinical isolates and the vaccine prototype. In IIV3 recipients, HAI and MN titers against H1N1-14 were significantly lower than against H1N1-09 (p<0.0001 and 0.04, respectively). In LAIV4 recipients, only MN titers were significantly lower (p=0.02) for H1N1-09 compared with H1N1-14. A combined analysis showed significantly lower HAI and MN titers for H1N1-14 compared with H1N1-09 (p=0. 016 and 0.008, respectively). All 38 clinical isolates encoded the HA gene K166Q non-synonymous substitution; other non-synonymous substitutions were observed in <10% of the clinical isolates. 2013/2014 IIV3 and LAIV4 recipients had consistently lower MN antibody titers against H1N1-14 compared with H1N1-09. The HA K166Q mutation, located in a neutralizing epitope, probably contributed to these findings. Copyright © 2016 Elsevier B.V. All rights reserved.

Self-reported vaccination in the elderly

PubMed Central

Reyes-Ortiz, Carlos; Borda, Miguel German; Arciniegas, Antonio

2016-01-01

Objectives: To determine the frequency of vaccination in older adults within the city of Bogotá and to estimate the association with sociodemographic and health factors. Methods: This is a secondary data analysis from the SABE-Bogotá Study, a cross-sectional population-based study that included a total of 2,000 persons aged 60 years. Weighted percentages for self-reported vaccination [influenza, pneumococcal, tetanus] were determined. The association between vaccination and covariates was evaluate by logistic regression models. Results: A total of 73.0% of respondents received influenza, 57.8% pneumococcal and 47.6% tetanus vaccine. Factors independently associated with vaccination included: 1- age (65-74 years had higher odds of receiving vaccinations, compared to 60-64 years); 2- socioeconomic status (SES) (higher SES had lower odds of having influenza and pneumococcal vaccines, compared to those with lower SES); 3- health insurance (those with contributive or subsidized health insurance had higher odds (between 3 and 5 times higher) of having vaccinations, compared to those with no insurance); 4- older adults with better functional status (greater Lawton scores) had increased odds for all vaccinations; 5- older adults with higher comorbidity had increased odds for influenza and pneumococcal vaccinations. Conclusion: Vaccination campaigns should be strengthened to increase vaccination coverage, especially in the group more reticent to vaccination or vulnerable to reach it such as the disabled elder. PMID:27226661

Vaccines for preventing anthrax.

PubMed

Donegan, Sarah; Bellamy, Richard; Gamble, Carrol L

2009-04-15

Anthrax is a bacterial zoonosis that occasionally causes human disease and is potentially fatal. Anthrax vaccines include a live-attenuated vaccine, an alum-precipitated cell-free filtrate vaccine, and a recombinant protein vaccine. To evaluate the effectiveness, immunogenicity, and safety of vaccines for preventing anthrax. We searched the following databases (November 2008): Cochrane Infectious Diseases Group Specialized Register; CENTRAL (The Cochrane Library 2008, Issue 4); MEDLINE; EMBASE; LILACS; and mRCT. We also searched reference lists. We included randomized controlled trials (RCTs) of individuals and cluster-RCTs comparing anthrax vaccine with placebo, other (non-anthrax) vaccines, or no intervention; or comparing administration routes or treatment regimens of anthrax vaccine. Two authors independently considered trial eligibility, assessed risk of bias, and extracted data. We presented cases of anthrax and seroconversion rates using risk ratios (RR) and 95% confidence intervals (CI). We summarized immunoglobulin G (IgG) concentrations using geometric means. We carried out a sensitivity analysis to investigate the effect of clustering on the results from one cluster-RCT. No meta-analysis was undertaken. One cluster-RCT (with 157,259 participants) and four RCTs of individuals (1917 participants) met the inclusion criteria. The cluster-RCT from the former USSR showed that, compared with no vaccine, a live-attenuated vaccine (called STI) protected against clinical anthrax whether given by a needleless device (RR 0.16; 102,737 participants, 154 clusters) or the scarification method (RR 0.25; 104,496 participants, 151 clusters). Confidence intervals were statistically significant in unadjusted calculations, but when a small amount of association within clusters was assumed, the differences were not statistically significant. The four RCTs (of individuals) of inactivated vaccines (anthrax vaccine absorbed and recombinant protective antigen) showed a dose

Unintentional transfer of vaccinia virus associated with smallpox vaccines: ACAM2000(®) compared with Dryvax(®).

PubMed

Tack, Danielle M; Karem, Kevin L; Montgomery, Jay R; Collins, Limone; Bryant-Genevier, Marthe G; Tiernan, Rosemary; Cano, Maria; Lewis, Paige; Engler, Renata J M; Damon, Inger K; Reynolds, Mary G

2013-07-01

Routine vaccination against smallpox (variola) ceased in the US in 1976. However, in 2002 limited coverage for military personnel and some healthcare workers was reinstituted. In March 2008, ACAM2000® replaced Dryvax® as the vaccine used in the United States against smallpox. Unintentional transfer of vaccinia virus from a vaccination site by autoinoculation or contact transmission, can have significant public health implications. We summarize unintentional virus transfer AEs associated with ACAM2000® since March 2008 and compare with Dryvax®. We identified 309 reports for ACAM2000® with skin or ocular involvement, of which 93 were autoinoculation cases and 20 were contact transmission cases. The rate for reported cases of autoinoculation was 20.6 per 100,000 vaccinations and for contact transmission was 4.4 per 100,000 vaccinations. Eighteen contact transmission cases could be attributed to contact during a sporting activity (45%) or intimate contact (45%). Of the 113 unintentional transfer cases, 6 met the case definition for ocular vaccinia. The most common locations for all autoinoculation and contact cases were arm/elbow/shoulder (35/113; 31%) and face (24/113; 21%). Methods We reviewed 753 reports associated with smallpox in the Vaccine Adverse Event Reporting System and CDC Poxvirus consultation log, reported from March 2008 to August 2010. Reports were classified into categories based upon standard case definitions. Overall, unintentional transfer events for ACAM2000® and Dryvax® are similar. We recommend continued efforts to prevent transfer events and continuing education for healthcare providers focused on recognition of vaccinia lesions, proper sample collection, and laboratory testing to confirm diagnosis.

Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route.

PubMed

Carey, John B; Vrdoljak, Anto; O'Mahony, Conor; Hill, Adrian V S; Draper, Simon J; Moore, Anne C

2014-08-21

Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP1₄₂, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delivery. Microneedle-mediated vaccine priming and resultant induction of low anti-vector antibody titres permitted repeated use of the same adenovirus vaccine vector. This resulted in significantly increased antigen-specific antibody responses in these mice compared to ID-treated mice. Boosting with a heterologous vaccine; MVA-PyMSP1₄₂ also resulted in significantly greater antibody responses in mice primed with HAdV5-PyMSP1₄₂ using MN compared to the ID route. The highest protection against blood-stage malaria challenge was observed when a heterologous route of immunization (MN/ID) was used. Therefore, microneedle-mediated immunization has potential to both overcome some of the logistic obstacles surrounding needle-and-syringe-based immunization as well as to facilitate the repeated use of the same adenovirus vaccine thereby potentially reducing manufacturing costs of multiple vaccines. This could have important benefits in the clinical ease of use of adenovirus-based immunization strategies.

Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route

PubMed Central

Carey, John B.; Vrdoljak, Anto; O'Mahony, Conor; Hill, Adrian V. S.; Draper, Simon J.; Moore, Anne C.

2014-01-01

Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP142, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delivery. Microneedle-mediated vaccine priming and resultant induction of low anti-vector antibody titres permitted repeated use of the same adenovirus vaccine vector. This resulted in significantly increased antigen-specific antibody responses in these mice compared to ID-treated mice. Boosting with a heterologous vaccine; MVA-PyMSP142 also resulted in significantly greater antibody responses in mice primed with HAdV5-PyMSP142 using MN compared to the ID route. The highest protection against blood-stage malaria challenge was observed when a heterologous route of immunization (MN/ID) was used. Therefore, microneedle-mediated immunization has potential to both overcome some of the logistic obstacles surrounding needle-and-syringe-based immunization as well as to facilitate the repeated use of the same adenovirus vaccine thereby potentially reducing manufacturing costs of multiple vaccines. This could have important benefits in the clinical ease of use of adenovirus-based immunization strategies. PMID:25142082

Comparative Assessment of Transmission-Blocking Vaccine Candidates against Plasmodium falciparum

PubMed Central

Kapulu, M. C.; Da, D. F.; Miura, K.; Li, Y; Blagborough, A. M.; Churcher, T. S.; Nikolaeva, D.; Williams, A. R.; Goodman, A. L.; Sangare, I.; Turner, A. V.; Cottingham, M. G.; Nicosia, A.; Straschil, U.; Tsuboi, T.; Gilbert, S. C.; Long, Carole A.; Sinden, R. E.; Draper, S. J.; Hill, A. V. S.; Cohuet, A.; Biswas, S.

2015-01-01

Malaria transmission-blocking vaccines (TBVs) target the development of Plasmodium parasites within the mosquito, with the aim of preventing malaria transmission from one infected individual to another. Different vaccine platforms, mainly protein-in-adjuvant formulations delivering the leading candidate antigens, have been developed independently and have reported varied transmission-blocking activities (TBA). Here, recombinant chimpanzee adenovirus 63, ChAd63, and modified vaccinia virus Ankara, MVA, expressing AgAPN1, Pfs230-C, Pfs25, and Pfs48/45 were generated. Antibody responses primed individually against all antigens by ChAd63 immunization in BALB/c mice were boosted by the administration of MVA expressing the same antigen. These antibodies exhibited a hierarchy of inhibitory activity against the NF54 laboratory strain of P. falciparum in Anopheles stephensi mosquitoes using the standard membrane feeding assay (SMFA), with anti-Pfs230-C and anti-Pfs25 antibodies giving complete blockade. The observed rank order of inhibition was replicated against P. falciparum African field isolates in A. gambiae in direct membrane feeding assays (DMFA). TBA achieved was IgG concentration dependent. This study provides the first head-to-head comparative analysis of leading antigens using two different parasite sources in two different vector species, and can be used to guide selection of TBVs for future clinical development using the viral-vectored delivery platform. PMID:26063320

Understanding human papillomavirus vaccination intentions: comparative utility of the theory of reasoned action and the theory of planned behavior in vaccine target age women and men.

PubMed

Fisher, William A; Kohut, Taylor; Salisbury, Claire M A; Salvadori, Marina I

2013-10-01

Human papillomavirus (HPV) is an exceedingly prevalent sexually transmitted infection with serious medical, sexual, and relationship consequences. HPV vaccine protection is available but vaccine uptake is very inconsistent. This research applies two major theories of health behavior uptake, the Theory of Reasoned Action and the Theory of Planned Behavior, in an effort to understand intentions to receive HPV vaccine among vaccine target age women and men. The Theory of Reasoned Action asserts that attitudes toward HPV vaccination and perceptions of social support for HPV vaccination are the determinants of intentions to be vaccinated, whereas the Theory of Planned Behavior holds that attitudes toward vaccination, perceptions of social support for vaccination, and perceived ability to get vaccinated are the determinants of intentions to be vaccinated. Canadian university men (N=118) and women (N=146) in the HPV vaccine target age range took part in this correlational study online. Participants completed standard measures of attitudes toward HPV vaccination, perceptions of social support for vaccination, perceived ability to get vaccinated, beliefs about vaccination, and intentions to be vaccinated in the coming semester. Findings confirmed the propositions of the Theory of Reasoned Action and indicated that attitudes toward undergoing HPV vaccination and perceptions of social support for undergoing HPV vaccination contributed uniquely to the prediction of women's (R2=0.53) and men's (R2=0.44) intentions to be vaccinated in the coming semester. Clinical and public health education should focus on strengthening attitudes and perceptions of social support for HPV vaccination, and on the basic beliefs that appear to underlie attitudes and perceptions of social support for HPV vaccination, in efforts to promote HPV vaccine uptake. © 2013 International Society for Sexual Medicine.

DNA vaccines in veterinary use

PubMed Central

Redding, Laurel; Werner, David B

2015-01-01

DNA vaccines represent a new frontier in vaccine technology. One important application of this technology is in the veterinary arena. DNA vaccines have already gained a foothold in certain fields of veterinary medicine. However, several important questions must be addressed when developing DNA vaccines for animals, including whether or not the vaccine is efficacious and cost effective compared with currently available options. Another important question to consider is how to apply this developing technology in a wide range of different situations, from the domestic pet to individual fish in fisheries with several thousand animals, to wildlife programs for disease control. In some cases, DNA vaccines represent an interesting option for vaccination, while in others, currently available options are sufficient. This review will examine a number of diseases of veterinary importance and the progress being made in DNA vaccine technology relevant to these diseases, and we compare these with the conventional treatment options available. PMID:19722897

Improving rotavirus vaccine coverage: Can newer-generation and locally produced vaccines help?

PubMed Central

Kanungo, Suman; Anh, Dang Duc; Grais, Rebecca F.

2018-01-01

ABSTRACT There are two internationally available WHO-prequalified oral rotavirus vaccines (Rotarix and RotaTeq), two rotavirus vaccines licensed in India (Rotavac and Rotasiil), one in China (Lanzhou lamb rotavirus vaccine) and one in Vietnam (Rotavin-M1), and several candidates in development. Rotavirus vaccination has been rolled out in Latin American countries and is beginning to be deployed in sub-Saharan African countries but middle- and low-income Asian countries have lagged behind in rotavirus vaccine introduction. We provide a mini-review of the leading newer-generation rotavirus vaccines and compare them with Rotarix and RotaTeq. We discuss how the development and future availability of newer-generation rotavirus vaccines that address the programmatic needs of poorer countries may help scale-up rotavirus vaccination where it is needed. PMID:29135339

Safety and Immunogenicity of Sequential Rotavirus Vaccine Schedules

PubMed Central

Libster, Romina; McNeal, Monica; Walter, Emmanuel B.; Shane, Andi L.; Winokur, Patricia; Cress, Gretchen; Berry, Andrea A.; Kotloff, Karen L.; Sarpong, Kwabena; Turley, Christine B.; Harrison, Christopher J.; Pahud, Barbara A.; Marbin, Jyothi; Dunn, John; El-Khorazaty, Jill; Barrett, Jill

2016-01-01

BACKGROUND AND OBJECTIVES: Although both licensed rotavirus vaccines are safe and effective, it is often not possible to complete the schedule by using the same vaccine formulation. The goal of this study was to investigate the noninferiority of the immune responses to the 2 licensed rotavirus vaccines when administered as a mixed schedule compared with administering a single vaccine formulation alone. METHODS: Randomized, multicenter, open-label study. Healthy infants (6–14 weeks of age) were randomized to receive rotavirus vaccines in 1 of 5 different schedules (2 using a single vaccine for all doses, and 3 using mixed schedules). The group receiving only the monovalent rotavirus vaccine received 2 doses of vaccine and the other 4 groups received 3 doses of vaccine. Serum for immunogenicity testing was obtained 1 month after the last vaccine dose and the proportion of seropositive children (rotavirus immunoglobulin A ≥20 U/mL) were compared in all the vaccine groups. RESULTS: Between March 2011 and September 2013, 1393 children were enrolled and randomized. Immune responses to all the sequential mixed vaccine schedules were shown to be noninferior when compared with the 2 single vaccine reference groups. The proportion of children seropositive to at least 1 vaccine antigen at 1 month after vaccination ranged from 77% to 96%, and was not significantly different among all the study groups. All schedules were well tolerated. CONCLUSIONS: Mixed schedules are safe and induced comparable immune responses when compared with the licensed rotavirus vaccines given alone. PMID:26823540

Comparative evaluation of the immunogenicity of combined hepatitis A and B vaccine by a prospective and retrospective trial.

PubMed

Wolters, Bernd; Müller, Tobias; Ross, R Stefan; Clauberg, Ralf; Werfel, Uwe; Roggendorf, Hedwig; Siggelkow, Cornelius; Hausen, Thomas; Roggendorf, Michael

2009-04-01

In the past, immunogenicity of hepatitis A and B vaccines needed to be questioned in persons of advanced age, especially in those of 40 years and older. We performed a comparative multicenter prospective and retrospective study with the combined hepatitis A and B vaccine Twinrix to identify factors influencing the results of the vaccination in a population of all age groups. Out of 489 subjects enrolled, 241 were vaccinated in a prospective study (group 1) and 248 subjects in a retrospective study (group 2) in 17 German centers with median age of 40.1 (14-79) years. Following three applications of the combined hepatitis A/B vaccine we found 96.2% with protective antibodies against HAV and 88.7% were protected against HBV. With increasing age the subjects developed decreasing anti-HBs antibody levels whereas the seroprotection rate was significantly reduced by age (p < 0.05) in the retrospective study group only. Subjects with arterial hypertension and thyroid disease showed significantly decreased protection rates. The timing of the HBV antibody control seems to be important especially in low-responders because protective antibodies may drop below the detection limit within some month. The combined hepatitis A and B vaccine Twinrix proved to be highly effective against HBV, although antibody concentrations and seroprotection rates decreased with increasing age.

Vaccine Effectiveness - How Well Does the Seasonal Flu Vaccine Work?

MedlinePlus

... to determine the benefits of flu vaccination are “observational studies.” “Observational studies” compare the occurrence of flu illness in ... randomized. The measurement of vaccine effects in an observational study is referred to as “effectiveness.” Top of ...

[Pertussis in fully vaccinated infants and children. Are new vaccination strategies required?].

PubMed

Moraga-Llop, Fernando A; Mendoza-Palomar, Natàlia; Muntaner-Alonso, Antoni; Codina-Grau, Gemma; Fàbregas-Martori, Anna; Campins-Martí, Magda

2014-04-01

To analyse the vaccination status of children diagnosed with pertussis and to compare the clinical manifestations of fully vaccinated with unvaccinated, or incompletely-vaccinated, children. The clinical histories and vaccination cards of patients under 16years of age seen in the Emergency Room of the University Hospital Vall d'Hebron, Barcelona (Spain), for pertussis confirmed by a microbiological study were reviewed. The study period lasted from January 1, 2009 to December 31, 2011. Two hundred and twelve cases were studied: 35 in 2009, 28 in 2010 and 149 in 2011. RT-PCR was positive in 210 patients, and 73 had a positive culture. Infants under 6months of age account for 36.8% of all cases. Forty-four patients (21.5%) were not vaccinated. Forty-four (21.5%) children were between 2 and 5months of age and had received 1-2vaccine doses. One hundred and seventeen (57%) children were fully vaccinated; 76.9% (90cases) had received the last dose less than 4years ago. When clinical manifestations of the fully vaccinated patients were compared with those of the non-vaccinated or incompletely-vaccinated children, only cyanosis was found with a higher frequency in the latter group (P<.001). The age-adjusted probability of hospitalisation was significantly associated with non-vaccination (P=.001). The case mortality rate among inpatients was 1.3%. The number of pertussis cases seen in our centre has risen significantly in the last year. More than half (57%) of the patients were fully vaccinated, and 76.9% had received the last dose in the previous 4years. Other vaccination strategies, such as vaccination of adolescents, adults, and pregnant women, as well as a cocoon strategy are required to protect infants under 6months of age. More effective vaccines need to be developed. Copyright © 2012 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

The cost-effectiveness of rotavirus vaccination: Comparative analyses for five European countries and transferability in Europe.

PubMed

Jit, Mark; Bilcke, Joke; Mangen, Marie-Josée J; Salo, Heini; Melliez, Hugues; Edmunds, W John; Yazdan, Yazdanpanah; Beutels, Philippe

2009-10-19

Cost-effectiveness analyses are usually not directly comparable between countries because of differences in analytical and modelling assumptions. We investigated the cost-effectiveness of rotavirus vaccination in five European Union countries (Belgium, England and Wales, Finland, France and the Netherlands) using a single model, burden of disease estimates supplied by national public health agencies and a subset of common assumptions. Under base case assumptions (vaccination with Rotarix, 3% discount rate, health care provider perspective, no herd immunity and quality of life of one caregiver affected by a rotavirus episode) and a cost-effectiveness threshold of euro30,000, vaccination is likely to be cost effective in Finland only. However, single changes to assumptions may make it cost effective in Belgium and the Netherlands. The estimated threshold price per dose for Rotarix (excluding administration costs) to be cost effective was euro41 in Belgium, euro28 in England and Wales, euro51 in Finland, euro36 in France and euro46 in the Netherlands.

Is early measles vaccination better than later measles vaccination?

PubMed

Aaby, Peter; Martins, Cesário L; Ravn, Henrik; Rodrigues, Amabelia; Whittle, Hilton C; Benn, Christine S

2015-01-01

WHO recommends delaying measles vaccination (MV) until maternal antibody has waned. However, early MV may improve child survival by reducing mortality from conditions other than measles infection. We tested whether early MV improves child survival compared with later MV. We found 43 studies comparing measles-vaccinated and measles-unvaccinated children; however, only 16 studies had specific information that MV had been provided at 4-13 months of age, many before 9 months of age. In the 10 best studies (4 randomized trials and 6 observational studies) control children did not receive MV during follow-up. In eight of these studies the vaccine efficacy against death (VED) was 60% or more. In four studies with information on MV provided both before and after 12 months of age, the all-cause mortality reduction was significantly larger for children vaccinated in infancy (VED=74%; 95% CI 51-86%) than for children vaccinated after 12 months of age (VED=29%; CI 8-46%). Prevention of measles explained little of the reduction in mortality. In five studies with information on measles infection, VED was 67% (51-78%) and when measles deaths were excluded, VED was only reduced to 65% (47-77%). One natural experiment compared MV at 4-8 months versus MV at 9-11 months of age and found significantly lower all-cause mortality with early vaccination, the difference being 39% (8-60%). Child mortality may be reduced if MV is given earlier than currently recommended by international organizations. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Long-term Comparative Immunogenicity of Protein Conjugate and Free Polysaccharide Pneumococcal Vaccines in Chronic Obstructive Pulmonary Disease

PubMed Central

Dransfield, Mark T.; Harnden, Sarah; Burton, Robert L.; Albert, Richard K.; Bailey, William C.; Casaburi, Richard; Connett, John; Cooper, J. Allen D.; Criner, Gerard J.; Curtis, Jeffrey L.; Han, MeiLan K.; Make, Barry; Marchetti, Nathaniel; Martinez, Fernando J.; McEvoy, Charlene; Nahm, Moon H.; Niewoehner, Dennis E.; Porszasz, Janos; Reilly, John; Scanlon, Paul D.; Scharf, Steven M.; Sciurba, Frank C.; Washko, George R.; Woodruff, Prescott G.; Lazarus, Stephen C.

2012-01-01

Background. Although the 23-valent pneumococcal polysaccharide vaccine (PPSV23) protects against invasive disease in young healthy persons, randomized controlled trials in chronic obstructive pulmonary disease (COPD) have demonstrated no benefit in the intention-to-treat population. We previously reported that the 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) is safe and induced greater serotype-specific immunoglobulin G (IgG) and functional antibody than did PPSV23 1 month after vaccination. We hypothesized that these advantages would persist at 1 and 2 years. Methods. One hundred eighty-one patients with moderate to severe COPD were randomized to receive PPSV23 (n = 90) or PCV7 (1.0 mL; n = 91). We measured IgG by enzyme-linked immunosorbent assay and assessed functional antibody activity by a standardized opsonophagocytosis assay, reported as a killing index (OPK). We determined differences in IgG and OPK between vaccine groups at 1 and 2 years. Results. Relative to PPSV23, PCV7 induced greater OPK at both 1 and 2 years for 6 of 7 serotypes (not 19F). This response was statistically greater for 5 of 7 serotypes at 1 year and 4 of 7 at 2 years. Comparable differences in IgG were observed but were less often statistically significant. Despite meeting Centers for Disease Control and Prevention criteria for PPSV23 administration, almost 50% of individuals had never been vaccinated. No differences in the frequency of acute exacerbations, pneumonia, or hospitalization were observed. Conclusions. PCV7 induces a greater functional antibody response than PPSV23 in patients with COPD that persists for 2 years after vaccination. This superior functional response supports testing of conjugate vaccination in studies examining clinical end points. Clinical Trials Registration: NCT00457977. PMID:22652582

Efficacy of influenza vaccination and tamiflu® treatment--comparative studies with Eurasian Swine influenza viruses in pigs.

PubMed

Duerrwald, Ralf; Schlegel, Michael; Bauer, Katja; Vissiennon, Théophile; Wutzler, Peter; Schmidtke, Michaela

2013-01-01

Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebulisation with high doses of influenza virus A/swine/Potsdam/15/1981 (H1N1/1981, heterologous challenge to H1N1 vaccine strain) and A/swine/Bakum/1832/2000 (H1N2/2000, homologous challenge to H1N2 vaccine strain) in two independent trials. In each trial (i) 10 pigs were vaccinated twice with a trivalent vaccine (RESPIPORC® FLU3; 28 and 7 days before infection), (ii) another 10 pigs received 150 mg/day of Tamiflu® for 5 days starting 12 h before infection, and (iii) 12 virus-infected pigs were left unvaccinated and untreated and served as controls. Both viruses replicated efficiently in porcine respiratory organs causing influenza with fever, dyspnoea, and pneumonia. Tamiflu® treatment as well as vaccination prevented clinical signs and significantly reduced virus shedding. Whereas after homologous challenge with H1N2/2000 no infectious virus in lung and hardly any lung inflammation were detected, the virus titre was not and the lung pathology was only partially reduced in H1N1/1981, heterologous challenged pigs. Tamiflu® application did not affect these study parameters. In conclusion, all tested preventive measures provided protection against disease. Vaccination additionally prevented virus replication and histopathological changes in the lung of homologous challenged pigs.

Oral Cholera Vaccine Coverage, Barriers to Vaccination, and Adverse Events following Vaccination, Haiti, 2013.

PubMed

Tohme, Rania A; François, Jeannot; Wannemuehler, Kathleen; Iyengar, Preetha; Dismer, Amber; Adrien, Paul; Hyde, Terri B; Marston, Barbara J; Date, Kashmira; Mintz, Eric; Katz, Mark A

2015-06-01

In 2013, the first government-led oral cholera vaccination (OCV) campaign in Haiti was implemented in Petite Anse and Cerca Carvajal. To evaluate vaccination coverage, barriers to vaccination, and adverse events following vaccination, we conducted a cluster survey. We enrolled 1,121 persons from Petite Anse and 809 persons from Cerca Carvajal, categorized by 3 age groups (1-4, 5-14, >15 years). Two-dose OCV coverage was 62.5% in Petite Anse and 76.8% in Cerca Carvajal. Two-dose coverage was lowest among persons >15 years of age. In Cerca Carvajal, coverage was significantly lower for male than female respondents (69% vs. 85%; p<0.001). No major adverse events were reported. The main reason for nonvaccination was absence during the campaign. Vaccination coverage after this campaign was acceptable and comparable to that resulting from campaigns implemented by nongovernmental organizations. Future campaigns should be tailored to reach adults who are not available during daytime hours.

Effect of introduction of pentavalent vaccine as replacement for Diphtheria-Tetanus-Pertussis and Hepatitis B vaccines on vaccination uptake in a health facility in Nigeria.

PubMed

Sadoh, Ayebo Evawere; Nwaneri, Damian Uchechukwu; Ogboghodo, Bamidele Charity; Sadoh, Wilson Ehidiamen

2016-05-23

The introduction of a new vaccine into an immunization programme may affect the immunization system negatively or positively. The aim of this study is to determine the effect of the introduction of the pentavalent vaccine as replacement for DTP and Hepatitis B vaccines on timeliness, completion of the schedule and dropout rates among children attending a health facility. This was a retrospective cohort study which involved extracting immunization records of children attending the Institute of Child Health Child Welfare Clinic between June 2011 and May 2013. Pentavalent vaccine was introduced as a replacement for DTP and Hepatitis B vaccines in June 2012. The uptake, timeliness and dropout rates of different vaccines in the immunization schedule were determined for children who commenced immunization in the pre, peri and post introduction phases. A total of 1110 children were studied - 190, 410 and 510 who commenced vaccination in the pre, peri and post introduction phases of the pentavalent vaccine respectively. Uptake was significantly higher for all vaccines in the post introduction phase compared to pre and peri introduction phases (p<0.001). Completion of the immunization schedule by 60.2% of the children who commenced vaccination in the post introduction phase was higher than the 31.6% and 41.7% for the pre and peri introduction phases respectively (p<0.001). Significantly more visits were required to complete the schedule in the peri introduction phase compared to the pre and post introduction phases p<0.001. Delay in receipt of the three doses of DTP/PENTA was significantly longer in the peri introduction phase compared to pre and post introduction phases. The introduction of pentavalent vaccine significantly improved uptake of vaccines and completion of the schedule but resulted in prolonged delay in receipt of vaccines during the introduction period. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of Louisiana's HPV Vaccine Awareness Policy on HPV Vaccination Among 13- to 17-Year-Old Females.

PubMed

Pierre-Victor, Dudith; Trepka, Mary Jo; Page, Timothy F; Li, Tan; Stephens, Dionne P; Madhivanan, Purnima

2017-08-01

The Advisory Committee on Immunization Practices recommends routine human papillomavirus (HPV) immunization for 11- to 12-year-old adolescents. In 2008, Louisiana required the school boards to distribute HPV vaccine information to parents or guardian of students in Grades 6 to 12. This article investigates the impact of this policy on HPV vaccination among 13- to 17-year-old female adolescents using National Immunization Survey-Teen (NIS-Teen) data. Drawing on the data from the 2008 to 2012 NIS-Teen, we compared the difference in proportions of females who have been vaccinated before and after the policy. Using difference-indifference estimation, we explored the change in vaccination rates before and after the policy implementation in Louisiana compared with Alabama and Mississippi, two states that did not have such a policy in place. The difference-in-differences estimates for HPV vaccination were not significant. Physician recommendation for HPV vaccination was significantly associated with vaccination among females in Louisiana and Alabama (adjusted odds ratio [aOR] = 7.74; 95% confidence interval [CI; 5.22, 11.5]), and for those in Louisiana and Mississippi (aOR = 7.05; 95% CI [4.6, 10.5]). Compared to the proportion of female adolescents who had received physician recommendation in Alabama or Mississippi, the proportion in Louisiana did not increase significantly in the postpolicy period. HPV vaccination rates did not increase significantly in Louisiana compared to Alabama or Mississippi following the implementation of the policy. Despite Louisiana's policy, physician recommendation remains the key determinant of HPV vaccination. HPV vaccine awareness does not necessarily result in HPV vaccination.

Evaluation of human papilloma virus (HPV) vaccination strategies and vaccination coverage in adolescent girls worldwide.

PubMed

Owsianka, Barbara; Gańczak, Maria

2015-01-01

An analysis of HPV vaccination strategies and vaccination coverage in adolescent girls worldwide for the last eight years with regard to potential improvement of vaccination coverage rates in Poland. Literature search, covering the period 2006-2014, was performed using Medline. Comparative analysis of HPV vaccination strategies and coverage between Poland and other countries worldwide was conducted. In the last eight years, a number of countries introduced HPV vaccination for adolescent girls to their national immunization programmes. Vaccination strategies differ, consequently affecting vaccination coverage, ranging from several percent to more than 90%. Usually, there are also disparities at national level. The highest HPV vaccination coverage rates are observed in countries where vaccines are administered in school settings and funded from the national budget. Poland is one of the eight EU countries where HPV vaccination has not been introduced to mandatory immunization programme and where paid vaccination is only provided in primary health care settings. HPV vaccination coverage in adolescent girls is estimated at 7.5-10%. Disparities in HPV vaccination coverage rates in adolescent girls worldwide may be due to different strategies of vaccination implementation between countries. Having compared to other countries, the low HPV vaccination coverage in Polish adolescent girls may result from the lack of funding at national level and the fact that vaccines are administered in a primary health care setting. A multidimensional approach, involving the engagement of primary health care and school personnel as well as financial assistance of government at national and local level and the implementation of media campaigns, particularly in regions with high incidence of cervical cancer, could result in an increase of HPV vaccination coverage rates in Poland.

Effects of the introduction of new vaccines in Guinea-Bissau on vaccine coverage, vaccine timeliness, and child survival: an observational study.

PubMed

Fisker, Ane B; Hornshøj, Linda; Rodrigues, Amabelia; Balde, Ibraima; Fernandes, Manuel; Benn, Christine S; Aaby, Peter

2014-08-01

In 2008, the GAVI Alliance funded the introduction of new vaccines (including pentavalent diphtheria-tetanus-pertussis [DTP] plus hepatitis B and Haemophilus influenzae type b antigens) in Guinea-Bissau. The introduction was accompanied by increased vaccination outreach services and a more restrictive wastage policy, including only vaccinating children younger than 12 months. We assessed coverage of all vaccines in the Expanded Program on Immunizations before and after the new vaccines' introduction, and the implications on child survival. This observational cohort study used data from the Bandim Health Project, which has monitored vaccination status and mortality in randomly selected village clusters in Guinea-Bissau since 1990. We assessed the change in vaccination coverage using cohort data from children born in 2007 and 2009; analysed the proportion of children who received measles vaccine after 12 months of age using data from 1999-2006; and compared child mortality after age 12 months in children who had received measles vaccine and those who had not using data from 1999 to 2006. The proportion of children who were fully vaccinated by 12 months of age was 53% (468 of 878) in the 2007 cohort and 53% (467 of 879) in the 2009 cohort (relative risk [RR] 1·00, 95% CI 0·89-1·11). Coverage of DTP-3 and pentavalent-3 increased from 73% (644 of 878) in 2007 to 81% (712 of 879) in 2009 (RR 1·10, 95% CI 1·04 -1·17); by contrast, the coverage of measles vaccination declined from 71% (620 of 878) to 66% (577 of 879; RR 0·93, 0·85-1·01). The effect of the changes was significantly different for DTP-3 coverage compared with measles vaccine coverage (p=0·002). After 12 months of age, the adjusted mortality rate ratio was 0·71 (95% CI 0·56-0·90) for children who had received measles vaccine compared with those who had not (0·59 [0·43-0·80] for girls and 0·87 [0·62-1·23] for boys). The introduction of the new vaccination programme in 2008 was associated with

[Results of Booster Vaccination in Children with Primary Vaccine Failure after Initial Varicella Vaccination].

PubMed

Ozakiv, Takao; Nishimura, Naoko; Gotoh, Kensei; Funahashi, Keiji; Yoshii, Hironori; Okuno, Yoshinobu

2016-05-01

In October 2014, the varicella vaccination policy in Japan was changed from a single voluntary inoculation to two routine inoculations. This paper reports the results of booster vaccination in children who did not show seroconversion after initial vaccination (i.e., primary vaccine failure : PVF) over a 7-year period prior to the introduction of routine varicella vaccination. Between November 2007 and May 2014, 273 healthy children aged between 1.1 and 14.5 years (median : 1.7 years) underwent varicella vaccination. Before and 4 to 6 weeks after vaccination, the antibody titers were measured using an immune adherence hemagglutination (IAHA) assay and a glycoprotein-based enzyme-linked immunosorbent assay (gpELISA). In addition, side reactions were examined during the four-week period after vaccination. Children who did not show IAHA seroconversion (PVF) were recommended to receive a booster vaccination, and the measurement of antibody titers and an assessment of side reactions were performed after the booster dose. In May 2015, a questionnaire was mailed to each of the 273 participants to investigate whether they had developed varicella and/or herpes zoster after vaccination. After initial vaccination, the IAHA seroconversion rate was 75% and the mean antibody titer (Log2) with seroconversion was 4.7, while the gpELISA seroconversion rate was 84% and the mean antibody titer (Log10) with seroconversion was 2.4. Among children with PVF, 54 received booster vaccination within 81 to 714 days (median : 139 days) after the initial vaccination. After booster vaccination, the IAHA seroconversion rate was 98% and the mean antibody titer (Log2) with seroconversion was 5.8. Both the seroconversion rate and the antibody titer were higher compared with the values after the initial vaccination (p < 0.01). After booster vaccination, the gpELISA seropositive rate was 100% and the mean positive antibody titer (Log 10) was 3.6 ; similar results were obtained for the IAHA assay, with

Vaccination Coverage Cluster Surveys in Middle Dreib – Akkar, Lebanon: Comparison of Vaccination Coverage in Children Aged 12-59 Months Pre- and Post-Vaccination Campaign

PubMed Central

Assaad, Ramia; Rebeschini, Arianna; Hamadeh, Randa

2016-01-01

Introduction With the high proportion of refugee population throughout Lebanon and continuous population movement, it is sensible to believe that, in particular vulnerable areas, vaccination coverage may not be at an optimal level. Therefore, we assessed the vaccination coverage in children under 5 in a district of the Akkar governorate before and after a vaccination campaign. During the vaccination campaign, conducted in August 2015, 2,509 children were vaccinated. Materials and Methods We conducted a pre- and post-vaccination campaign coverage surveys adapting the WHO EPI cluster survey to the Lebanese MoPH vaccination calendar. Percentages of coverage for each dose of each vaccine were calculated for both surveys. Factors associated with complete vaccination were explored. Results Comparing the pre- with the post-campaign surveys, coverage for polio vaccine increased from 51.9% to 84.3%, for Pentavalent from 49.0% to 71.9%, for MMR from 36.2% to 61.0%, while the percentage of children with fully updated vaccination calendar increased from 32.9% to 53.8%. While Lebanese children were found to be better covered for some antigens compared to Syrians at the first survey, this difference disappeared at the post-campaign survey. Awareness and logistic obstacles were the primary reported causes of not complete vaccination in both surveys. Discussion Vaccination campaigns remain a quick and effective approach to increase vaccination coverage in crisis-affected areas. However, campaigns cannot be considered as a replacement of routine vaccination services to maintain a good level of coverage. PMID:27992470

Vaccine specific immune response to an inactivated oral cholera vaccine and EPI vaccines in a high and low arsenic area in Bangladeshi children.

PubMed

Saha, Amit; Chowdhury, Mohiul I; Nazim, Mohammad; Alam, Mohammad Murshid; Ahmed, Tanvir; Hossain, Mohammad Bakhtiar; Hore, Samar Kumar; Sultana, Gazi Nurun Nahar; Svennerholm, Ann-Mari; Qadri, Firdausi

2013-01-11

Immune responses to the inactivated oral whole cell cholera toxin B (CTB) subunit cholera vaccine, Dukoral(®), as well as three childhood vaccines in the national immunization system were compared in children living in high and low arsenic contaminated areas in Bangladesh. In addition, serum complement factors C3 and C4 levels were evaluated among children in the two areas. VACCINATIONS: Toddlers (2-5 years) were orally immunized with two doses of Dukoral 14 days apart. Study participants had also received diphtheria, tetanus and measles vaccines according to the Expanded Program on Immunization (EPI) in Bangladesh. The mean level of arsenic in the urine specimens in the children of the high arsenic area (HAA, Shahrasti, Chandpur) was 291.8μg/L while the level was 6.60μg/L in the low arsenic area (LAA, Mirpur, Dhaka). Cholera specific vibriocidal antibody responses were significantly increased in the HAA (87%, P<0.001) and the LAA (75%, P<0.001) children after vaccination with Dukoral, but no differences were found between the two groups. Levels of CTB specific IgA and IgG antibodies were comparable between the two groups, whereas LPS specific IgA and IgG were higher in the LAA group, although response rates were comparable. Diphtheria and tetanus vaccine specific IgG responses were significantly higher in the HAA compared to the LAA group (P<0.001, P=0.048 respectively), whereas there were no differences in the measles specific IgG responses between the groups. Complement C3 and C4 levels in sera were higher in participants from the HAA than the LAA groups (P<0.001, P=0.049 respectively). The study demonstrates that the oral cholera vaccine as well as the EPI vaccines studied are immunogenic in children in high and low arsenic areas in Bangladesh. The results are encouraging for the potential use of cholera vaccines as well as the EPI vaccines in arsenic endemic areas. Copyright © 2012 Elsevier Ltd. All rights reserved.

Impact of rotavirus vaccination in Germany: rotavirus surveillance, hospitalization, side effects and comparison of vaccines.

PubMed

Uhlig, Ulrike; Kostev, Karel; Schuster, Volker; Koletzko, Sibylle; Uhlig, Holm H

2014-11-01

Although rotavirus (RV) vaccination was licensed in 2006, it was not included into the officially recommended German childhood vaccination schedule until 2013. Local differences in health policies in the past led to large differences in vaccination coverage rate among the federal states of Germany. This enables an ecologic study of RV vaccine effectiveness. We performed a population-based retrospective analysis of RV vaccination use, RV notification and hospitalization among 0 to 5-year-old children in Germany during 2006 to 2011/2012. We compared effectiveness of the 2 RV vaccines, Rotateq and Rotarix, in an ambulatory setting and analyzed potential side effects. We observed a significant reduction in RV notifications since introduction of RV vaccination. In areas attaining vaccine coverage of 64%, RV-related hospital admissions of 0 and 1-year-old children decreased by 60% compared with 19% reduction in the low vaccination coverage area. Decrease in RV-related hospitalizations of 0 and 1-year-old children was specific and significantly associated with vaccination coverage of the individual federal state (P < 0.0001, r = -0.68). There was no overall increase in intussusception rate or Kawasaki disease-related hospital admissions since introduction of RV vaccination. The 2 licensed RV vaccines had similar effectiveness in the ambulatory setting. Postmarketing data suggest that RV vaccination is efficient in reducing RV-related hospitalizations. There is no apparent difference in effectiveness for Rotarix and Rotateq.

A preclinical study comparing approaches for augmenting the immunogenicity of a heptavalent KLH-conjugate vaccine against epithelial cancers.

PubMed

Ragupathi, Govind; Koide, Fusataka; Sathyan, Natarajan; Kagan, Ella; Spassova, Maria; Bornmann, William; Gregor, Polly; Reis, Celso A; Clausen, Henrik; Danishefsky, Samuel J; Livingston, Philip O

2003-10-01

Previously using a series of monovalent vaccines, we demonstrated that the optimal method for inducing an antibody response against cancer cell-surface antigens is covalent conjugation of the antigens to keyhole limpet hemocyanin (KLH) and the use of a saponin adjuvant. We have prepared a heptavalent-KLH conjugate vaccine containing the seven epithelial cancer antigens GM2, Globo H, Lewis(y), TF(c), Tn(c), STn(c), and glycosylated MUC1. In preparation for testing this vaccine in the clinic, we tested the impact on antibody induction of administering the individual conjugates plus adjuvant compared with a mixture of the seven conjugates plus adjuvant, and of several variables thought to augment immunogenicity. These include approaches for decreasing suppressor cell activity or increasing helper T-lymphocyte activity (low dose cyclophosphamide or anti-CTLA-4 MAb), different saponin adjuvants at various doses (QS-21 and GPI-0100), and different methods of formulation (lyophilization and use of polysorbate 80). We find that: (1). Immunization with the heptavalent-KLH conjugate plus GPI-0100 vaccine induces antibodies against the seven antigens of comparable titer to those induced by the individual-KLH conjugate vaccines, high titers of antibodies against Tn (median ELISA titer IgM/IgG 320/10240), STn (640/5120), TF (320/10240), MUC1 (80/20480), and globo H (640/40); while lower titers of antibodies against Lewis(y)()(160/0) and only occasional antibodies against GM2 are induced. (2). These antibodies reacted with the purified synthetic antigens by ELISA, and with naturally expressed antigens on the cancer cell surface by FACS. (3). None of the approaches for further altering the suppressor cell/helper T-cell balance nor changes to the standard formulation by lyophilization or use of polysorbate 80 had any impact on antibody titers. (4). An optimal dose of saponin adjuvant, QS-21 (50 microg) or GPI-0100 (1000 microg), is required for optimal antibody titers. This

First-in-human safety and immunogenicity investigations of three adjuvanted reduced dose inactivated poliovirus vaccines (IPV-Al SSI) compared to full dose IPV Vaccine SSI when given as a booster vaccination to adolescents with a history of IPV vaccination at 3, 5, 12months and 5years of age.

PubMed

Lindgren, Line M; Tingskov, Pernille N; Justesen, Annette H; Nedergaard, Bettina S; Olsen, Klaus J; Andreasen, Lars V; Kromann, Ingrid; Sørensen, Charlotte; Dietrich, Jes; Thierry-Carstensen, Birgit

2017-01-23

There is a demand of affordable IPV in the World. Statens Serum Institut (SSI) has developed three reduced dose IPV formulations adsorbed to aluminium hydroxide; 1/3 IPV-Al, 1/5 IPV-Al and 1/10 IPV-Al SSI, and now report the results of the first investigations in humans. 240 Danish adolescents, aged 10-15years, and childhood vaccinated with IPV were booster vaccinated with 1/3 IPV-Al, 1/5 IPV-Al, 1/10 IPV-Al or IPV Vaccine SSI. The booster effects (GMTRs) of the three IPV-Al SSI were compared to IPV Vaccine SSI, and evaluated for non-inferiority. The pre-vaccination GMTs were similar across the groups; 926 (type 1), 969 (type 2) and 846 (type 3) in the total trial population. The GMTRs by poliovirus type and IPV formulation were: Type 1: 17.0 (1/3 IPV-Al), 13.0 (1/5 IPV-Al), 7.1 (1/10 IPV-Al) and 42.2 (IPV Vaccine SSI). Type 2: 12.5 (1/3 IPV-Al), 13.1 (1/5 IPV-Al), 7.6 (1/10 IPV-Al) and 47.8 (IPV Vaccine SSI). Type 3: 14.5 (1/3 IPV-Al), 16.2 (1/5 IPV-Al), 8.9 (1/10 IPV-Al) and 62.4 (IPV Vaccine SSI) Thus, the three IPV-Al formulations were highly immunogenic, but inferior to IPV Vaccine SSI, in this booster vaccination trial. No SAE and no AE of severe intensity occurred. 59.2% of the subjects reported at least one AE. Injection site pain was the most frequent AE in all groups; from 24.6% to 43.3%. Injection site redness and swelling frequencies were<5% in most and<10% in all groups. The most frequent systemic AEs were fatigue (from 8.2% to 15.0%) and headache (from 15.0% to 28.3%). Most AEs were of mild intensity. In conclusion, the three IPV-Al SSI were safe in adolescents and the booster effects were satisfactory. ClinicalTrials.gov registration number: NCT02280447. Copyright © 2016. Published by Elsevier Ltd.

Comparative safety, immunogenicity, and efficacy of several anti-H5N1 influenza experimental vaccines in a mouse and chicken models (Testing of killed and live H5 vaccine).

PubMed

Gambaryan, Alexandra S; Lomakina, Natalia F; Boravleva, Elizaveta Y; Kropotkina, Ekaterina A; Mashin, Vadim V; Krasilnikov, Igor V; Klimov, Alexander I; Rudenko, Larisa G

2012-05-01

Parallel testing of inactivated (split and whole virion) and live vaccine was conducted to compare the immunogenicity and protective efficacy against homologous and heterosubtypic challenge by H5N1 highly pathogenic avian influenza virus. Four experimental live vaccines based on two H5N1 influenza virus strains were tested; two of them had hemagglutinin (HA) of A/Vietnam/1203/04 strain lacking the polybasic HA cleavage site, and two others had hemagglutinins from attenuated H5N1 virus A/Chicken/Kurgan/3/05, with amino acid substitutions of Asp54/Asn and Lys222/Thr in HA1 and Val48/Ile and Lys131/Thr in HA2 while maintaining the polybasic HA cleavage site. The neuraminidase and non-glycoprotein genes of the experimental live vaccines were from H2N2 cold-adapted master strain A/Leningrad/134/17/57 (VN-Len and Ku-Len) or from the apathogenic H6N2 virus A/Gull/Moscow/3100/2006 (VN-Gull and Ku-Gull). Inactivated H5N1 and H1N1 and live H1N1 vaccine were used for comparison. All vaccines were applied in a single dose. Safety, immunogenicity, and protectivity against the challenge with HPAI H5N1 virus A/Chicken/Kurgan/3/05 were estimated. All experimental live H5 vaccines tested were apathogenic as determined by weight loss and conferred more than 90% protection against lethal challenge with A/Chicken/Kurgan/3/05 infection. Inactivated H1N1 vaccine in mice offered no protection against challenge with H5N1 virus, while live cold-adapted H1N1 vaccine reduced the mortality near to zero level. The high yield, safety, and protectivity of VN-Len and Ku-Len made them promising strains for the production of inactivated and live vaccines against H5N1 viruses. © 2011 Blackwell Publishing Ltd.

Comparative analysis of the immunologic response induced by the Sterne 34F2 live spore Bacillus anthracis vaccine in a ruminant model.

PubMed

Ndumnego, Okechukwu C; Köhler, Susanne M; Crafford, Jannie; van Heerden, Henriette; Beyer, Wolfgang

2016-10-01

The Sterne 34F2 live spore vaccine (SLSV) developed in 1937 is the most widely used veterinary vaccine against anthrax. However, literature on the immunogenicity of this vaccine in a target ruminant host is scarce. In this study, we evaluated the humoral response to the Bacillus anthracis protective antigen (rPA), a recombinant bacillus collagen-like protein of anthracis (rBclA), formaldehyde inactivated spores (FIS) prepared from strain 34F2 and a vegetative antigen formulation prepared from a capsule and toxin deficient strain (CDC 1014) in Boer goats. The toxin neutralizing ability of induced antibodies was evaluated using an in vitro toxin neutralization assay. The protection afforded by the vaccine was also assessed in vaccinates. Anti-rPA, anti-FIS and lethal toxin neutralizing titres were superior after booster vaccinations, compared to single vaccinations. Qualitative analysis of humoral responses to rPA, rBclA and FIS antigens revealed a preponderance of anti-FIS IgG titres following either single or double vaccinations with the SLSV. Antibodies against FIS and rPA both increased by 350 and 300-fold following revaccinations respectively. There was no response to rBclA following vaccinations with the SLSV. Toxin neutralizing titres increased by 80-fold after single vaccination and 700-fold following a double vaccination. Lethal challenge studies in naïve goats indicated a minimum infective dose of 36 B. anthracis spores. Single and double vaccination with the SLSV protected 4/5 and 3/3 of goats challenged with>800 spores respectively. An early booster vaccination following the first immunization is suggested in order to achieve a robust immunity. Results from this study indicate that this crucial second vaccination can be administered as early as 3 months after the initial vaccination. Copyright © 2016 Elsevier B.V. All rights reserved.

Parents with doubts about vaccines: which vaccines and reasons why.

PubMed

Gust, Deborah A; Darling, Natalie; Kennedy, Allison; Schwartz, Ben

2008-10-01

The goals were (1) to obtain national estimates of the proportions of parents with indicators of vaccine doubt, (2) to identify factors associated with those parents, compared with parents reporting no vaccine doubt indicators, (3) to identify the specific vaccines that prompted doubt and the reasons why, and (4) to describe the main reasons parents changed their minds about delaying or refusing a vaccine for their child. Data were from the National Immunization Survey (2003-2004). Groups included parents who ever got a vaccination for their child although they were not sure it was the best thing to do ("unsure"), delayed a vaccination for their child ("delayed"), or decided not to have their child get a vaccination ("refused"). A total of 3924 interviews were completed. Response rates were 57.9% in 2003 and 65.0% in 2004. Twenty-eight percent of parents responded yes to ever experiencing >or=1 of the outcome measures listed above. In separate analyses for each outcome measure, vaccine safety concern was a predictor for unsure, refused, and delayed parents. The largest proportions of unsure and refused parents chose varicella vaccine as the vaccine prompting their concern, whereas delayed parents most often reported "not a specific vaccine" as the vaccine prompting their concern. Most parents who delayed vaccines for their child did so for reasons related to their child's illness, unlike the unsure and refused parents. The largest proportion of parents who changed their minds about delaying or not getting a vaccination for their child listed "information or assurances from health care provider" as the main reason. Parents who exhibit doubts about immunizations are not all the same. This research suggests encouraging children's health care providers to solicit questions about vaccines, to establish a trusting relationship, and to provide appropriate educational materials to parents.

Prolonging herd immunity to cholera via vaccination: Accounting for human mobility and waning vaccine effects

PubMed Central

Buckee, Caroline O.

2018-01-01

Background Oral cholera vaccination is an approach to preventing outbreaks in at-risk settings and controlling cholera in endemic settings. However, vaccine-derived herd immunity may be short-lived due to interactions between human mobility and imperfect or waning vaccine efficacy. As the supply and utilization of oral cholera vaccines grows, critical questions related to herd immunity are emerging, including: who should be targeted; when should revaccination be performed; and why have cholera outbreaks occurred in recently vaccinated populations? Methods and findings We use mathematical models to simulate routine and mass oral cholera vaccination in populations with varying degrees of migration, transmission intensity, and vaccine coverage. We show that migration and waning vaccine efficacy strongly influence the duration of herd immunity while birth and death rates have relatively minimal impacts. As compared to either periodic mass vaccination or routine vaccination alone, a community could be protected longer by a blended “Mass and Maintain” strategy. We show that vaccination may be best targeted at populations with intermediate degrees of mobility as compared to communities with very high or very low population turnover. Using a case study of an internally displaced person camp in South Sudan which underwent high-coverage mass vaccination in 2014 and 2015, we show that waning vaccine direct effects and high population turnover rendered the camp over 80% susceptible at the time of the cholera outbreak beginning in October 2016. Conclusions Oral cholera vaccines can be powerful tools for quickly protecting a population for a period of time that depends critically on vaccine coverage, vaccine efficacy over time, and the rate of population turnover through human mobility. Due to waning herd immunity, epidemics in vaccinated communities are possible but become less likely through complementary interventions or data-driven revaccination strategies. PMID:29489815

Immunogenicity, Safety and Antibody Persistence of a Booster Dose of Quadrivalent Meningococcal ACWY-tetanus Toxoid Conjugate Vaccine Compared with Monovalent Meningococcal Serogroup C Vaccine Administered Four Years After Primary Vaccination Using the Same Vaccines.

PubMed

Vesikari, Timo; Forsten, Aino; Bianco, Veronique; Van der Wielen, Marie; Miller, Jacqueline M

2015-12-01

We evaluated safety, immunogenicity and antibody persistence of meningococcal serogroups A, C, W and Y tetanus toxoid conjugate vaccine (MenACWY-TT) booster vaccination 4 years after priming of toddlers. This phase III, open-label, controlled study in Finland (NCT00955682) enrolled children previously randomized (3:1) at 12-23 months (NCT00474266) to receive 1 dose of MenACWY-TT or MenC conjugate vaccine (MenC-CRM197). Serum bactericidal antibody titers using rabbit (rSBA, cut-off 1:8) and human complement (hSBA, cut-off 1:8) were assessed at year 3 and 4 after priming and 1 month and 1 year after administration of a booster dose of the same vaccine given for primary vaccination. Reactogenicity and safety were assessed, and vaccination-related serious adverse events were recorded from the time of primary vaccination. Before booster (year 4), 74.1%, 40.4%, 49.3% and 58.2% of MenACWY-TT-recipients retained rSBA titers ≥1:8 for serogroups A, C, W and Y, respectively; 28.8%, 73.2%, 80.6% and 65.4% retained hSBA ≥1:8. Percentages for the MenC-CRM group were 35.6% (rSBA-MenC) and 46.9% (hSBA-MenC). After MenACWY-TT booster, ≥99.5% had rSBA ≥1:8 and hSBA ≥1:8 for each serogroup. After MenC-CRM197 booster, all children had rSBA-MenC ≥1:8 and hSBA-MenC ≥1:8. At year 5, percentages above the cut-off were ≥97.4% (rSBA) and ≥95.5% (hSBA) in MenACWY-TT-vaccinees for each serogroup. The MenACWY-TT booster dose had a clinically acceptable safety profile. No vaccine-related serious adverse events were reported. There was evidence of antibody persistence 4 years after toddlers were primed with MenACWY-TT. Booster vaccination induced robust immune responses for all serogroups with an acceptable safety profile.

Private-sector vaccine purchase costs and insurer payments: a disincentive for using combination vaccines?

PubMed

Clark, Sarah J; Cowan, Anne E; Freed, Gary L

2011-04-01

Combination vaccines have been endorsed as a means to decrease the number of injections needed to complete the childhood immunization schedule, yet anecdotal reports suggest that private providers lose money on combination vaccines. The objective of this study was to determine whether practices purchasing combination vaccines had significantly different vaccine costs and reimbursement compared to practices that were not purchasing combination vaccines. Using cross-sectional purchase and insurer payment data collected from a targeted sample of private practices in five US states, we calculated the average total vaccine cost and reimbursement across the childhood immunization schedule. The average vaccine purchase cost across the childhood schedule was significantly higher for practices using a combined vaccine with diphtheria, tetanus, acellular pertussis vaccine, inactivated polio vaccine, and Hepatitis B vaccine (DTaP-IPV-HepB) than for practices using either separate vaccine products or a combined vaccine with Haemophilus influenzae, type b vaccine and Hepatitis B vaccine (Hib-HepB). The average insurer payment for vaccine administration across the childhood schedule was significantly lower for practices using DTaP-IPV-HepB combination vaccine than for practices using separate vaccine products. This study appears to validate anecdotal reports that vaccine purchase costs and insurer payment for combination vaccines can have a negative financial impact for practices that purchase childhood vaccines.

Comparing the immunogenicity and safety of 3 Japanese encephalitis vaccines in Asia-Pacific area: A systematic review and meta-analysis.

PubMed

Wang, Shi-Yuan; Cheng, Xiao-Hua; Li, Jing-Xin; Li, Xi-Yan; Zhu, Feng-Cai; Liu, Pei

2015-01-01

Japanese encephalitis virus (JEV), a leading cause of Japanese encephalitis (JE) in children and adults, is a major public health problem in Asian countries. This study reports a meta-analysis of the immunogenicity and safety of vaccines used to protect infants or children from JE. Three types of JE vaccine were examined, namely, Japanese encephalitis live-attenuated vaccine (JEV-L), Japanese encephalitis inactivated vaccine (Vero cell) (JEV-I(Vero)), and Japanese encephalitis inactivated vaccine (primary hamster kidney cell) (JEV-I(PHK)). These vaccines are used to induce fundamental immunity against JE; however, few studies have compared their immunogenicity and safety in infants and young children less than 2 years of age. Data were obtained by searching 5 databases: Web of Science, PubMed, China National Knowledge Infrastructure, the China Wanfang database, and the Cochrane database. Fifteen articles were identified and scored using the Jadad score for inclusion in the meta-analysis. Random effect models were used to calculate the pooled seroconversion rate and adverse reaction rate when tests for heterogeneity were significant. The results showed that the pooled seroconversion rate for JEV-I(PHK) (62.23%) was lower than that for JEV-I(Vero) (86.49%) and JEV-L (83.52%), and that the pooled adverse reaction rate for JEV-L (18.09%) was higher than that for JEV-I(PHK) (10.08%) and JEV-I(Vero) (12.49%). The pooled relative risk was then calculated to compare the seroconversion and adverse reaction rates. The results showed that JEV-I(Vero) and JEV-L were more suitable than JEV-I(PHK) for inducing fundamental immunity to JE in infants and children less than 2 years of age.

Rural parents' vaccination-related attitudes and intention to vaccinate middle and high school children against influenza following educational influenza vaccination intervention

PubMed Central

Painter, Julia E.; Pazol, Karen; Gargano, Lisa M.; Orenstein, Walter; Hughes, James M.; DiClemente, Ralph J.

2011-01-01

Objective: This study examined changes in parental influenza vaccination attitudes and intentions after participating in school-based educational influenza vaccination intervention. Methods: Participants were drawn from three counties participating in a school-based influenza vaccination intervention in rural Georgia (baseline N=324; follow-up N=327). Data were collected pre- and post-intervention from phone surveys with parents’ with children attending middle- and high-school. Attitudes, beliefs, vaccination history, and intention to vaccinate were assessed.  Results:  Parents who participated in the intervention conditions reported significantly higher influenza vaccination rates in their adolescents, relative to a control group, as well as increased vaccination rates post-intervention participation relative to their baseline rates. Intervention participants reported greater intention to have their adolescent vaccinated in the coming year compared to control parents.  Significant differences were observed post intervention in perceived barriers and benefits of vaccination. Conclusions: These findings suggest that a school-delivered educational influenza vaccination intervention targeting parents and teens may influence influenza vaccination in rural communities. Future influenza vaccination efforts geared toward the parents of rural middle- and high-school students may benefit from addressing barriers and benefits of influenza vaccination. PMID:22048112

Antibody response in cattle after vaccination with inactivated and attenuated rabies vaccines.

PubMed

Rodrigues da Silva, A C; Caporale, G M; Gonçalves, C A; Targueta, M C; Comin, F; Zanetti, C R; Kotait, I

2000-01-01

Despite the absence of current official reports showing the number of cattle infected by rabies, it is estimated that nearly 30,000 bovines are lost each year in Brazil. In order to minimize the important economic losses, control of the disease is achieved by eliminating bat colonies and by herd vaccination. In this study, we compare the antibody response in cattle elicited by vaccination with an attenuated ERA vaccine (AEvac) and an inactivated-adjuvanted PV (IPVvac) vaccine. The antibody titers were appraised by cell-culture neutralization test and ELISA, and the percentage of seropositivity was ascertained for a period of 180 days. IPVvac elicited complete seropositivity rates from day 30 to day 150, and even on day 180, 87% of the sera showed virus-neutralizing antibody titers (VNA) higher than 0.5IU/ml. There were no significant differences between the VNA titers and seropositivity rates obtained with IPVvac in the two methods tested. AEvac, however, elicited significantly lower titers than those observed in the group receiving inactivated vaccine. In addition, the profiles of antirabies IgG antibodies, evaluated by ELISA, and VNA, appraised by cell-culture neutralization test, were slightly different, when both vaccines were compared.

[Comparative evaluation of neurovirulence of domestic and foreign live mumps vaccine].

PubMed

Maksimova, O A; Popov, V F; Bektimirov, T A; Grigor'eva, L V; Iunasova, T N; Kaplunova, O P; Sharova, O K

2001-01-01

Morphological and immunofluorescent study of changes in the central nervous system of monkeys with mumps was carried out in order to determine the criteria of neurovirulence of different mumps virus strains. Quantitative evaluation showed a lower residual neurovirulence of L-3 strain vs. Jeryl Lynn and Urabe Am9 strains. Use of new methodological approaches to evaluation of mumps vaccine strain neurovirulence will improve the safety control of live mumps vaccines.

Rapid immunization effects of a new type of 60 μg hepatitis B vaccine compared with traditional 20 μg hepatitis B vaccines in adults.

PubMed

Wang, Huai; Cai, Binyu; Rao, Delong; Liu, Min; Li, Yabin; Liang, Xiaofeng; Cui, Fuqiang; Zhang, Guomin; Wang, Fuzhen; Pang, Xinghuo; Nie, Li; Qiu, Qian; Wu, Jiang; Li, Liqiu; Huang, Fang; Zhang, Wei

2016-11-01

The widely recommended standard schedule of hepatitis B vaccine for adults is months 0, 1 and 6, which takes 6 months to complete. Rapid completion of one vaccination schedule is important to adults because of its low compliance with follow-up doses. A new type of 60 μg Hepatitis B vaccine, made by Shenzhen Kangtai Biological Products Co., LTD., is originally recommended for low or non-responders. The objective of this clinical trial was to test whether this 60 μg hepatitis B vaccine could be used in primary immune population and what is its level of immunogenicity and safety compared with other hepatitis B vaccines. This is a 2-center randomized controlled study. A total of 1169 healthy adults aged between 25 and 55 who tested negative for HBsAg, anti-HBs, and anti-HBc were eligible for the study and were enrolled from relatively fixed and stable sites, such as villages, schools and large enterprises et al in Xuanhua county in Hebei province and Huaibei county in Anhui province. They were randomized to group A (20 μg Engerix-B® with 0, 1, 6 month intervals), group B (20 μg Kangtai hepatitis B vaccine with 0, 1, 6 month intervals), group C (60 μg Kangtai hepatitis B vaccine with 0, 2 month intervals) and group D (20 μg Huabei hepatitis B vaccine made by recombinant DNA techniques in CHO cell with 0, 1, 6 month intervals). In group A, B and D, every study object's blood sample was collected in the second month after their final injection to test the anti-HBs levels; while in group C, the blood sample was collected in the second month after the first and the second injection to test the anti-HBs levels. Adverse events were collected after each dose to assess the vaccines' safety. The seroprotection rates were 93.17%, 97.23%, 93.54% and 98.98% respectively and the geometric mean titers (GMTs) were 1033.38 mIU/ml, 600.75 mIU/ml, 265.69 mIU/ml and 1627.05 mIU/ml in group A,B,C and D respectively. The difference of seroprotection rate among the 4

Knowledge of HPV infection and vaccination among vaccinated and unvaccinated teenaged girls.

PubMed

Sopracordevole, Francesco; Cigolot, Federica; Mancioli, Francesca; Agarossi, Alberto; Boselli, Fausto; Ciavattini, Andrea

2013-07-01

To assess the knowledge of teenaged girls on human papillomavirus (HPV) infection and vaccination 12 months after the start of a vaccine administration and information campaign. Between May 15 and June 15, 2009, an anonymous questionnaire was given to 629 girls attending a secondary school in a northeastern Italian city (286 were vaccinated against HPV, 343 were unvaccinated) to investigate their knowledge on HPV infection, transmission, prevention, vaccination, and post-vaccination behaviors. The responses were evaluated with respect to the vaccination status of the participants. Vaccinated teenaged girls had no more knowledge than unvaccinated ones about the route of HPV transmission, and the relationship between HPV and AIDS. Vaccinated girls had less knowledge than unvaccinated girls about preventing transmission by condom (P=0.003) and about the correlation between HPV and penile cancer (P=0.034) and warts (P=0.001). Furthermore, compared with unvaccinated girls, more vaccinated girls believed that contraceptive pills might prevent HPV-related disease (P=0.001). Vaccinated girls better understood the importance of performing regular Pap smears after vaccination (P=0.021). Knowledge on HPV infection and vaccination remains suboptimal, especially among vaccinated teenaged girls, despite a broad information campaign. Misconceptions about the utility of secondary prevention may increase risky sexual behaviors. Copyright © 2013 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Comparison of anamnestic responses to rabies vaccination in dogs and cats with current and out-of-date vaccination status.

PubMed

Moore, Michael C; Davis, Rolan D; Kang, Qing; Vahl, Christopher I; Wallace, Ryan M; Hanlon, Cathleen A; Mosier, Derek A

2015-01-15

To compare anamnestic antibody responses of dogs and cats with current versus out-of-date vaccination status. Cross-sectional study. 74 dogs and 33 cats. Serum samples were obtained from dogs and cats that had been exposed to rabies and brought to a veterinarian for proactive serologic monitoring or that had been brought to a veterinarian for booster rabies vaccination. Blood samples were collected on the day of initial evaluation (day 0) and then again 5 to 15 days later. On day 0, a rabies vaccine was administered according to label recommendations. Paired serum samples were analyzed for antirabies antibodies by means of a rapid fluorescent focus inhibition test. All animals had an antirabies antibody titer ≥ 0.5 IU/mL 5 to 15 days after booster vaccination. Dogs with an out-of-date vaccination status had a higher median increase in titer, higher median fold increase in titer, and higher median titer following booster vaccination, compared with dogs with current vaccination status. Most (26/33) cats, regardless of rabies vaccination status, had a titer ≥ 12 IU/mL 5 to 15 days after booster vaccination. Results indicated that dogs with out-of-date vaccination status were not inferior in their antibody response following booster rabies vaccination, compared with dogs with current vaccination status. Findings supported immediate booster vaccination followed by observation for 45 days of dogs and cats with an out-of-date vaccination status that are exposed to rabies, as is the current practice for dogs and cats with current vaccination status.

Cost-effectiveness analysis of rotavirus vaccination in Argentina.

PubMed

Urueña, Analía; Pippo, Tomás; Betelu, María Sol; Virgilio, Federico; Hernández, Laura; Giglio, Norberto; Gentile, Ángela; Diosque, Máximo; Vizzotti, Carla

2015-05-07

Rotavirus is a leading cause of severe diarrhea in children under 5. In Argentina, the most affected regions are the Northeast and Northwest, where hospitalizations and deaths are more frequent. This study estimated the cost-effectiveness of adding either of the two licensed rotavirus vaccines to the routine immunization schedule. The integrated TRIVAC vaccine cost-effectiveness model from the Pan American Health Organization's ProVac Initiative (Version 2.0) was used to assess health benefits, costs savings, life-years gained (LYGs), DALYs averted, and cost/DALY averted of vaccinating 10 successive cohorts, from the health care system and societal perspectives. Two doses of monovalent (RV1) rotavirus vaccine and three doses of pentavalent (RV5) rotavirus vaccine were each compared to a scenario assuming no vaccination. The price/dose was US$ 7.50 and US$ 5.15 for RV1 and RV5, respectively. We ran both a national and sub-national analysis, discounting all costs and benefits 3% annually. Our base case results were compared to a range of alternative univariate and multivariate scenarios. The number of LYGs was 5962 and 6440 for RV1 and RV5, respectively. The cost/DALY averted when compared to no vaccination from the health care system and societal perspective was: US$ 3870 and US$ 1802 for RV1, and US$ 2414 and US$ 358 for RV5, respectively. Equivalent figures for the Northeast were US$ 1470 and US$ 636 for RV1, and US$ 913 and US$ 80 for RV5. Therefore, rotavirus vaccination was more cost-effective in the Northeast compared to the whole country; and, in the Northwest, health service's costs saved outweighed the cost of introducing the vaccine. Vaccination with either vaccine compared to no vaccination was highly cost-effective based on WHO guidelines and Argentina's 2011 per capita GDP of US$ 9090. Key variables influencing results were vaccine efficacy, annual loss of efficacy, relative coverage of deaths, vaccine price, and discount rate. Compared to no

Influence of initial vaccination with 13-valent pneumococcal conjugate vaccine or 23-valent pneumococcal polysaccharide vaccine on anti-pneumococcal responses following subsequent pneumococcal vaccination in adults 50 years and older.

PubMed

Jackson, Lisa A; Gurtman, Alejandra; van Cleeff, Martin; Frenck, Robert W; Treanor, John; Jansen, Kathrin U; Scott, Daniel A; Emini, Emilio A; Gruber, William C; Schmoele-Thoma, Beate

2013-08-02

Unlike free polysaccharide vaccines, pneumococcal polysaccharide conjugate vaccines (PCVs) induce a T cell-dependent immune response and have the potential to provide an extended duration of protection with repeated vaccinations. This was an extension of a previous study in pneumococcal vaccine-naïve adults aged 50-64 years in which adults 60-64 years of age were given 13-valent PCV (PCV13) or 23-valent pneumococcal polysaccharide vaccine (PPSV23) and adults aged 50-59 were given PCV13. In this follow up study conducted about 4 years later, the 60-64 year olds initially given PCV13 received PCV13 or PPSV23, and those initially given PPSV23 received another PPSV23. All adults aged 50-59 years were re-vaccinated with PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured before and 1 month after vaccination. A second PCV13 given about 4 years after a first vaccination induced OPA titers that were significantly higher than those following the initial vaccination for 7 of 13 serotypes in the older group, and 6 of 13 serotypes in the younger group, and responses to the remaining serotypes were largely non-inferior. In contrast, OPA titers following revaccination with PPSV23 were statistically significantly lower for 9 of the 13 serotypes, and non-inferior for the remaining serotypes, when compared to the responses to the first PPSV23. OPA titers in the older adults who received PPSV23 after initial PCV13 were significantly higher than those following a first PPSV23 for 10 of the 13 serotypes. In adults 50 to 64 years of age, initial vaccination with PCV13 establishes an immune state that results in recall anti-pneumococcal responses upon subsequent vaccination with either conjugated or free polysaccharide vaccine. In contrast, initial vaccination with PPSV23 results in an immune state in which subsequent PPSV23 administration yields generally lower responses compared with the initial responses. Copyright © 2013 The Authors. Published by Elsevier

Vaccine administration decision making: the case of yellow fever vaccine.

PubMed

Lown, Beth A; Chen, Lin H; Wilson, Mary E; Sisson, Emily; Gershman, Mark; Yanni, Emad; Jentes, Emily S; Hochberg, Natasha S; Hamer, Davidson H; Barnett, Elizabeth D

2012-09-01

Providers must counsel travelers to yellow fever (YF)-endemic areas, although risk estimates of disease and vaccine serious adverse events (SAEs) may be imprecise. The impact of risk information and patients' requests for participation in vaccine decisions on providers' recommendations is unknown. Vaccine providers were surveyed regarding decisions for 4 patient scenarios before and after being presented information about risk of YF disease vs vaccine SAEs. Participants' theoretical attitudes were compared with actual responses to scenarios in which patients wanted to share vaccine decisions. Analyses were done by using χ(2) tests with significance level of .05. Forty-six percent of respondents made appropriate initial YF vaccine administration decisions for a pregnant woman, 73% for an immunosuppressed man, and 49% for an 8-month-old infant. After receiving scenario-specific information, 20%, 54%, and 23% of respondents respectively who initially responded incorrectly changed to a more appropriate decision. Thirty-one percent of participants made consistently appropriate decisions. Among participants who made ≥1 incorrect decision, 35.7% made no decision changes after receiving information. In the scenario in which either a decision to withhold or to administer vaccine was acceptable, 19% of respondents refused a patient's request for vaccine. Targeted information is necessary but insufficient to change the process of vaccine administration decision making. Providers need additional education to enable them to apply evidence, overcome cognitive decision-making errors, and involve patients in vaccine decisions.

Efficacy of Influenza Vaccination and Tamiflu® Treatment – Comparative Studies with Eurasian Swine Influenza Viruses in Pigs

PubMed Central

Duerrwald, Ralf; Schlegel, Michael; Bauer, Katja; Vissiennon, Théophile; Wutzler, Peter; Schmidtke, Michaela

2013-01-01

Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebulisation with high doses of influenza virus A/swine/Potsdam/15/1981 (H1N1/1981, heterologous challenge to H1N1 vaccine strain) and A/swine/Bakum/1832/2000 (H1N2/2000, homologous challenge to H1N2 vaccine strain) in two independent trials. In each trial (i) 10 pigs were vaccinated twice with a trivalent vaccine (RESPIPORC® FLU3; 28 and 7 days before infection), (ii) another 10 pigs received 150 mg/day of Tamiflu® for 5 days starting 12 h before infection, and (iii) 12 virus-infected pigs were left unvaccinated and untreated and served as controls. Both viruses replicated efficiently in porcine respiratory organs causing influenza with fever, dyspnoea, and pneumonia. Tamiflu® treatment as well as vaccination prevented clinical signs and significantly reduced virus shedding. Whereas after homologous challenge with H1N2/2000 no infectious virus in lung and hardly any lung inflammation were detected, the virus titre was not and the lung pathology was only partially reduced in H1N1/1981, heterologous challenged pigs. Tamiflu® application did not affect these study parameters. In conclusion, all tested preventive measures provided protection against disease. Vaccination additionally prevented virus replication and histopathological changes in the lung of homologous challenged pigs. PMID:23630601

A Comparative Study on the Lot Release Systems for Vaccines as of 2016.

PubMed

Fujita, Kentaro; Naito, Seishiro; Ochiai, Masaki; Konda, Toshifumi; Kato, Atsushi

2017-09-25

Many countries have already established their own vaccine lot release system that is designed for each country's situation: while the World Health Organization promotes for the convergence of these regulatory systems so that vaccines of assured quality are provided globally. We conducted a questionnaire-based investigation of the lot release systems for vaccines in 7 countries and 2 regions. We found that a review of the summary protocol by the National Regulatory Authorities was commonly applied for the independent lot release of vaccines, however, we also noted some diversity between countries, especially in regard to the testing policy. Some countries and regions, including Japan, regularly tested every lot of vaccines, whereas the frequency of these tests was reduced in other countries and regions as determined based on the risk assessment of these products. Test items selected for the lot release varied among the countries or regions investigated, although there was a tendency to prioritize the potency tests. An understanding of the lot release policy may contribute to improving and harmonizing the lot release system globally in the future.

Anti-Group B Streptococcus Glycan-Conjugate Vaccines Using Pilus Protein GBS80 As Carrier and Antigen: Comparing Lysine and Tyrosine-directed Conjugation.

PubMed

Nilo, Alberto; Morelli, Laura; Passalacqua, Irene; Brogioni, Barbara; Allan, Martin; Carboni, Filippo; Pezzicoli, Alfredo; Zerbini, Francesca; Maione, Domenico; Fabbrini, Monica; Romano, Maria Rosaria; Hu, Qi-Ying; Margarit, Immaculada; Berti, Francesco; Adamo, Roberto

2015-07-17

Gram-positive Streptococcus agalactiae or group B Streptococcus (GBS) is a leading cause of invasive infections in pregnant women, newborns, and elderly people. Vaccination of pregnant women represents the best strategy for prevention of neonatal disease, and GBS polysaccharide-based conjugate vaccines are currently under clinical testing. The potential of GBS pilus proteins selected by genome-based reverse vaccinology as protective antigens for anti-streptococcal vaccines has also been demonstrated. Dressing pilus proteins with surface glycan antigens could be an attractive approach to extend vaccine coverage. We have recently developed an efficient method for tyrosine-directed ligation of large glycans to proteins via copper-free azide-alkyne [3 + 2] cycloaddition. This method enables targeting of predetermined sites of the protein, ensuring that protein epitopes are preserved prior to glycan coupling and a higher consistency in glycoconjugate batches. Herein, we compared conjugates of the GBS type II polysaccharide (PSII) and the GBS80 pilus protein obtained by classic lysine random conjugation and by the recently developed tyrosine-directed ligation. PSII conjugated to CRM197, a carrier protein used for vaccines in the market, was used as a control. We found that the constructs made from PSII and GBS80 were able to elicit murine antibodies recognizing individually the glycan and protein epitopes on the bacterial surface. The generated antibodies were efficacious in mediating opsonophagocytic killing of strains expressing exclusively PSII or GBS80 proteins. The two glycoconjugates were also effective in protecting newborn mice against GBS infection following vaccination of the dams. Altogether, these results demonstrated that polysaccharide-conjugated GBS80 pilus protein functions as a carrier comparably to CRM197, while maintaining its properties of protective protein antigen. Glycoconjugation and reverse vaccinology can, therefore, be combined to design

Recombinant BCG vaccine candidates.

PubMed

Hernàndez-Pando, Rogelio; Castañòn, Mauricio; Espitia, Clara; Lopez-Vidal, Yolanda

2007-06-01

Given the variable protective efficacy provided by Mycobacterium bovis BCG (Bacillus Calmette-Guérin), there is a concerted effort worldwide to develop better vaccines that could be used to reduce the burden of tuberculosis. Recombinant BCG (rBCG) are vaccine candidates that offer some potential in this area. In this paper, we will discuss the molecular methods used to generate rBCG, and the results obtained with some of these new vaccines as compared with the conventional BCG vaccine in diverse animal models. Tuberculosis vaccine candidates based on rBCG are promising candidates, and some of them are now being tested in clinical trials.

Rabies Vaccination: Higher Failure Rates in Imported Dogs than in those Vaccinated in Italy.

PubMed

Rota Nodari, E; Alonso, S; Mancin, M; De Nardi, M; Hudson-Cooke, S; Veggiato, C; Cattoli, G; De Benedictis, P

2017-03-01

The current European Union (EU) legislation decrees that pets entering the EU from a rabies-infected third country have to obtain a satisfactory virus-neutralizing antibody level, while those moving within the EU require only rabies vaccination as the risk of moving a rabid pet within the EU is considered negligible. A number of factors driving individual variations in dog vaccine response have been previously reported, including a high rate of vaccine failure in puppies, especially those subject to commercial transport. A total of 21 001 observations collected from dogs (2006-2012) vaccinated in compliance with the current EU regulations were statistically analysed to assess the effect of different risk factors related to rabies vaccine efficacy. Within this framework, we were able to compare the vaccination failure rate in a group of dogs entering the Italian border from EU and non-EU countries to those vaccinated in Italy prior to international travel. Our analysis identified that cross-breeds and two breed categories showed high vaccine success rates, while Beagles and Boxers were the least likely to show a successful response to vaccination (88.82% and 90.32%, respectively). Our analysis revealed diverse performances among the commercially available vaccines, in terms of serological peak windows, and marked differences according to geographical area. Of note, we found a higher vaccine failure rate in imported dogs (13.15%) than in those vaccinated in Italy (5.89%). Our findings suggest that the choice of vaccine may influence the likelihood of an animal achieving a protective serological level and that time from vaccination to sampling should be considered when interpreting serological results. A higher vaccine failure in imported compared to Italian dogs highlights the key role that border controls still have in assessing the full compliance of pet movements with EU legislation to minimize the risk of rabies being reintroduced into a disease-free area. �

H5N1 influenza vaccine induces a less robust neutralizing antibody response than seasonal trivalent and H7N9 influenza vaccines.

PubMed

Wong, Sook-San; DeBeauchamp, Jennifer; Zanin, Mark; Sun, Yilun; Tang, Li; Webby, Richard

2017-01-01

Conventional inactivated avian influenza vaccines have performed poorly in past vaccine trials, leading to the hypothesis that they are less immunogenic than seasonal influenza vaccines. We tested this hypothesis by comparing the immunogenicity of the H5N1 and H7N9 vaccines (avian influenza vaccines) to a seasonal trivalent inactivated influenza vaccine in naïve ferrets, administered with or without the adjuvants MF59 or AS03. Vaccine immunogenicity was assessed by measuring neutralizing antibody titers against hemagglutinin and neuraminidase and by hemagglutinin -specific IgG levels. Two doses of unadjuvanted vaccines induced low or no HA-specific IgG responses and hemagglutination-inhibiting titers. Adjuvanted vaccines induced comparable IgG-titers, but poorer neutralizing antibody titers for the H5 vaccine. All adjuvanted vaccines elicited detectable anti- neuraminidase -antibodies with the exception of the H5N1 vaccine, likely due to the low amounts of neuraminidase in the vaccine. Overall, the H5N1 vaccine had poorer capacity to induce neutralizing antibodies, but not HA-specific IgG, compared to H7N9 or trivalent inactivated influenza vaccine.

Proteomic profile of culture filtrate from the Brazilian vaccine strain Mycobacterium bovis BCG Moreau compared to M. bovis BCG Pasteur.

PubMed

Berrêdo-Pinho, Marcia; Kalume, Dario E; Correa, Paloma R; Gomes, Leonardo H F; Pereira, Melissa P; da Silva, Renata F; Castello-Branco, Luiz R R; Degrave, Wim M; Mendonça-Lima, Leila

2011-04-20

Bacille Calmette-Guerin (BCG) is currently the only available vaccine against tuberculosis (TB) and comprises a heterogeneous family of sub-strains with genotypic and phenotypic differences. The World Health Organization (WHO) affirms that the characterization of BCG sub-strains, both on genomic and proteomic levels, is crucial for a better comprehension of the vaccine. In addition, these studies can contribute in the development of a more efficient vaccine against TB. Here, we combine two-dimensional electrophoresis (2DE) and mass spectrometry to analyse the proteomic profile of culture filtrate proteins (CFPs) from M. bovis BCG Moreau, the Brazilian vaccine strain, comparing it to that of BCG Pasteur. CFPs are considered of great importance given their dominant immunogenicity and role in pathogenesis, being available for interaction with host cells since early infection. The 2DE proteomic map of M. bovis BCG Moreau CFPs in the pH range 3-8 allowed the identification of 158 spots corresponding to 101 different proteins, identified by MS/MS. Comparison to BCG Pasteur highlights the great similarity between these BCG strains. However, quantitative analysis shows a higher expression of immunogenic proteins such as Rv1860 (BCG1896, Apa), Rv1926c (BCG1965c, Mpb63) and Rv1886c (BCG1923c, Ag85B) in BCG Moreau when compared to BCG Pasteur, while some heat shock proteins, such as Rv0440 (BCG0479, GroEL2) and Rv0350 (BCG0389, DnaK), show the opposite pattern. Here we report the detailed 2DE profile of CFPs from M. bovis BCG Moreau and its comparison to BCG Pasteur, identifying differences that may provide relevant information on vaccine efficacy. These findings contribute to the detailed characterization of the Brazilian vaccine strain against TB, revealing aspects that may lead to a better understanding of the factors leading to BCG's variable protective efficacy against TB.

Atypical antibody responses in dengue vaccine recipients.

PubMed

Kanesa-Thasan, N; Sun, W; Ludwig, G V; Rossi, C; Putnak, J R; Mangiafico, J A; Innis, B L; Edelman, R

2003-12-01

Eight of 69 (12%) healthy adult volunteers vaccinated with monovalent live-attenuated dengue virus (DENV) vaccine candidates had atypical antibody responses, with depressed IgM:IgG antibody ratios and induction of high-titer hemagglutination-inhibiting and neutralizing (NT) antibodies to all four DENV serotypes. These features suggested flavivirus exposure prior to DENV vaccination, yet no volunteer had a history of previous flavivirus infection, flavivirus vaccination, or antibody to flaviviruses evident before DENV vaccination. Moreover, production of antibody to DENV by atypical responders (AR) was not accelerated compared with antibody responses in the 61 flavivirus-naive responders (NR). Further evaluation revealed no differences in sex, age, race, DENV vaccine candidate received, or clinical signs and symptoms following vaccination between AR and NR. However, viremia was delayed at the onset in AR compared with NR. A comparative panel of all AR and five randomly selected NR found flavivirus cross-reactive antibody after vaccination only in AR. Unexpectedly, six of eight AR had NT antibodies to yellow fever virus (YFV) > 1:10 before vaccination while NR had none (P = 0.04). The AR also universally demonstrated YFV NT antibody titers > or = 1:160 after DENV vaccination, whereas four of five NR failed to seroconvert (P = 0.02). Yellow fever virus priming broadens the antibody response to monovalent DENV vaccination. The effect of flavivirus priming on the clinical and immunologic response to tetravalent DENV vaccine remains to be determined.

Ontology-Based Combinatorial Comparative Analysis of Adverse Events Associated with Killed and Live Influenza Vaccines

PubMed Central

Sarntivijai, Sirarat; Xiang, Zuoshuang; Shedden, Kerby A.; Markel, Howard; Omenn, Gilbert S.; Athey, Brian D.; He, Yongqun

2012-01-01

Vaccine adverse events (VAEs) are adverse bodily changes occurring after vaccination. Understanding the adverse event (AE) profiles is a crucial step to identify serious AEs. Two different types of seasonal influenza vaccines have been used on the market: trivalent (killed) inactivated influenza vaccine (TIV) and trivalent live attenuated influenza vaccine (LAIV). Different adverse event profiles induced by these two groups of seasonal influenza vaccines were studied based on the data drawn from the CDC Vaccine Adverse Event Report System (VAERS). Extracted from VAERS were 37,621 AE reports for four TIVs (Afluria, Fluarix, Fluvirin, and Fluzone) and 3,707 AE reports for the only LAIV (FluMist). The AE report data were analyzed by a novel combinatorial, ontology-based detection of AE method (CODAE). CODAE detects AEs using Proportional Reporting Ratio (PRR), Chi-square significance test, and base level filtration, and groups identified AEs by ontology-based hierarchical classification. In total, 48 TIV-enriched and 68 LAIV-enriched AEs were identified (PRR>2, Chi-square score >4, and the number of cases >0.2% of total reports). These AE terms were classified using the Ontology of Adverse Events (OAE), MedDRA, and SNOMED-CT. The OAE method provided better classification results than the two other methods. Thirteen out of 48 TIV-enriched AEs were related to neurological and muscular processing such as paralysis, movement disorders, and muscular weakness. In contrast, 15 out of 68 LAIV-enriched AEs were associated with inflammatory response and respiratory system disorders. There were evidences of two severe adverse events (Guillain-Barre Syndrome and paralysis) present in TIV. Although these severe adverse events were at low incidence rate, they were found to be more significantly enriched in TIV-vaccinated patients than LAIV-vaccinated patients. Therefore, our novel combinatorial bioinformatics analysis discovered that LAIV had lower chance of inducing these two

Low rate of human papillomavirus vaccination among schoolgirls in Lebanon: barriers to vaccination with a focus on mothers’ knowledge about available vaccines

PubMed Central

Abou El-Ola, Maria J; Rajab, Mariam A; Abdallah, Dania I; Fawaz, Ismail A; Awad, Lyn S; Tamim, Hani M; Ibrahim, Ahmad O; Mugharbil, Anas M; Moghnieh, Rima A

2018-01-01

Background Human papillomavirus (HPV) infection is an established predisposing factor of cervical cancer. In this study, we assessed the awareness about genital warts, cervical cancer, and HPV vaccine among mothers having girls who are at the age of primary HPV vaccination attending a group of schools in Lebanon. We also assessed the rate of HPV vaccination among these girls and the barriers to vaccination in this community. Subjects and methods This is a cross-sectional, school-based survey. A 23-item, self-administered, anonymous, pretested, structured questionnaire with closed-ended questions was used to obtain data. The questionnaire was sent to the mothers through their student girls, and they were asked to return it within a week. Data were analyzed using the Statistical Package for Social Sciences version 21.0. Bivariate analysis was performed using the chi-square test to compare categorical variables, whereas continuous variables were compared using the Student’s t-test. Fisher’s exact test was used when chi-square test could not be employed. Results The response rate in our survey was 39.4%. Among the responders, the rate of awareness about HPV infection was 34%, where 72% of the mothers had heard about cervical cancer, and 34% knew that a vaccine is available to prevent cervical cancer. HPV vaccination uptake rate was 2.5%. This lack of vaccination was primarily attributed to the low rate of mothers’ awareness about the vaccine (34%). Factors significantly affecting awareness about the vaccine were the mothers’ marital age, nationality, level of education, employment, and family income. Barriers to HPV vaccination, other than awareness, were uncertainty about safety or efficacy of the vaccine, conservative ideas of mothers regarding their girls’ future sexual life, and relatively high price of the vaccine. Conclusion Vaccine uptake is low among eligible girls attending this group of schools. The barriers to vaccination are multiple; the most

Cost-effectiveness of different human papillomavirus vaccines in Singapore.

PubMed

Lee, Vernon J; Tay, Sun Kuie; Teoh, Yee Leong; Tok, Mei Yin

2011-03-31

Human papillomavirus (HPV) vaccines are widely available and there have been studies exploring their potential clinical impact and cost-effectiveness. However, few studies have compared the cost-effectiveness among the 2 main vaccines available - a bivalent vaccine against HPV 16/18, and a quadrivalent vaccine against 6/11/16/18. We explore the cost-effectiveness of these two HPV vaccines in tropical Singapore. We developed a Markov state-transition model to represent the natural history of cervical cancer to predict HPV infection, cancer incidence, mortality, and costs. Cytologic screening and treatment of different outcomes of HPV infection were incorporated. Vaccination was provided to a cohort of 12-year old females in Singapore, followed up until death. Based on available vaccines on the market, the bivalent vaccine had increased effectiveness against a wider range of HPV types, while the quadrivalent vaccine had effectiveness against genital warts. Incremental cost-effectiveness ratios (ICER) compared vaccination to no-vaccination, and between the two vaccines. Sensitivity analyses explored differences in vaccine effectiveness and uptake, and other key input parameters. For the no vaccination scenario, 229 cervical cancer cases occurred over the cohort's lifetime. The total discounted cost per individual due to HPV infection was SGD$275 with 28.54 discounted life-years. With 100% vaccine coverage, the quadrivalent vaccine reduced cancers by 176, and had an ICER of SGD$12,866 per life-year saved. For the bivalent vaccine, 197 cancers were prevented with an ICER of $12,827 per life-year saved. Comparing the bivalent to the quadrivalent vaccine, the ICER was $12,488 per life-year saved. However, the cost per QALY saved for the quadrivalent vaccine compared to no vaccine was $9,071, while it was $10,392 for the bivalent vaccine, with the quadrivalent vaccine dominating the bivalent vaccine due to the additional QALY effect from reduction in genital warts. The

Randomized Trial to Compare the Immunogenicity and Safety of a CRM or TT Conjugated Quadrivalent Meningococcal Vaccine in Teenagers who Received a CRM or TT Conjugated Serogroup C Vaccine at Preschool Age.

PubMed

Ishola, David A; Andrews, Nick; Waight, Pauline; Yung, Chee-Fu; Southern, Jo; Bai, Xilian; Findlow, Helen; Matheson, Mary; England, Anna; Hallis, Bassam; Findlow, Jamie; Borrow, Ray; Miller, Elizabeth

2015-08-01

Protection after meningococcal C (MenC) conjugate (MCC) vaccination in early childhood is short-lived. Boosting with a quadrivalent vaccine in teenage years, a high-risk period for MenC disease, should protect against additional serogroups but might compromise MenC response. The carrier protein in the primary MCC vaccine determines the response to MCC booster in toddlers, but the relationship between primary vaccine and booster given later is unclear. This study compared responses to a CRM-conjugated or tetanus toxoid (TT)-conjugated MenACWY vaccine in teenagers primed with different MCC vaccines at preschool age. Ninety-three teenagers (16-19 years), who were previously randomized at age 3-6 years to receive single-dose MCC-CRM or MCC-TT, were randomized to receive either MenACWY-CRM or MenACWY-TT booster. Serum bactericidal antibodies (SBA, protective titer ≥ 8) were measured before, 1 month and 6 or 9 months after boosting. Preboosting, MCC-TT-primed teenagers had significantly higher MenC SBA titers than those MCC-CRM-primed (P = 0.02). Postboosting, both MenACWY vaccines induced protective SBA titers to all 4 serogroups in most participants (≥ 98% at 1 month and ≥ 90% by 9 months postboost). The highest MenC SBA titers were seen in those MCC-TT-primed and MenACWY-TT-boosted [geometric mean titer (GMT) ~ 22,000] followed by those boosted with MenACWY-CRM irrespective of priming (GMT ~ 12,000) and then those MCC-CRM-primed and MenACWY-TT-boosted (GMT ~ 5500). The estimated postbooster MenC SBA decline beyond 1 month was ~40% as time since booster doubles. Both vaccines were well tolerated with no attributable serious adverse events. Both MenACWY vaccines safely induced protective sustained antibody responses against all targeted serogroups in MCC-primed teenagers.

Perceptions matter: beliefs about influenza vaccine and vaccination behavior among elderly white, black and Hispanic Americans.

PubMed

Wooten, Karen G; Wortley, Pascale M; Singleton, James A; Euler, Gary L

2012-11-06

Knowledge and beliefs about influenza vaccine that differ across racial or ethnic groups may promote racial or ethnic disparities in vaccination. To identify associations between vaccination behavior and personal beliefs about influenza vaccine by race or ethnicity and education levels among the U.S. elderly population. Data from a national telephone survey conducted in 2004 were used for this study. Responses for 3875 adults ≥ 65 years of age were analyzed using logistic regression methods. Racial and ethnic differences in beliefs were observed. For example, whites were more likely to believe influenza vaccine is very effective in preventing influenza compared to blacks and Hispanics (whites, 60%; blacks, 47%, and Hispanics, 51%, p<0.01). Among adults who believed the vaccine is very effective, self-reported vaccination was substantially higher across all racial/ethnic groups (whites, 93%; blacks, 76%; Hispanics, 78%) compared to adults who believed the vaccine was only somewhat effective (whites 67%; blacks 61%, Hispanics 61%). Also, vaccination coverage differed by education level and personal beliefs of whites, blacks, and Hispanics. Knowledge and beliefs about influenza vaccine may be important determinants of influenza vaccination among racial/ethnic groups. Strategies to increase coverage should highlight the burden of influenza disease in racial and ethnic populations, the benefits and safety of vaccinations and personal vulnerability to influenza disease if not vaccinated. For greater effectiveness, factors associated with the education levels of some communities may need to be considered when developing or implementing new strategies that target specific racial or ethnic groups. Published by Elsevier Ltd.

Onset of immunity in kittens after vaccination with a non-adjuvanted vaccine against feline panleucopenia, feline calicivirus and feline herpesvirus.

PubMed

Jas, D; Aeberlé, C; Lacombe, V; Guiot, A L; Poulet, H

2009-10-01

The induction of a quick onset of immunity against feline parvovirus (FPV), feline herpesvirus (FHV) and feline calicivirus (FCV) is critical both in young kittens after the decline of maternal antibodies and in cats at high risk of exposure. The onset of immunity for the core components was evaluated in 8-9 week old specific pathogen free kittens by challenge 1 week after vaccination with a combined modified live (FPV, FHV) and inactivated (FCV) vaccine. The protection obtained 1 week after vaccination was compared to that obtained when the challenge was performed 3-4 weeks after vaccination. The protocol consisted of a single injection for vaccination against FPV and two injections 4 weeks apart for FHV and FCV. At 1 week after vaccination, the kittens showed no FPV-induced clinical signs or leukopenia following challenge, and after FCV and FHV challenges the clinical score was significantly lower in vaccinated animals than in controls. Interestingly, the relative efficacy of the vaccination was comparable whether the animals were challenged 1 week or 3-4 weeks after vaccination, indicating that the onset of protection occurred within 7 days of vaccination. Following the 1-week challenge, excretion of FPV, FHV and FCV was significantly reduced in vaccinated cats compared to control kittens, confirming the onset of immunity within 7 days of vaccination.

Identification of IBV QX vaccine markers : Should vaccine acceptance by authorities require similar identifications for all live IBV vaccines?

PubMed

Listorti, Valeria; Laconi, Andrea; Catelli, Elena; Cecchinato, Mattia; Lupini, Caterina; Naylor, Clive J

2017-10-09

IBV genotype QX causes sufficient disease in Europe for several commercial companies to have started developing live attenuated vaccines. Here, one of those vaccines (L1148) was fully consensus sequenced alongside its progenitor field strain (1148-A) to determine vaccine markers, thereby enabling detection on farms. Twenty-eight single nucleotide substitutions were associated with the 1148-A attenuation, of which any combination can identify vaccine L1148 in the field. Sixteen substitutions resulted in amino acid coding changes of which half were in spike. One change in the 1b gene altered the normally highly conserved final 5 nucleotides of the transcription regulatory sequence of the S gene, common to all IBV QX genes. No mutations can currently be associated with the attenuation process. Field vaccination strategies would greatly benefit by such comparative sequence data being mandatorily submitted to regulators prior to vaccine release following a successful registration process. Copyright © 2017. Published by Elsevier Ltd.

Modified live infectious bursal disease virus (IBDV) vaccine delays infection of neonatal broiler chickens with variant IBDV compared to turkey herpesvirus (HVT)-IBDV vectored vaccine.

PubMed

Kurukulasuriya, Shanika; Ahmed, Khawaja Ashfaque; Ojkic, Davor; Gunawardana, Thushari; Goonewardene, Kalhari; Gupta, Ashish; Chow-Lockerbie, Betty; Popowich, Shelly; Willson, Philip; Tikoo, Suresh K; Gomis, Susantha

2017-02-07

Chickens are commonly processed around 35-45days of age in broiler chicken industry hence; diseases that occur at a young age are of paramount economic importance. Early age infection with infectious bursal disease virus (IBDV) results in long-lasting immunosuppression and profound economic losses. To our knowledge, this is the first study comparing the protection efficacy of modified live (MdLV) IBDV and herpesvirus turkey (HVT)-IBDV vaccines against early age variant IBDV (varIBDV) infection in chicks. Experiments were carried out in IBDV maternal antibody (MtAb) positive chicks (n=330), divided into 6 groups (n=50-60/group), namely Group 1 (saline), Group 2 (saline+varIBDV), Group 3 (HVT-IBDV), Group 4 (HVT-IBDV+varIBDV), Group 5 (MdLV) and Group 6 (MdLV+varIBDV). HVT-IBDV vaccination was given via the in ovo route to 18-day-old embryonated eggs. MdLV was administered via the subcutaneous route in day-old broilers. Group 2, Group 4 and Group 6 were orally challenged with varIBDV (SK-09, 3×10 3 EID 50 ) at day 6 post-hatch. IBDV seroconversion, bursal weight to body weight ratio (BBW) and bursal histopathology were assessed at 19 and 35days of age. Histopathological examination at day 19 revealed that varIBDV-SK09 challenge caused severe bursal atrophy and lower BBW in HVT-IBDV but not in MdLV vaccinated chicks. However by day 35, all challenged groups showed bursal atrophy and seroconversion. Interestingly, RT-qPCR analysis after varIBDV-SK09 challenge demonstrated an early (9days of age) and significantly high viral load (∼5744 folds) in HVT-IBDV vaccinated group vs unvaccinated challenged group (∼2.25 folds). Furthermore, flow cytometry analysis revealed inhibition of cytotoxic CD8 + T-cell response (CD44-downregulation) and decreased splenic lymphocytes counts in chicks after HVT-IBDV vaccination. Overall, our data suggest that MdLV delays varIBDV pathogenesis, whereas, HVT-IBDV vaccine is potentially immunosuppressive, which may increase the risk of

Exploring and Promoting Prosocial Vaccination: A Cross-Cultural Experiment on Vaccination of Health Care Personnel

PubMed Central

Betsch, Cornelia; Korn, Lars; Holtmann, Cindy

2016-01-01

Influenza vaccination for health care personnel (HCP) is recommended particularly because it indirectly protects patients from contracting the disease. Vaccinating can therefore be interpreted as a prosocial act. However, HCP vaccination rates are often far too low to prevent nosocomial infections. Effective interventions are needed to increase HCP's influenza vaccine uptake. Here we devise a novel tool to experimentally test interventions that aim at increasing prosocially motivated vaccine uptake under controlled conditions. We conducted a large-scale and cross-cultural experiment with participants from countries with either a collectivistic (South Korea) or an individualistic (USA) cultural background. Results showed that prosocially motivated vaccination was more likely in South Korea compared to the US, mediated by a greater perception of vaccination as a social act. However, changing the default of vaccination, such that participants had to opt out rather than to opt in, increased vaccine uptake in the US and therefore compensated for the lower level of prosocial vaccination. In sum, the present study provides both a novel method to investigate HCP influenza vaccination behavior and interventions to increase their vaccine uptake. PMID:27725940

Exploring and Promoting Prosocial Vaccination: A Cross-Cultural Experiment on Vaccination of Health Care Personnel.

PubMed

Böhm, Robert; Betsch, Cornelia; Korn, Lars; Holtmann, Cindy

2016-01-01

Influenza vaccination for health care personnel (HCP) is recommended particularly because it indirectly protects patients from contracting the disease. Vaccinating can therefore be interpreted as a prosocial act. However, HCP vaccination rates are often far too low to prevent nosocomial infections. Effective interventions are needed to increase HCP's influenza vaccine uptake. Here we devise a novel tool to experimentally test interventions that aim at increasing prosocially motivated vaccine uptake under controlled conditions. We conducted a large-scale and cross-cultural experiment with participants from countries with either a collectivistic (South Korea) or an individualistic (USA) cultural background. Results showed that prosocially motivated vaccination was more likely in South Korea compared to the US, mediated by a greater perception of vaccination as a social act. However, changing the default of vaccination, such that participants had to opt out rather than to opt in, increased vaccine uptake in the US and therefore compensated for the lower level of prosocial vaccination. In sum, the present study provides both a novel method to investigate HCP influenza vaccination behavior and interventions to increase their vaccine uptake.

Description and molecular phylogeny of a new species of Phoronis (Phoronida) from Japan, with a redescription of topotypes of P. ijimai Oka, 1897

PubMed Central

Hirose, Masato; Fukiage, Ryuma; Katoh, Toru; Kajihara, Hiroshi

2014-01-01

Abstract We describe Phoronis emigi sp. n. as the eighth member of the genus based on specimens collected from a sandy bottom at 33.2 m depth in Tomioka Bay, Amakusa, Japan. The new species is morphologically similar to P. psammophila Cori, 1889, but can be distinguished from the latter by the number of longitudinal muscle bundles in the body wall (56–72 vs. 25–50 in P. psammophila) and the position of the nephridiopores (situated level with the anus vs. lower than the anus in P. psammophila). Using sequences of the nuclear 18S and 28S rRNA genes and the mitochondrial cytochrome c oxidase subunit I (COI) gene, we inferred the relationship of P. emigi to other phoronids by the maximum likelihood method and Bayesian analysis. The analyses showed that P. emigi is closely related to P. hippocrepia Wright, 1856 and P. psammophila Cori, 1889. We describe the morphology of the topotypes and additional material for P. ijimai Oka, 1897. Neither our morphological observations of P. ijimai, nor the phylogenetic analyses based on 18S and COI sequences, contradicts that P. vancouverensis Pixell, 1912 is conspecific with P. ijimai, a synonymy that has long been disputed. PMID:24715799

Whooping crane titers to eastern equine encephalitis vaccinations

USGS Publications Warehouse

Olsen, Glenn H.; Kolski, E.; Hatfield, J.S.; Docherty, D.E.; Chavez-Ramirez, Felipe

2005-01-01

In 1984 an epizootic of eastern equine encephalitis (EEE) virus killed 7 of 39 (18%) whooping cranes in captivity at the Patuxent Wildlife Research Center in Laurel, Maryland, USA. Since that time whooping cranes have been vaccinated with a human EEE vaccine. This vaccine was unavailable for several years, necessitating use of an equine vaccine in the cranes. This study compared the antibody titers measured for three years using the human vaccine with those measured for two years using the equine form. Whooping cranes developed similarly elevated titers in one year using the human vaccine and both years using the equine vaccine. However, in two years where the human vaccine was used, the whooping cranes developed significantly lower titers compared to other years.

Efficacy of vaccination with La Sota strain vaccine to control Newcastle disease in village chickens in Nepal.

PubMed

Shrestha, Sulochana; Dhawan, Mamta; Donadeu, Meritxell; Dungu, Baptiste

2017-02-01

The efficacy of vaccination with Newcastle disease (ND) La Sota and R 2 B (Mukteswar) modified live strain vaccines was determined by experimental challenge and with ND La Sota vaccine under field conditions in Nepal. Booster vaccination with ND La Sota vaccine after a primary vaccination with ND La Sota vaccine, induced a geometric mean titre (GMT) of 5.0 log 2 haemagglutination inhibition (HI) units, compared to a GMT of 6.0 log 2 HI units following booster vaccination with R 2 B vaccine 1 month after primary vaccination with ND La Sota vaccine. Both vaccines provided 100% protection against challenge with a local field ND strain. Furthermore, booster vaccination with ND La Sota vaccine induced protective levels of antibody after field use in villages in Jhapa, and no outbreaks of ND occurred during the study period. The ND La Sota modified live vaccine is immunogenic and efficacious and is a suitable vaccine for use in vaccination programmes in village chickens in the rural areas of Nepal.

HPV vaccination prevalence, parental barriers and motivators to vaccinating children in Hawai'i.

PubMed

Dela Cruz, May Rose Isnec; Braun, Kathryn L; Tsark, Jo Ann Umilani; Albright, Cheryl Lynn; Chen, John J

2018-05-10

To determine the prevalence and barriers to human papillomavirus (HPV) vaccine uptake among 11-18 year olds in the Hawai'i's four major ethnic groups-Native Hawaiians, Filipinos, Japanese, and Caucasians. A telephone survey assessed parents' knowledge of HPV and the HPV vaccine, status of their child's HPV vaccine uptake, variables operationalizing the Health Belief Model, and barriers and motivators to uptake. Across the groups, 799 parents completed the survey. About 35% of daughters and 19% of sons had received all three shots. Although ethnic differences in vaccine uptake were seen in bivariate analysis (with significantly lower uptake in Filipino youth), in multivariable logistic regression analysis, only Caucasian parents were significantly less likely to start their sons on the HPV vaccine series compared with Japanese parents (reference group). Having heard about the vaccine, believing in its effectiveness, and older age of the child were also associated with vaccine uptake. Motivators for HPV vaccination were physician's recommendation and wanting to protect one's child. The primary barrier to uptake was lack of knowledge about the vaccine. Findings reinforce the fact that a physician's recommendation and receipt of information about the vaccine are strong motivators for parents to vaccinate their children, regardless of ethnicity.

Respiratory and oral vaccination improves protection conferred by the live vaccine strain against pneumonic tularemia in the rabbit model

PubMed Central

Stinson, Elizabeth; Smith, Le'Kneitah P.; Cole, Kelly Stefano; Barry, Eileen M.; Reed, Douglas S.

2016-01-01

Tularemia is a severe, zoonotic disease caused by a gram-negative bacterium, Francisella tularensis. We have previously shown that rabbits are a good model of human pneumonic tularemia when exposed to aerosols containing a virulent, type A strain, SCHU S4. We further demonstrated that the live vaccine strain (LVS), an attenuated type B strain, extended time to death when given by scarification. Oral or aerosol vaccination has been previously shown in humans to offer superior protection to parenteral vaccination against respiratory tularemia challenge. Both oral and aerosol vaccination with LVS were well tolerated in the rabbit with only minimal fever and no weight loss after inoculation. Plasma antibody titers against F. tularensis were higher in rabbits that were vaccinated by either oral or aerosol routes compared to scarification. Thirty days after vaccination, all rabbits were challenged with aerosolized SCHU S4. LVS given by scarification extended time to death compared to mock-vaccinated controls. One orally vaccinated rabbit did survive aerosol challenge, however, only aerosol vaccination extended time to death significantly compared to scarification. These results further demonstrate the utility of the rabbit model of pneumonic tularemia in replicating what has been reported in humans and macaques as well as demonstrating the utility of vaccination by oral and respiratory routes against an aerosol tularemia challenge. PMID:27511964

Respiratory and oral vaccination improves protection conferred by the live vaccine strain against pneumonic tularemia in the rabbit model.

PubMed

Stinson, Elizabeth; Smith, Le'Kneitah P; Cole, Kelly Stefano; Barry, Eileen M; Reed, Douglas S

2016-10-01

Tularemia is a severe, zoonotic disease caused by a gram-negative bacterium, Francisella tularensis We have previously shown that rabbits are a good model of human pneumonic tularemia when exposed to aerosols containing a virulent, type A strain, SCHU S4. We further demonstrated that the live vaccine strain (LVS), an attenuated type B strain, extended time to death when given by scarification. Oral or aerosol vaccination has been previously shown in humans to offer superior protection to parenteral vaccination against respiratory tularemia challenge. Both oral and aerosol vaccination with LVS were well tolerated in the rabbit with only minimal fever and no weight loss after inoculation. Plasma antibody titers against F. tularensis were higher in rabbits that were vaccinated by either oral or aerosol routes compared to scarification. Thirty days after vaccination, all rabbits were challenged with aerosolized SCHU S4. LVS given by scarification extended time to death compared to mock-vaccinated controls. One orally vaccinated rabbit did survive aerosol challenge, however, only aerosol vaccination extended time to death significantly compared to scarification. These results further demonstrate the utility of the rabbit model of pneumonic tularemia in replicating what has been reported in humans and macaques as well as demonstrating the utility of vaccination by oral and respiratory routes against an aerosol tularemia challenge. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Influenza vaccine-mediated protection in older adults: Impact of influenza infection, cytomegalovirus serostatus and vaccine dosage.

PubMed

Merani, Shahzma; Kuchel, George A; Kleppinger, Alison; McElhaney, Janet E

2018-07-01

Age-related changes in T-cell function are associated with a loss of influenza vaccine efficacy in older adults. Both antibody and cell-mediated immunity plays a prominent role in protecting older adults, particularly against the serious complications of influenza. High dose (HD) influenza vaccines induce higher antibody titers in older adults compared to standard dose (SD) vaccines, yet its impact on T-cell memory is not clear. The aim of this study was to compare the antibody and T-cell responses in older adults randomized to receive HD or SD influenza vaccine as well as determine whether cytomegalovirus (CMV) serostatus affects the response to vaccination, and identify differences in the response to vaccination in those older adults who subsequently have an influenza infection. Older adults (≥65years) were enrolled (n=106) and randomized to receive SD or HD influenza vaccine. Blood was collected pre-vaccination, followed by 4, 10 and 20weeks post-vaccination. Serum antibody titers, as well as levels of inducible granzyme B (iGrB) and cytokines were measured in PBMCs challenged ex vivo with live influenza virus. Surveillance conducted during the influenza season identified those with laboratory confirmed influenza illness or infection. HD influenza vaccination induced a high antibody titer and IL-10 response, and a short-lived increase in Th1 responses (IFN-γ and iGrB) compared to SD vaccination in PBMCs challenged ex vivo with live influenza virus. Of the older adults who became infected with influenza, a high IL-10 and iGrB response in virus-challenged cells was observed post-infection (week 10 to 20), as well as IFN-γ and TNF-α at week 20. Additionally, CMV seropositive older adults had an impaired iGrB response to influenza virus-challenge, regardless of vaccine dose. This study illustrates that HD influenza vaccines have little impact on the development of functional T-cell memory in older adults. Furthermore, poor outcomes of influenza infection in

Experience with live rubella virus vaccine combined with live vaccines against measles and mumps*

PubMed Central

Smorodintsev, A. A.; Nasibov, M. N.; Jakovleva, N. V.

1970-01-01

Vaccination of pre-school children in the 1-7-years age-group for the specific prophylaxis of mumps and rubella is often difficult to arrange because of the already large number of inoculations given to these children. Combined vaccines to protect against measles, mumps and rubella should therefore be a valuable development. The existence of effective live vaccines for each of these 3 diseases makes possible the production of a single preparation suitable for subcutaneous inoculation. Tests on vaccine strains of measles (Leningrad-16), mumps (Leningrad-3) and rubella (Leningrad-8) viruses in various combinations have established that divalent or trivalent vaccines remain clinically harmless, highly immunogenic and epidemiologically effective. Single subcutaneous administrations of live measles vaccine combined with mumps or rubella vaccines or both, when given to children aged 1-8 years, brough about a high percentage of serological conversions and an increase in antibodies to a level comparable with that achieved with the corresponding monovalent vaccines. Morbidity from the 3 diseases was reduced among those vaccinated with the trivalent vaccine by 10 or more times, i.e., by about the same factor as when monovalent or divalent vaccines were used. PMID:5310140

Pricing of new vaccines

PubMed Central

McGlone, Sarah M

2010-01-01

New vaccine pricing is a complicated process that could have substantial long-standing scientific, medical and public health ramifications. Pricing can have a considerable impact on new vaccine adoption and, thereby, either culminate or thwart years of research and development and public health efforts. Typically, pricing strategy consists of the following eleven components: (1) Conduct a target population analysis; (2) Map potential competitors and alternatives; (3) Construct a vaccine target product profile (TPP) and compare it to projected or actual TPPs of competing vaccines; (4) Quantify the incremental value of the new vaccine's characteristics; (5) Determine vaccine positioning in the marketplace; (6) Estimate the vaccine price-demand curve; (7) Calculate vaccine costs (including those of manufacturing, distribution, and research and development); (8) Account for various legal, regulatory, third party payer and competitor factors; (9) Consider the overall product portfolio; (10) Set pricing objectives; (11) Select pricing and pricing structure. While the biomedical literature contains some studies that have addressed these components, there is still considerable room for more extensive evaluation of this important area. PMID:20861678

Pricing of new vaccines.

PubMed

Lee, Bruce Y; McGlone, Sarah M

2010-08-01

New vaccine pricing is a complicated process that could have substantial long-standing scientific, medical, and public health ramifications. Pricing can have a considerable impact on new vaccine adoption and, thereby, either culminate or thwart years of research and development and public health efforts. Typically, pricing strategy consists of the following ten components: 1. Conduct a target population analysis; 2. Map potential competitors and alternatives; 3. Construct a vaccine target product profile (TPP) and compare it to projected or actual TPPs of competing vaccines; 4. Quantify the incremental value of the new vaccine's characteristics; 5. Determine vaccine positioning in the marketplace; 6. Estimate the vaccine price-demand curve; 7. Calculate vaccine costs (including those of manufacturing, distribution, and research and development); 8. Account for various legal, regulatory, third party payer, and competitor factors; 9. Consider the overall product portfolio; 10. Set pricing objectives; 11. Select pricing and pricing structure. While the biomedical literature contains some studies that have addressed these components, there is still considerable room for more extensive evaluation of this important area.

A study of vaccine-induced immune pressure on breakthrough infections in the Phambili phase 2b HIV-1 vaccine efficacy trial

PubMed Central

Rolland, M.; Magaret, C.A.; Rademeyer, C.; Fiore-Gartland, A.; Edlefsen, P.T.; DeCamp, A.; Ahmed, H.; Ngandu, N.; Larsen, B.B.; Frahm, N.; Marais, J.; Thebus, R.; Geraghty, D.; Hural, J.; Corey, L.; Kublin, J.; Gray, G.; McElrath, M.J.; Mullins, J.I.; Gilbert, P.B.; Williamson, C.

2016-01-01

Introduction The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic. Materials and methods A sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients. Vaccine coverage was estimated by computing the percentage of 9-mers that were exact matches to the vaccine insert. Results There was significantly greater protein distances from the vaccine immunogen sequence in Gag (p = 0.045) and Nef (p = 0.021) in viruses infecting vaccine recipients compared to placebo recipients. Twenty-seven putative sites of vaccine-induced pressure were identified (p < 0.05) in Gag (n = 10), Pol (n = 7) and Nef (n = 10), although they did not remain significant after adjustment for multiple comparisons. We found the epitope sieve effect in Step was driven by HLA A*02:01; an allele which was found in low frequency in Phambili participants compared to Step participants. Furthermore, the coverage of the vaccine against subtype C Phambili viruses was 31%, 46% and 14% for Gag, Pol and Nef, respectively, compared to subtype B Step virus coverage of 56%, 61% and 26%, respectively. Discussion This study presents evidence of sieve effects in Gag and Nef; however could not confirm effects on specific amino acid sites. We propose that this weaker signal of vaccine immune pressure detected in the Phambili study compared to the Step study may have been influenced by differences in host genetics (HLA allele frequency) and reduced impact of vaccine-induced immune responses due to mismatch between the viral subtype in the vaccine and infecting subtypes. PMID:27756485

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine compared with two trivalent inactivated influenza vaccines containing alternate B strains in adults: A phase 3, randomized noninferiority study.

PubMed

Treanor, John T; Albano, Frank R; Sawlwin, Daphne C; Graves Jones, Alison; Airey, Jolanta; Formica, Neil; Matassa, Vince; Leong, Jane

2017-04-04

Vaccination is the most effective means of influenza prevention. Efficacy of trivalent vaccines may be enhanced by including both B strain lineages. This phase 3, double-blind study assessed the immunogenicity and safety/tolerability of a quadrivalent inactivated influenza vaccine (IIV4) versus the United States (US)-licensed 2014-2015 trivalent inactivated influenza vaccine (IIV3-Yamagata [IIV3-YAM]; Afluria) and IIV3 containing the alternate Victoria B strain (IIV3-VIC) in adults ≥18years. Participants (n=3484) were randomized 2:1:1 and stratified by age to receive IIV4 (n=1741), IIV3-YAM (n=871), or IIV3-VIC (n=872). The primary objective was to demonstrate noninferiority of the immunological response to IIV4 versus IIV3-YAM and IIV3-VIC. Noninferiority was assessed by hemagglutination inhibition geometric mean titer (GMT) ratio (IIV3/IIV4; upper bound of two-sided 95% confidence interval [CI]≤1.5) and seroconversion rate (SCR) difference (IIV3 - IIV4; upper bound of two-sided 95% CI≤10%) for vaccine strains. Solicited local and systemic adverse events (AEs) were assessed for 7days postvaccination, AEs recorded for 28days postvaccination, and serious AEs for 6months postvaccination. IIV4 elicited a noninferior immune response for matched strains, and superior response for unmatched B strains not contained in IIV3 comparators. Adjusted GMT ratios (95% CI) for A/H1N1, A/H3N2, B/YAM, and B/VIC strains were 0.93 (0.88, 0.99), 0.93 (0.88, 0.98), 0.87 (IIV3-YAM; 0.82, 0.93), and 0.95 (IIV3-VIC; 0.88, 1.03), respectively. Corresponding values for SCR differences (95% CI) were -1.1 (-4.5, 2.3), -1.7 (-5.0, 1.7), -3.2 (IIV3-YAM; -7.4, 0.9), and -1.6 (IIV3-VIC; -5.8, 2.5). AEs were generally mild and experienced by 52.9% of participants. Serious AEs were reported with a slightly higher frequency with IIV4 (2.3%) versus IIV3-YAM (1.6%) and IIV3-VIC (1.5%). IIV4 demonstrated immunological noninferiority to the US-licensed IIV3, and superiority for unmatched B strains

Comparative performance of public and private sector delivery of BCG vaccination: evidence from Sub-Saharan Africa.

PubMed

Wagner, Zachary; Szilagyi, Peter G; Sood, Neeraj

2014-07-31

The private sector is an important source of health care in the developing world. However, there is limited evidence on how private providers compare to public providers, particularly for preventive services such as immunizations. We used data from Sub-Saharan Africa (SSA) to assess public-private differences in Bacillus Calmette-Guérin (BCG) vaccine delivery. We used demographic and health surveys from 102,629 children aged 0-59 months from 29 countries across SSA to measure differences in BCG status for children born at private versus public health facilities (BCG is recommended at birth). We used a probit model to estimate public-private differences in BCG delivery, while controlling for key confounders. Next, we estimated how differences in BCG status evolved over time for children born at private versus public facilities. Finally, we estimated heterogeneity in public-private differences based on wealth and rural-urban residency. We found that children born at a private facility were 7.1 percentage points less likely to receive BCG vaccine in the same month as birth than children born at a public facility (95% CI 6.3-8.0; p<0.001). Most of this difference was driven by for-profit private providers (as opposed to NGOs) where the BCG provision rate was 10.0 percentage points less than public providers (95% CI 9.0-11.2; p<0.001) compared to only 2.4 percentage points for NGOs (95% CI 1.0-3. 8; p<0.01). Moreover, children born at private for-profit facilities remained less likely to be vaccinated up to 59 months after birth. Finally, public-private differences were more pronounced for poorer children and children in rural areas. The for-profit private sector performed substantially worse than the public sector in providing BCG vaccine to newborns, resulting in a longer duration of vulnerability to tuberculosis. This disparity was greater for poorer children and children in rural areas. Copyright © 2014 Elsevier Ltd. All rights reserved.

Veterinary and human vaccine evaluation methods

PubMed Central

Knight-Jones, T. J. D.; Edmond, K.; Gubbins, S.; Paton, D. J.

2014-01-01

Despite the universal importance of vaccines, approaches to human and veterinary vaccine evaluation differ markedly. For human vaccines, vaccine efficacy is the proportion of vaccinated individuals protected by the vaccine against a defined outcome under ideal conditions, whereas for veterinary vaccines the term is used for a range of measures of vaccine protection. The evaluation of vaccine effectiveness, vaccine protection assessed under routine programme conditions, is largely limited to human vaccines. Challenge studies under controlled conditions and sero-conversion studies are widely used when evaluating veterinary vaccines, whereas human vaccines are generally evaluated in terms of protection against natural challenge assessed in trials or post-marketing observational studies. Although challenge studies provide a standardized platform on which to compare different vaccines, they do not capture the variation that occurs under field conditions. Field studies of vaccine effectiveness are needed to assess the performance of a vaccination programme. However, if vaccination is performed without central co-ordination, as is often the case for veterinary vaccines, evaluation will be limited. This paper reviews approaches to veterinary vaccine evaluation in comparison to evaluation methods used for human vaccines. Foot-and-mouth disease has been used to illustrate the veterinary approach. Recommendations are made for standardization of terminology and for rigorous evaluation of veterinary vaccines. PMID:24741009

Making Vaccine Messaging Stick: Perceived Causal Instability as a Barrier to Effective Vaccine Messaging.

PubMed

Dixon, Graham N

2017-08-01

Health officials often face challenges in communicating the risks associated with not vaccinating, where persuasive messages can fail to elicit desired responses. However, the mechanisms behind these failures have not been fully ascertained. To address this gap, an experiment (N = 163) tested the differences between loss-framed messages-one emphasizing the consequence of not receiving a flu vaccine; the other emphasizing the consequence of receiving the flu vaccine. Despite an identical consequence (i.e., Guillain-Barre syndrome), the message highlighting the consequence of not receiving the flu vaccine produced lower negative affect scores as compared to the message highlighting the consequence of receiving the flu vaccine. Mediation analyses suggest that one reason for this difference is due to non-vaccination being perceived as temporary and reversible, whereas vaccination is perceived as being permanent. Implications on health communication and future research are discussed.

Oral delivery of BCG Moreau Rio de Janeiro gives equivalent protection against tuberculosis but with reduced pathology compared to parenteral BCG Danish vaccination.

PubMed

Clark, Simon O; Kelly, Dominic L F; Badell, Edgar; Castello-Branco, Luiz Roberto; Aldwell, Frank; Winter, Nathalie; Lewis, David J M; Marsh, Philip D

2010-10-08

There is a need for an improved vaccine to better control human tuberculosis (TB), as the only currently available TB vaccine, bacillus Calmette-Guerin (BCG) delivered parenterally, offers variable levels of efficacy. Therefore, recombinant strains expressing additional antigens are being developed alongside alternative routes to parenteral delivery. There is strong evidence that BCG Moreau (RdJ) is a safe and effective vaccine in humans when given by the oral route. This study compared the efficacy of a single oral dose of wild type BCG Moreau Rio de Janeiro (RdJ), or a recombinant RdJ strain expressing Ag85B-ESAT6 fusion protein, formulated with and without lipid to enhance oral delivery, with subcutaneous BCG Danish 1331 and saline control groups in a guinea pig aerosol infection model of pulmonary tuberculosis. Protection was measured as survival at 30 weeks post-challenge and reduced bacterial load and histopathology in lungs and spleen. Results showed that a single oral dose of BCG Moreau (RdJ) or recombinant BCG Moreau (RdJ)-Ag85B-ESAT6, formulated with or without lipid, gave protection equivalent to subcutaneously delivered BCG Danish in the 30 weeks post-challenge survival study. The orally delivered vaccines gave reduced pathology scores in the lungs (three of the four formulations) and spleens (all four formulations) compared to subcutaneously delivered BCG Danish. The oral wild type BCG Moreau (RdJ) in lipid and the unformulated oral wild type BCG Moreau (RdJ) vaccine also gave statistically lower bacterial loads in the lungs and spleens, respectively, compared to subcutaneously delivered BCG Danish. This study provides further evidence to show that lipid formulation does not impair vaccine efficacy and may enhance the delivery and stability of oral vaccines intended for use in countries with poor health infrastructure. Oral delivery also avoids needles (and associated cross-infection risks) and immunisation without the need for specially trained

Economic analysis of pandemic influenza vaccination strategies in Singapore.

PubMed

Lee, Vernon J; Tok, Mei Yin; Chow, Vincent T; Phua, Kai Hong; Ooi, Eng Eong; Tambyah, Paul A; Chen, Mark I

2009-09-22

All influenza pandemic plans advocate pandemic vaccination. However, few studies have evaluated the cost-effectiveness of different vaccination strategies. This paper compares the economic outcomes of vaccination compared with treatment with antiviral agents alone, in Singapore. We analyzed the economic outcomes of pandemic vaccination (immediate vaccination and vaccine stockpiling) compared with treatment-only in Singapore using a decision-based model to perform cost-benefit and cost-effectiveness analyses. We also explored the annual insurance premium (willingness to pay) depending on the perceived risk of the next pandemic occurring. The treatment-only strategy resulted in 690 deaths, 13,950 hospitalization days, and economic cost of USD$497 million. For immediate vaccination, at vaccine effectiveness of >55%, vaccination was cost-beneficial over treatment-only. Vaccine stockpiling is not cost-effective in most scenarios even with 100% vaccine effectiveness. The annual insurance premium was highest with immediate vaccination, and was lower with increased duration to the next pandemic. The premium was also higher with higher vaccine effectiveness, attack rates, and case-fatality rates. Stockpiling with case-fatality rates of 0.4-0.6% would be cost-beneficial if vaccine effectiveness was >80%; while at case-fatality of >5% stockpiling would be cost-beneficial even if vaccine effectiveness was 20%. High-risk sub-groups warrant higher premiums than low-risk sub-groups. The actual pandemic vaccine effectiveness and lead time is unknown. Vaccine strategy should be based on perception of severity. Immediate vaccination is most cost-effective, but requires vaccines to be available when required. Vaccine stockpiling as insurance against worst-case scenarios is also cost-effective. Research and development is therefore critical to develop and stockpile cheap, readily available effective vaccines.

A systematic review and meta-analysis for the adverse effects, immunogenicity and efficacy of Lyme disease vaccines: Guiding novel vaccine development.

PubMed

Badawi, Alaa; Shering, Maria; Rahman, Shusmita; Lindsay, L Robbin

2017-04-20

Lyme borreliosis (LB) is the most prevalent arthropod-borne infectious disease in North America. Currently, no vaccine is available to prevent LB in humans, although monovalent and multivalent vaccines have been developed in the past. The aim of the current study is to conduct a systematic review and meta-analysis to evaluate and compare the findings from these two classes of vaccines for their reactogenicity, immunogenicity and efficacy, in the hope this may assist in the development of future vaccines. A search strategy was developed for online databases (PubMed, Ovid MEDLINE, and Embase). Search terms used were "vaccine/vaccination", "Lyme disease/Borreliosis", "clinical trial(s)" and "efficacy". Only seven clinical trials were included to compare the results of the monovalent vaccines to those of the multivalent one. Meta-analyses were conducted to evaluate the reactogenicity and immunogenicity of the two vaccine classes. Odds ratio (OR) for LB (and 95% confidence intervals; 95% CI) were calculated for the efficacy of the monovalent vaccine from three different clinical trials at different dose schedules. Incidence of redness (local adverse effect) and fever (systemic side effect) were, respectively, 6.8- and 2.9-fold significantly lower (p < 0.05) in individuals who received multivalent vaccines compared to those receiving the monovalent one. Incidences of all other local and systemic adverse effects were non-significantly lower in the multivalent vaccine compared to the monovalent vaccines. Seroprotection was comparable among individuals who received the two vaccine classes at the 30 μg dose level. Efficacy in the prevention of LB was only evaluated for the monovalent vaccines. OR of LB ranged from 0.49 (95% CI: 0.14-0.70; p < 0.005, vs. placebo) to 0.31 (95% CI: 0.26-0.63; p < 0.005) for the initial and final doses respectively, with an overall OR of 0.4 (95% CI: 0.26-0.63, p < 0.001). The current study further validates that the monovalent and

Vaccines for preventing typhoid fever.

PubMed

Anwar, Elspeth; Goldberg, Elad; Fraser, Abigail; Acosta, Camilo J; Paul, Mical; Leibovici, Leonard

2014-01-02

Typhoid fever and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and southeast Asia. Two typhoid vaccines are commercially available, Ty21a (oral) and Vi polysaccharide (parenteral), but neither is used routinely. Other vaccines, such as a new, modified, conjugated Vi vaccine called Vi-rEPA, are in development. To evaluate the efficacy and adverse effects of vaccines used to prevent typhoid fever. In June 2013, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, and mRCT. We also searched relevant conference proceedings up to 2013 and scanned the reference lists of all included trials. Randomized and quasi-randomized controlled trials (RCTs) comparing typhoid fever vaccines with other typhoid fever vaccines or with an inactive agent (placebo or vaccine for a different disease). Two review authors independently applied inclusion criteria and extracted data. We computed vaccine efficacy per year of follow-up and cumulative three-year efficacy, stratifying for vaccine type and dose. The outcome addressed was typhoid fever, defined as isolation of Salmonella typhi in blood. We calculated risk ratios (RRs) and efficacy (1-RR as a percentage) with 95% confidence intervals (CIs). In total, 18 RCTs were included in this review; 12 evaluated efficacy (Ty21a: five trials; Vi polysaccharide: six trials; Vi-rEPA: one trial), and 11 reported on adverse events. Ty21a vaccine (oral vaccine, three doses) A three-dose schedule of Ty21a vaccine prevents around one-third to one-half of typhoid cases in the first two years after vaccination (Year 1: 35%, 95% CI 8% to 54%; Year 2: 58%, 95% CI 40% to 71%; one trial, 20,543 participants; moderate quality evidence; data taken from a single trial conducted in Indonesia in the 1980s). No benefit was detected in the third year after vaccination. Four additional cluster-RCTs have been conducted, but the

Anaphylaxis following quadrivalent human papillomavirus vaccination

PubMed Central

Brotherton, Julia M.L.; Gold, Mike S.; Kemp, Andrew S.; McIntyre, Peter B.; Burgess, Margaret A.; Campbell-Lloyd, Sue

2008-01-01

Background In 2007, Australia implemented the National human papillomavirus (HPV) Vaccination Program, which provides quadrivalent HPV vaccine free to all women aged 12–26 years. Following notification of 7 presumptive cases of anaphylaxis in the state of New South Wales, Australia, we verified cases and compared the incidence of anaphylaxis following HPV vaccination to other vaccines in comparable settings. Methods We contacted all patients with suspected anaphylaxis and obtained detailed histories from telephone interviews and a review of medical records. A multidisciplinary team determined whether each suspected case met the standardized Brighton definition. Some participants also received skin-prick allergy testing for common antigens and components of the HPV vaccine. Results Of 12 suspected cases, 8 were classified as anaphylaxis. Of these, 4 participants had negative skin-prick test results for intradermal Gardasil. From the 269 680 HPV vaccine doses administered in schools, 7 cases of anaphylaxis were identified, which represents an incidence rate of 2.6 per 100 000 doses (95% CI 1.0–5.3 per 100 000). In comparison, the rate of identified anaphylaxis was 0.1 per 100 000 doses (95% CI 0.003–0.7) for conjugated meningococcal C vaccination in a 2003 school-based program. Interpretation Based on the number of confirmed cases, the estimated rate of anaphylaxis following quadrivalent HPV vaccine was significantly higher than identified in comparable school-based delivery of other vaccines. However, overall rates were very low and managed appropriately with no serious sequelae. PMID:18762618

Significance of electronic health records: A comparative study of vaccination rates in patients with sickle cell disease.

PubMed

Korur, Asli; Asma, Süheyl; Gereklioglu, Cigdem; Solmaz, Soner; Boga, Can; Ozsahin, Akatlı Kürsat; Kut, Altug

2017-01-01

In this study, we investigated the influence of electronic health records (EHR) and electronic vaccination schedule applications on the vaccination status of patients who were admitted to our Center for the treatment of sickle cell disease (SCD). The vaccination status against influenza and pneumococcus infection was determined in 93 patients who were admitted to the hematology outpatient clinic, Baskent University Adana Hospital from April 2004 to March 2009. The vaccination status was then re-evaluated following establishment of EHR and electronic vaccination schedules in 2012. Of the 93 patients with SCD 21.5% (n = 20) were vaccinated against pneumococcus and 21.5% (n = 20) were regularly vaccinated against influenza. When the vaccination rates of 59 of 93 patients who presented for their regular control examinations were analyzed following establishment of EHR and vaccination schedules in 2012, these rates were 49.2% (n = 29) and 50.8% (n = 30) for influenza and pneumococcus, respectively, after EHR; there were 23.7% (n = 14) and 20.3% (n = 12), respectively, before EHR. A statistically significant difference was found between the vaccination rates before and after EHR (p < 0.05). Although viral and bacterial infections are life-threatening health problems in patients with SCD, the vaccination rates were low in high-risk patients. However, these rates increased after application of electronic vaccination schedules.

Significance of electronic health records: A comparative study of vaccination rates in patients with sickle cell disease

PubMed Central

Korur, Asli; Asma, Süheyl; Gereklioglu, Cigdem; Solmaz, Soner; Boga, Can; Ozsahin, Akatlı Kürsat; Kut, Altug

2017-01-01

Objective: In this study, we investigated the influence of electronic health records (EHR) and electronic vaccination schedule applications on the vaccination status of patients who were admitted to our Center for the treatment of sickle cell disease (SCD). Methods: The vaccination status against influenza and pneumococcus infection was determined in 93 patients who were admitted to the hematology outpatient clinic, Baskent University Adana Hospital from April 2004 to March 2009. The vaccination status was then re-evaluated following establishment of EHR and electronic vaccination schedules in 2012. Results: Of the 93 patients with SCD 21.5% (n = 20) were vaccinated against pneumococcus and 21.5% (n = 20) were regularly vaccinated against influenza. When the vaccination rates of 59 of 93 patients who presented for their regular control examinations were analyzed following establishment of EHR and vaccination schedules in 2012, these rates were 49.2% (n = 29) and 50.8% (n = 30) for influenza and pneumococcus, respectively, after EHR; there were 23.7% (n = 14) and 20.3% (n = 12), respectively, before EHR. A statistically significant difference was found between the vaccination rates before and after EHR (p < 0.05). Conclusion: Although viral and bacterial infections are life-threatening health problems in patients with SCD, the vaccination rates were low in high-risk patients. However, these rates increased after application of electronic vaccination schedules. PMID:28811769

Re-designing the Mozambique vaccine supply chain to improve access to vaccines.

PubMed

Lee, Bruce Y; Haidari, Leila A; Prosser, Wendy; Connor, Diana L; Bechtel, Ruth; Dipuve, Amelia; Kassim, Hidayat; Khanlawia, Balbina; Brown, Shawn T

2016-09-22

Populations and routine childhood vaccine regimens have changed substantially since supply chains were designed in the 1980s, and introducing new vaccines during the "Decade of Vaccine" may exacerbate existing bottlenecks, further inhibiting the flow of all vaccines. Working with the Mozambique Ministry of Health, our team implemented a new process that integrated HERMES computational simulation modeling and on-the-ground implementers to evaluate and improve the Mozambique vaccine supply chain using a system-re-design that integrated new supply chain structures, information technology, equipment, personnel, and policies. The alternative system design raised vaccine availability (from 66% to 93% in Gaza; from 76% to 84% in Cabo Delgado) and reduced the logistics cost per dose administered (from $0.53 to $0.32 in Gaza; from $0.38 to $0.24 in Cabo Delgado) as compared to the multi-tiered system under the current EPI. The alternative system also produced higher availability at lower costs after new vaccine introductions. Since reviewing scenarios modeling deliveries every two months in the north of Gaza, the provincial directorate has decided to pilot this approach diverging from decades of policies dictating monthly deliveries. Re-design improved not only supply chain efficacy but also efficiency, important since resources to deliver vaccines are limited. The Mozambique experience and process can serve as a model for other countries during the Decade of Vaccines. For the Decade of Vaccines, getting vaccines at affordable prices to the market is not enough. Vaccines must reach the population to be successful. Copyright © 2016. Published by Elsevier Ltd.

Long-term Persistence of Zoster Vaccine Efficacy

PubMed Central

Morrison, Vicki A.; Johnson, Gary R.; Schmader, Kenneth E.; Levin, Myron J.; Zhang, Jane H.; Looney, David J.; Betts, Robert; Gelb, Larry; Guatelli, John C.; Harbecke, Ruth; Pachucki, Connie; Keay, Susan; Menzies, Barbara; Griffin, Marie R.; Kauffman, Carol A.; Marques, Adriana; Toney, John; Boardman, Kathy; Su, Shu-Chih; Li, Xiaoming; Chan, Ivan S. F.; Parrino, Janie; Annunziato, Paula; Oxman, Michael N.; Davis, LE.; Kauffman, CA; Keay, SK; Straus, SE; Marques, AR; Soto, NE; Brunell, P; Gnann, JW; Serrao, R; Cotton, DJ; Goodman, RP; Arbeit, RD; Pachucki, CT; Levin, MJ; Schmader, KE; Keitel, WA; Greenberg, RN; Morrison, VA; Wright, PF; Griffin, MR; Simberkoff, MS; Yeh, SS; Lobo, Z; Holodniy, M; Loutit, J; Betts, RF; Gelb, LD; Crawford, GE; Guatelli, J; Brooks, PA; Looney, DJ; Neuzil, KM; Toney, JF; Kauffman, CA; Keay, SK; Marques, AR; Pachucki, CT; Levin, MJ; Schmader, KE; Morrison, VA; Wright, PF; Griffin, MR; Betts, RF; Gelb, LD; Guatelli, JC; Looney, DJ; Neuzil, KM; Menzies, B; Toney, JF

2015-01-01

Background. The Shingles Prevention Study (SPS) demonstrated zoster vaccine efficacy through 4 years postvaccination. A Short-Term Persistence Substudy (STPS) demonstrated persistence of vaccine efficacy for at least 5 years. A Long-Term Persistence Substudy (LTPS) was undertaken to further assess vaccine efficacy in SPS vaccine recipients followed for up to 11 years postvaccination. Study outcomes were assessed for the entire LTPS period and for each year from 7 to 11 years postvaccination. Methods. Surveillance, case determination, and follow-up were comparable to those in SPS and STPS. Because SPS placebo recipients were offered zoster vaccine before the LTPS began, there were no unvaccinated controls. Instead, SPS and STPS placebo results were used to model reference placebo groups. Results. The LTPS enrolled 6867 SPS vaccine recipients. Compared to SPS, estimated vaccine efficacy in LTPS decreased from 61.1% to 37.3% for the herpes zoster (HZ) burden of illness (BOI), from 66.5% to 35.4% for incidence of postherpetic neuralgia, and from 51.3% to 21.1% for incidence of HZ, and declined for all 3 outcome measures from 7 through 11 years postvaccination. Vaccine efficacy for the HZ BOI was significantly greater than zero through year 10 postvaccination, whereas vaccine efficacy for incidence of HZ was significantly greater than zero only through year 8. Conclusions. Estimates of vaccine efficacy decreased over time in the LTPS population compared with modeled control estimates. Statistically significant vaccine efficacy for HZ BOI persisted into year 10 postvaccination, whereas statistically significant vaccine efficacy for incidence of HZ persisted only through year 8. PMID:25416754

Immunogenicity and safety of LBVH0101, a new Haemophilus influenzae type b tetanus toxoid conjugate vaccine, compared with Hiberix™ in Korean infants and children: a randomized trial.

PubMed

Kim, Kyung-Hyo; Kim, Yun-Kyung; Kim, Nam Hee; Chang, Sung Hee; Lee, Jina; Park, Eun Ae; Park, Su Eun; Eun, Byung Wook; Lee, Hyunju; Lee, Hoan Jong

2012-02-27

The World Health Organization (WHO) recommends that all countries adopt Haemophilus influenzae type b (Hib) vaccine into routine child immunization programs to protect children from the significant burden of life-threatening pneumonia and meningitis. In this blind, comparative, randomized, phase-III Korean multicenter study, we assessed immunogenicity and safety following primary vaccination of a new H. influenzae type b tetanus toxoid conjugate vaccine, LBVH0101 (LG Life Sciences, Ltd., Seoul, Korea) compared with Hiberix™ (GSK, Rixensart, Belgium) in Korean children at 2, 4 and 6 months of age followed by a booster vaccination at 12-15 months. Serum anti-PRP IgG concentration and bactericidal activity were determined. Local/systemic symptoms were assessed after vaccination. Serious adverse events were recorded throughout the study. A total of 185 infants were included in immunogenicity evaluations. After the second and third doses of LBVH0101, 90.32% and 100% of infants achieved an antibody level ≥1 μg/mL, respectively, compared with 78.26% and 96.74% of those who received Hiberix™. After the second vaccination, the geometric mean concentration (GMC) of LBVH0101 recipients was 7.34 μg/mL and was higher than that of Hiberix™ recipients (3.55 μg/mL). After the third vaccination, the GMCs were 14.59 μg/mL and 12.15 μg/mL in the LBVH0101 and Hiberix™ recipients, respectively. The booster dose produced higher antibody concentrations: 30.25 μg/mL and 71.64 μg/mL for LBVH0101 and Hiberix™ recipients, respectively. Bactericidal capacity and antibody potency of anti-PRP IgG induced by LBVH0101 was 35.05 and 116.27 after the second and third vaccinations, respectively, compared with 53.76 and 79.64 for Hiberix™. Anti-PRP IgG seroprotection rate and GMC were similar post-primary immunization between the groups; both showed functional maturation and similar booster responses. LBVH0101 had comparable safety results as the control vaccine, Hiberix™, as

Ebola Vaccination Using a DNA Vaccine Coated on PLGA-PLL/γPGA Nanoparticles Administered Using a Microneedle Patch.

PubMed

Yang, Hung-Wei; Ye, Ling; Guo, Xin Dong; Yang, Chinglai; Compans, Richard W; Prausnitz, Mark R

2017-01-01

Ebola DNA vaccine is incorporated into PLGA-PLL/γPGA nanoparticles and administered to skin using a microneedle (MN) patch. The nanoparticle delivery system increases vaccine thermostability and immunogenicity compared to free vaccine. Vaccination by MN patch produces stronger immune responses than intramuscular administration. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An estimate of the public health impact and cost-effectiveness of universal vaccination with a 9-valent HPV vaccine in Germany.

PubMed

Largeron, Nathalie; Petry, Karl Ulrich; Jacob, Jorge; Bianic, Florence; Anger, Delphine; Uhart, Mathieu

2017-02-01

Since 2007, the German Standing Vaccination Committee recommends HPV vaccination for girls aged 12-17 with a 2- (Cervarix®) or 4-valent (Gardasil®) vaccine. A 9-valent vaccine (Gardasil 9®) recently received a European market authorization in 2015. A dynamic transmission model was calibrated to the German setting and used to estimate costs and QALYs associated with vaccination strategies. Compared to the current vaccination program, the 9-valent vaccine extended to boys shows further reductions of 24% in the incidence of cervical cancer, 30% and 14% in anal cancer for males and females, as well as over a million cases of genital warts avoided after 100 years. The new strategy is associated with an ICER of 22,987€ per QALY gained, decreasing to 329€ when considering the vaccine switch for girls-only. Universal vaccination with the 9-valent vaccine can yield significant health benefits when compared to the current program.

Ten years of PCV2 vaccines and vaccination: Is eradication a possibility?

PubMed

Afghah, Zahra; Webb, Brett; Meng, Xiang-Jin; Ramamoorthy, Sheela

2017-07-01

More than two decades after its emergence, porcine circovirus type 2 (PCV2) remains an economically important swine pathogen. Commercial vaccines which were first introduced to the U.S in 2006, have been highly effective in reducing clinical signs and improving production. Recent studies have indicated a declining level of PCV2 prevalence and viremia in the field. However, reports on the emergence of new viral variants have also continued to increase. This article reviews topics of current interest in the field of PCV2 vaccines; including the comparative efficacy of the available commercial products, efficacy of current vaccines against new and emerging strains, findings on the differences between immunity in natural infection versus vaccination, limitations of current experimental models for PCV2 vaccine studies, and new developments in novel experimental vaccines. The discussion is framed in the context of attempts for the possible eradication of PCV2 in the future. Copyright © 2016 Elsevier B.V. All rights reserved.

Virus-Vectored Influenza Virus Vaccines

PubMed Central

Tripp, Ralph A.; Tompkins, S. Mark

2014-01-01

Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines. PMID:25105278

Influence of oral polio vaccines on performance of the monovalent and pentavalent rotavirus vaccines.

PubMed

Patel, Manish; Steele, A Duncan; Parashar, Umesh D

2012-04-27

In recent years, two live, oral rotavirus vaccines have been successfully tested in developing and industrialized countries, and both vaccines are now recommended by the World Health Organization for all children worldwide. Both immunogenicity and efficacy of these rotavirus vaccines has been lower in developing compared to industrialized settings. We reviewed the data on the effect of trivalent OPV on the immunogenicity and efficacy of two rotavirus vaccines currently recommended by the WHO. While rotavirus vaccines have not affected immune responses to OPV, in general, the immune responses (i.e., antibody levels) to rotavirus vaccination were lower when rotavirus vaccines were co-administered with OPV. Limited data suggests that the interference is greater after the first dose of OPV, presumably because the first dose is associated with greatest intestinal replication of vaccine polio virus strains, and this interference is largely overcome with subsequent rotavirus vaccine doses. Despite the lower immunogenicity, one large efficacy study in middle income Latin American countries showed no decrease in protective efficacy of rotavirus vaccine in infants receiving concurrent OPV. While these data are encouraging and support simultaneous administration of rotavirus vaccines and OPV, additional evidence should be gathered as rotavirus vaccines are used more widely in developing country settings, where OPV is routinely used, rather than inactivated polio vaccine. Published by Elsevier Ltd.

Modular vaccine packaging increases packing efficiency

PubMed Central

Norman, Bryan A.; Rajgopal, Jayant; Lim, Jung; Gorham, Katrin; Haidari, Leila; Brown, Shawn T.; Lee, Bruce Y.

2015-01-01

Background Within a typical vaccine supply chain, vaccines are packaged into individual cylindrical vials (each containing one or more doses) that are bundled together in rectangular “inner packs” for transport via even larger groupings such as cold boxes and vaccine carriers. The variability of vaccine inner pack and vial size may hinder efficient vaccine distribution because it constrains packing of cold boxes and vaccine carriers to quantities that are often inappropriate or suboptimal in the context of country-specific vaccination guidelines. Methods We developed in Microsoft Excel (Microsoft Corp., Redmond, WA) a spreadsheet model that evaluated the impact of different packing schemes for the Benin routine regimen plus the introduction of the Rotarix vaccine. Specifically, we used the model to compare the current packing scheme to that of a proposed modular packing scheme. Results Conventional packing of a Dometic RCW25 that aims to maximize fully-immunized children (FICs) results in 123 FICs and a packing efficiency of 81.93% compared to a maximum of 155 FICs and 94.1% efficiency for an alternative modular packaging system. Conclusions Our analysis suggests that modular packaging systems could offer significant advantages over conventional vaccine packaging systems with respect to space efficiency and potential FICs, when they are stored in standard vaccine carrying devices. This allows for more vaccines to be stored within the same volume while also simplifying the procedures used by field workers to pack storage devices. Ultimately, modular packaging systems could be a simple way to help increase vaccine coverage worldwide. PMID:25957666

Hepatitis B Vaccination Status among Japanese Travelers.

PubMed

Yaita, Kenichiro; Yahara, Koji; Sakai, Yoshiro; Iwahashi, Jun; Masunaga, Kenji; Hamada, Nobuyuki; Watanabe, Hiroshi

2017-05-08

This study clarified the characteristics of travelers who received hepatitis B vaccinations. Subjects were 233 Japanese travelers who visited our clinic prior to travel. We summarized the characteristics of the clients and performed two comparative studies: first, we compared a hepatitis B-vaccinated group with an unvaccinated group; second, we compared a group that had completed the hepatitis B vaccine series with a group that did not complete the series. The hepatitis B vaccine was administered to 152 clients. Factors positively associated with the hepatitis B vaccination (after adjusting for age and sex) included the following: travel for business or travel as an accompanying family member; travel to Asia; travel for a duration of a month or more; and, inclusion of the vaccine in a company or organization's payment plan. Meanwhile, factors negatively associated with the vaccination were travel for leisure or education, and travel to North America or Africa. Among 89 record-confirmed cases, only 53 completed 3 doses. The completion rate was negatively associated with the scheduled duration of travel if it was from a month to less than a year (after adjusting for age and sex). The present study provides a basis for promoting vaccination compliance more vigorously among Japanese adults.

Proteomic profile of culture filtrate from the Brazilian vaccine strain Mycobacterium bovis BCG Moreau compared to M. bovis BCG Pasteur

PubMed Central

2011-01-01

Background Bacille Calmette-Guerin (BCG) is currently the only available vaccine against tuberculosis (TB) and comprises a heterogeneous family of sub-strains with genotypic and phenotypic differences. The World Health Organization (WHO) affirms that the characterization of BCG sub-strains, both on genomic and proteomic levels, is crucial for a better comprehension of the vaccine. In addition, these studies can contribute in the development of a more efficient vaccine against TB. Here, we combine two-dimensional electrophoresis (2DE) and mass spectrometry to analyse the proteomic profile of culture filtrate proteins (CFPs) from M. bovis BCG Moreau, the Brazilian vaccine strain, comparing it to that of BCG Pasteur. CFPs are considered of great importance given their dominant immunogenicity and role in pathogenesis, being available for interaction with host cells since early infection. Results The 2DE proteomic map of M. bovis BCG Moreau CFPs in the pH range 3 - 8 allowed the identification of 158 spots corresponding to 101 different proteins, identified by MS/MS. Comparison to BCG Pasteur highlights the great similarity between these BCG strains. However, quantitative analysis shows a higher expression of immunogenic proteins such as Rv1860 (BCG1896, Apa), Rv1926c (BCG1965c, Mpb63) and Rv1886c (BCG1923c, Ag85B) in BCG Moreau when compared to BCG Pasteur, while some heat shock proteins, such as Rv0440 (BCG0479, GroEL2) and Rv0350 (BCG0389, DnaK), show the opposite pattern. Conclusions Here we report the detailed 2DE profile of CFPs from M. bovis BCG Moreau and its comparison to BCG Pasteur, identifying differences that may provide relevant information on vaccine efficacy. These findings contribute to the detailed characterization of the Brazilian vaccine strain against TB, revealing aspects that may lead to a better understanding of the factors leading to BCG's variable protective efficacy against TB. PMID:21507239

Cost-Effectiveness Analysis of Hepatitis B Vaccination Strategies to Prevent Perinatal Transmission in North Korea: Selective Vaccination vs. Universal Vaccination.

PubMed

Lee, Donghoon; Park, Sang Min

2016-01-01

To tackle the high prevalence of Hepatitis B virus (HBV) infection in North Korea, it is essential that birth doses of HBV vaccines should be administered within 24 hours of birth. As the country fails to provide a Timely Birth Dose (TBD) of HBV vaccine, the efforts of reducing the high prevalence of HBV have been significantly hampered. To examine the cost-effectiveness of vaccination strategies to prevent perinatal transmission of HBV in North Korea, we established a decision tree with a Markov model consisting of selective, universal, and the country's current vaccination program against HBV. The cost-effectiveness analysis was performed from societal and payer's perspectives and evaluated by Disability Adjusted Life Year (DALY). The results suggest that introducing the universal vaccination would prevent 1,866 cases of perinatal infections per 100,000 of the birth cohort of 2013. Furthermore, 900 cases of perinatal infections per 100,000 could be additionally averted if switching to the selective vaccination. The current vaccination is a dominated strategy both from the societal and payer's perspective. The Incremental Cost-Effectiveness Ratio (ICER) between universal and selective vaccination is $267 from the societal perspective and is reported as $273 from the payer's perspective. Based on the assumption that the 2012 Gross Domestic Product (GDP) per capita in North Korea, $582.6 was set for cost-effectiveness criteria, the result of this study indicates that selective vaccination may be a highly cost-effective strategy compared to universal vaccination.

Vaccination Programs for Endemic Infections: Modelling Real versus Apparent Impacts of Vaccine and Infection Characteristics

NASA Astrophysics Data System (ADS)

Ragonnet, Romain; Trauer, James M.; Denholm, Justin T.; Geard, Nicholas L.; Hellard, Margaret; McBryde, Emma S.

2015-10-01

Vaccine effect, as measured in clinical trials, may not accurately reflect population-level impact. Furthermore, little is known about how sensitive apparent or real vaccine impacts are to factors such as the risk of re-infection or the mechanism of protection. We present a dynamic compartmental model to simulate vaccination for endemic infections. Several measures of effectiveness are calculated to compare the real and apparent impact of vaccination, and assess the effect of a range of infection and vaccine characteristics on these measures. Although broadly correlated, measures of real and apparent vaccine effectiveness can differ widely. Vaccine impact is markedly underestimated when primary infection provides partial natural immunity, when coverage is high and when post-vaccination infectiousness is reduced. Despite equivalent efficacy, ‘all or nothing’ vaccines are more effective than ‘leaky’ vaccines, particularly in settings with high risk of re-infection and transmissibility. Latent periods result in greater real impacts when risk of re-infection is high, but this effect diminishes if partial natural immunity is assumed. Assessments of population-level vaccine effects against endemic infections from clinical trials may be significantly biased, and vaccine and infection characteristics should be considered when modelling outcomes of vaccination programs, as their impact may be dramatic.

Vaccination Programs for Endemic Infections: Modelling Real versus Apparent Impacts of Vaccine and Infection Characteristics

PubMed Central

Ragonnet, Romain; Trauer, James M.; Denholm, Justin T.; Geard, Nicholas L.; Hellard, Margaret; McBryde, Emma S.

2015-01-01

Vaccine effect, as measured in clinical trials, may not accurately reflect population-level impact. Furthermore, little is known about how sensitive apparent or real vaccine impacts are to factors such as the risk of re-infection or the mechanism of protection. We present a dynamic compartmental model to simulate vaccination for endemic infections. Several measures of effectiveness are calculated to compare the real and apparent impact of vaccination, and assess the effect of a range of infection and vaccine characteristics on these measures. Although broadly correlated, measures of real and apparent vaccine effectiveness can differ widely. Vaccine impact is markedly underestimated when primary infection provides partial natural immunity, when coverage is high and when post-vaccination infectiousness is reduced. Despite equivalent efficacy, ‘all or nothing’ vaccines are more effective than ‘leaky’ vaccines, particularly in settings with high risk of re-infection and transmissibility. Latent periods result in greater real impacts when risk of re-infection is high, but this effect diminishes if partial natural immunity is assumed. Assessments of population-level vaccine effects against endemic infections from clinical trials may be significantly biased, and vaccine and infection characteristics should be considered when modelling outcomes of vaccination programs, as their impact may be dramatic. PMID:26482413

Near Real-Time Surveillance for Influenza Vaccine Safety: Proof-of-Concept in the Vaccine Safety Datalink Project

PubMed Central

Greene, Sharon K.; Kulldorff, Martin; Lewis, Edwin M.; Li, Rong; Yin, Ruihua; Weintraub, Eric S.; Fireman, Bruce H.; Lieu, Tracy A.; Nordin, James D.; Glanz, Jason M.; Baxter, Roger; Jacobsen, Steven J.; Broder, Karen R.; Lee, Grace M.

2010-01-01

The emergence of pandemic H1N1 influenza in 2009 has prompted public health responses, including production and licensure of new influenza A (H1N1) 2009 monovalent vaccines. Safety monitoring is a critical component of vaccination programs. As proof-of-concept, the authors mimicked near real-time prospective surveillance for prespecified neurologic and allergic adverse events among enrollees in 8 medical care organizations (the Vaccine Safety Datalink Project) who received seasonal trivalent inactivated influenza vaccine during the 2005/06–2007/08 influenza seasons. In self-controlled case series analysis, the risk of adverse events in a prespecified exposure period following vaccination was compared with the risk in 1 control period for the same individual either before or after vaccination. In difference-in-difference analysis, the relative risk in exposed versus control periods each season was compared with the relative risk in previous seasons since 2000/01. The authors used Poisson-based analysis to compare the risk of Guillian-Barré syndrome following vaccination in each season with that in previous seasons. Maximized sequential probability ratio tests were used to adjust for repeated analyses on weekly data. With administration of 1,195,552 doses to children under age 18 years and 4,773,956 doses to adults, no elevated risk of adverse events was identified. Near real-time surveillance for selected adverse events can be implemented prospectively to rapidly assess seasonal and pandemic influenza vaccine safety. PMID:19965887

Cost-effectiveness analysis of AS04-adjuvanted human papillomavirus 16/18 vaccine compared with human papillomavirus 6/11/16/18 vaccine in the Philippines, with the new 2-dose schedule.

PubMed

Germar, Maria Julieta; Purugganan, Carrie; Bernardino, Ma Socorro; Cuenca, Benjamin; Chen, Y-Chen; Li, Xiao; Van Kriekinge, Georges; Lee, I-Heng

2017-05-04

Cervical cancer (CC) is the second leading cause of cancer death among Filipino women. Human papillomavirus (HPV) vaccination protects against CC. Two vaccines (AS04-HPV-16/18 and 4vHPV) are approved in the Philippines; they were originally developed for a 3-dose (3D) administration and have recently been approved in a 2-dose schedule (2D). This study aims to evaluate the cost-effectiveness of HPV vaccination of 13-year-old Filipino girls, in addition to current screening, in the new 2D schedule. An existing static lifetime, one-year cycle Markov cohort model was adapted to the Philippine settings to simulate the natural history of low-risk and oncogenic HPV infection, the effects of screening and vaccination of a 13-year-old girls cohort vaccinated with either the 2D-AS04-HPV-16/18 or 2D-4vHPV assuming a 100% vaccination coverage. Incremental cost, quality-adjusted life year (QALY) and cost-effectiveness were derived from these estimates. Input data were obtained from published sources and Delphi panel, using country-specific data where possible. Sensitivity analyses were performed to assess the robustness of the model. The model estimated that 2D-AS04-HPV-16/18 prevented 986 additional CC cases and 399 CC deaths (undiscounted), as well as 555 increased QALY (discounted), and save 228.1 million Philippine pesos (PHP) compared with the 2D-4vHPV. In conclusion, AS04-HPV-16/18 is shown to be dominant over 4vHPV in the Philippines, with greater estimated health benefits and lower costs.

Cost-effectiveness analysis of AS04-adjuvanted human papillomavirus 16/18 vaccine compared with human papillomavirus 6/11/16/18 vaccine in the Philippines, with the new 2-dose schedule

PubMed Central

Germar, Maria Julieta; Purugganan, Carrie; Bernardino, Ma. Socorro; Cuenca, Benjamin; Chen, Y-Chen; Li, Xiao; Van Kriekinge, Georges; Lee, I-Heng

2017-01-01

ABSTRACT Cervical cancer (CC) is the second leading cause of cancer death among Filipino women. Human papillomavirus (HPV) vaccination protects against CC. Two vaccines (AS04-HPV-16/18 and 4vHPV) are approved in the Philippines; they were originally developed for a 3-dose (3D) administration and have recently been approved in a 2-dose schedule (2D). This study aims to evaluate the cost-effectiveness of HPV vaccination of 13-year-old Filipino girls, in addition to current screening, in the new 2D schedule. An existing static lifetime, one-year cycle Markov cohort model was adapted to the Philippine settings to simulate the natural history of low-risk and oncogenic HPV infection, the effects of screening and vaccination of a 13-year-old girls cohort vaccinated with either the 2D-AS04-HPV-16/18 or 2D-4vHPV assuming a 100% vaccination coverage. Incremental cost, quality-adjusted life year (QALY) and cost-effectiveness were derived from these estimates. Input data were obtained from published sources and Delphi panel, using country-specific data where possible. Sensitivity analyses were performed to assess the robustness of the model. The model estimated that 2D-AS04-HPV-16/18 prevented 986 additional CC cases and 399 CC deaths (undiscounted), as well as 555 increased QALY (discounted), and save 228.1 million Philippine pesos (PHP) compared with the 2D-4vHPV. In conclusion, AS04-HPV-16/18 is shown to be dominant over 4vHPV in the Philippines, with greater estimated health benefits and lower costs. PMID:28075249

Evaluation of scanning 2D barcoded vaccines to improve data accuracy of vaccines administered.

PubMed

Daily, Ashley; Kennedy, Erin D; Fierro, Leslie A; Reed, Jenica Huddleston; Greene, Michael; Williams, Warren W; Evanson, Heather V; Cox, Regina; Koeppl, Patrick; Gerlach, Ken

2016-11-11

Accurately recording vaccine lot number, expiration date, and product identifiers, in patient records is an important step in improving supply chain management and patient safety in the event of a recall. These data are being encoded on two-dimensional (2D) barcodes on most vaccine vials and syringes. Using electronic vaccine administration records, we evaluated the accuracy of lot number and expiration date entered using 2D barcode scanning compared to traditional manual or drop-down list entry methods. We analyzed 128,573 electronic records of vaccines administered at 32 facilities. We compared the accuracy of records entered using 2D barcode scanning with those entered using traditional methods using chi-square tests and multilevel logistic regression. When 2D barcodes were scanned, lot number data accuracy was 1.8 percentage points higher (94.3-96.1%, P<0.001) and expiration date data accuracy was 11 percentage points higher (84.8-95.8%, P<0.001) compared with traditional methods. In multivariate analysis, lot number was more likely to be accurate (aOR=1.75; 99% CI, 1.57-1.96) as was expiration date (aOR=2.39; 99% CI, 2.12-2.68). When controlling for scanning and other factors, manufacturer, month vaccine was administered, and vaccine type were associated with variation in accuracy for both lot number and expiration date. Two-dimensional barcode scanning shows promise for improving data accuracy of vaccine lot number and expiration date records. Adapting systems to further integrate with 2D barcoding could help increase adoption of 2D barcode scanning technology. Published by Elsevier Ltd.

[The National Vaccine Injury Compensation Program in Japan].

PubMed

Ihara, Toshiaki

2011-09-01

Two vaccination systems have been employed in Japan, the routine vaccination and the voluntary vaccination. The National Vaccine Injury Compensation Program in Japan is no-fault system. Claims after the routine vaccination are demanded to the Ministry of Health, Labour and Welfare through local governments, and compensation is more expenses. Meanwhile, claims after the voluntary vaccination are demanded to the Pharmaceuticals and Medical Device Agency directly, and compensation is less compared with the routine vaccination.

Phase III Clinical Trials Comparing the Immunogenicity and Safety of the Vero Cell-Derived Japanese Encephalitis Vaccine Encevac with Those of Mouse Brain-Derived Vaccine by Using the Beijing-1 Strain

PubMed Central

Miyazaki, Chiaki; Okada, Kenji; Ozaki, Takao; Hirose, Mizuo; Iribe, Kaneshige; Ishikawa, Yuji; Togashi, Takehiro; Ueda, Kohji

2014-01-01

The immunogenicity and safety of an inactivated cell culture Japanese encephalitis vaccine (CC-JEV) were compared with those of an inactivated mouse brain-derived Japanese encephalitis vaccine (MB-JEV) in phase III clinical multicenter trials conducted in children. The vaccines contain the same Japanese encephalitis virus strain, the Beijing-1 strain. Two independent clinical trials (trials 1 and 2) were conducted. Trial 1 was conducted in 468 healthy children. Each subject was injected with 17 μg per dose of either CC-JEV or MB-JEV, and the immunogenicity and safety of the vaccines were investigated. Trial 1 showed that CC-JEV was more immunogenic and reactive than MB-JEV at the same dose. Therefore, to adjust the immunogenicity of CC-JEV to that of MB-JEV, a vaccine that has had a good track record regarding its efficacy for a long time, trial 2 was conducted in 484 healthy children. To improve the stability, CC-JEV was converted from a liquid type to a freeze-dried type of vaccine. Each subject was injected subcutaneously with either 4 μg per dose of CC-JEV, 8 μg per dose of CC-JEV, or 17 μg per dose of MB-JEV twice, at an interval of 2 to 4 weeks, followed by an additional booster immunization 1 to 15 months after the primary immunization. Based on the results of trial 2, 4 μg per dose of the freeze-dried CC-JEV (under the label Encevac) was selected as a substitute for the MB-JEV. Encevac was approved and launched in 2011 and has since been in use as a 2nd-generation Japanese encephalitis vaccine in Japan. (These studies have been registered at the JapicCTI under registration no. JapicCTI-132063 and JapicCTI-080586 for trials 1 and 2, respectively.) PMID:24334689

New vaccines against otitis media: projected benefits and cost-effectiveness.

PubMed

O'Brien, Megan A; Prosser, Lisa A; Paradise, Jack L; Ray, G Thomas; Kulldorff, Martin; Kurs-Lasky, Marcia; Hinrichsen, Virginia L; Mehta, Jyotsna; Colborn, D Kathleen; Lieu, Tracy A

2009-06-01

New vaccines that offer protection against otitis media caused by nontypeable Haemophilus influenzae and by Moraxella catarrhalis are under development. However, the potential health benefits and economic effects of such candidate vaccines have not been systematically assessed. We created a computerized model to compare the projected benefits and costs of (1) the currently available 7-valent pneumococcal conjugate vaccine, (2) a candidate pneumococcal-nontypeable H influenzae vaccine that has been tested in Europe, (3) a hypothetical pneumococcal-nontypeable H influenzae-Moraxella vaccine, and (4) no vaccination. The clinical probabilities of acute otitis media and of otitis media with effusion were generated from multivariate analyses of data from 2 large health maintenance organizations and from the Pittsburgh Child Development/Otitis Media Study cohort. Other probabilities, costs, and quality-of-life values were derived from published and unpublished sources. The base-case analysis assumed vaccine dose costs of $65 for the 7-valent pneumococcal conjugate vaccine, $100 for the pneumococcal-nontypeable H influenzae vaccine, and $125 for the pneumococcal-nontypeable H influenzae-Moraxella vaccine. With no vaccination, we projected that 13.7 million episodes of acute otitis media would occur annually in US children aged 0 to 4 years, at an annual cost of $3.8 billion. The 7-valent pneumococcal conjugate vaccine was projected to prevent 878,000 acute otitis media episodes, or 6.4% of those that would occur with no vaccination; the corresponding value for the pneumococcal-nontypeable H influenzae vaccine was 3.7 million (27%) and for the pneumococcal-nontypeable H influenzae-Moraxella vaccine was 4.2 million (31%). Using the base-case vaccine costs, pneumococcal-nontypeable H influenzae vaccine use would result in net savings compared with nontypeable 7-valent pneumococcal conjugate use. Conversely, pneumococcal-nontypeable H influenzae-Moraxella vaccine use would not

Cellular Immune Responses to Nine Mycobacterium tuberculosis Vaccine Candidates following Intranasal Vaccination

PubMed Central

Sable, Suraj B.; Cheruvu, Mani; Nandakumar, Subhadra; Sharma, Sunita; Bandyopadhyay, Kakali; Kellar, Kathryn L.; Posey, James E.; Plikaytis, Bonnie B.; Amara, Rama Rao; Shinnick, Thomas M.

2011-01-01

Background The identification of Mycobacterium tuberculosis vaccines that elicit a protective immune response in the lungs is important for the development of an effective vaccine against tuberculosis. Methods and Principal Findings In this study, a comparison of intranasal (i.n.) and subcutaneous (s.c.) vaccination with the BCG vaccine demonstrated that a single moderate dose delivered intranasally induced a stronger and sustained M. tuberculosis-specific T-cell response in lung parenchyma and cervical lymph nodes of BALB/c mice than vaccine delivered subcutaneously. Both BCG and a multicomponent subunit vaccine composed of nine M. tuberculosis recombinant proteins induced strong antigen-specific T-cell responses in various local and peripheral immune compartments. Among the nine recombinant proteins evaluated, the alanine proline rich antigen (Apa, Rv1860) was highly antigenic following i.n. BCG and immunogenic after vaccination with a combination of the nine recombinant antigens. The Apa-induced responses included induction of both type 1 and type 2 cytokines in the lungs as evaluated by ELISPOT and a multiplexed microsphere-based cytokine immunoassay. Of importance, i.n. subunit vaccination with Apa imparted significant protection in the lungs and spleen of mice against M. tuberculosis challenge. Despite observed differences in the frequencies and location of specific cytokine secreting T cells both BCG vaccination routes afforded comparable levels of protection in our study. Conclusion and Significance Overall, our findings support consideration and further evaluation of an intranasally targeted Apa-based vaccine to prevent tuberculosis. PMID:21799939

Re-designing the Mozambique vaccine supply chain to improve access to vaccines

PubMed Central

Lee, Bruce Y.; Haidari, Leila A.; Prosser, Wendy; Connor, Diana L.; Bechtel, Ruth; Dipuve, Amelia; Kassim, Hidayat; Khanlawia, Balbina; Brown, Shawn T.

2017-01-01

Introduction Populations and routine childhood vaccine regimens have changed substantially since supply chains were designed in the 1980s, and introducing new vaccines during the “Decade of Vaccine” may exacerbate existing bottlenecks, further inhibiting the flow of all vaccines. Methods Working with the Mozambique Ministry of Health, our team implemented a new process that integrated HERMES computational simulation modeling and on-the-ground implementers to evaluate and improve the Mozambique vaccine supply chain using a system-re-design that integrated new supply chain structures, information technology, equipment, personnel, and policies. Results The alternative system design raised vaccine availability (from 66% to 93% in Gaza; from 76% to 84% in Cabo Delgado) and reduced the logistics cost per dose administered (from $0.53 to $0.32 in Gaza; from $0.38 to $0.24 in Cabo Delgado) as compared to the multi-tiered system under the current EPI. The alternative system also produced higher availability at lower costs after new vaccine introductions. Since reviewing scenarios modeling deliveries every two months in the north of Gaza, the provincial directorate has decided to pilot this approach diverging from decades of policies dictating monthly deliveries. Discussion Re-design improved not only supply chain efficacy but also efficiency, important since resources to deliver vaccines are limited. The Mozambique experience and process can serve as a model for other countries during the Decade of Vaccines. For the Decade of Vaccines, getting vaccines at affordable prices to the market is not enough. Vaccines must reach the population to be successful. PMID:27576077

Phase I trial of RV3-BB rotavirus vaccine: a human neonatal rotavirus vaccine.

PubMed

Danchin, M; Kirkwood, C D; Lee, K J; Bishop, R F; Watts, E; Justice, F A; Clifford, V; Cowley, D; Buttery, J P; Bines, J E

2013-05-28

RV3 is a human neonatal rotavirus strain (G3P[6]) that has been associated with asymptomatic neonatal infection and replicates well in the infant gut. RV3-BB rotavirus vaccine has been developed as a rotavirus vaccine candidate for administration at birth. A single-centre, double-blind, randomised placebo-controlled Phase I study evaluated the safety and tolerability of a single oral dose of the second generation RV3-BB rotavirus vaccine (8.3×10(6)FFU/mL) in 20 adults, 20 children and 20 infants (10 vaccine and 10 placebo per age cohort). Vaccine take was defined as seroconversion (a 3-fold increase in serum anti-rotavirus IgA or serum neutralising antibody (SNA) from baseline at day 28 post-dose) or evidence of RV3-BB viral replication in the faeces by RT-PCR analysis 3-6 days post-vaccination. RV3-BB presence was confirmed by sequence analysis. The RV3-BB vaccine was well tolerated in all participants, with no pattern of adverse events shown to be associated with the study vaccine. In the infant cohort, vaccine take was demonstrated in 8/9 infants following a single dose of vaccine compared with 2/7 placebo recipients. In the infant vaccine group, 5/9 infants exhibited either IgA or SNA seroconversion and 7/9 infants had evidence of RV3-BB replication on days 3-6, compared with 2/7 infants who seroconverted and 0/10 infants with evidence of replication in the placebo group. Two infants in the placebo group had serological evidence of a rotavirus infection within the 28-day study period: one demonstrated an IgA and the other an SNA response, with wild-type virus replication detected in another infant. A single dose of RV3-BB rotavirus vaccine was well tolerated in adults, children and infants. Most infants (8/9) who received RV3-BB demonstrated vaccine take following a single dose. These data support progression of RV3-BB to Phase II immunogenicity and efficacy trials. Copyright © 2013 Elsevier Ltd. All rights reserved.

Parents who refuse or delay HPV vaccine: Differences in vaccination behavior, beliefs, and clinical communication preferences

PubMed Central

Gilkey, Melissa B.; Calo, William A.; Marciniak, Macary W.

2017-01-01

ABSTRACT Background: We sought to estimate the national prevalence of HPV vaccine refusal and delay in a nationally-representative sample of parents of adolescents. We also compared parents who refused versus delayed HPV vaccine in terms of their vaccination beliefs and clinical communication preferences. Methods: In 2014 to 2015, we conducted an online survey of 1,484 US parents who reported on an 11- to 17-year-old child in their household. We used weighted multinomial logistic regression to assess correlates of HPV vaccine refusal and delay. Results: Overall, 28% of parents reported that they had ever “refused or decided not to get” HPV vaccine for their child, and an additional 8% of parents reported that they had “delayed or put off getting” HPV vaccine. Compared to no refusal/delay, refusal was associated with lower confidence in adolescent vaccination (relative risk ratio [RRR] = 0.66, 95% confidence interval [CI], 0.48–0.91), lower perceived HPV vaccine effectiveness (RRR = 0.68, 95% CI, 0.50–0.91), and higher perceived harms (RRR = 3.49, 95% CI, 2.65–4.60). In contrast, delay was associated with needing more information (RRR = 1.76, 95% CI, 1.08–2.85). Most parents rated physicians and information sheets as helpful for making decisions about HPV vaccination, although parents who reported refusal endorsed these resources less often. Conclusions: Our findings suggest that HPV vaccine refusal is common among parents of adolescents and may have increased relative to previous estimates. Because the vaccination beliefs and communication preferences of parents who refuse appear to differ from those who delay, targeted communication strategies may be needed to effectively address HPV vaccine hesitancy. PMID:27763818

Systematic literature review comparing rapid 3-dose administration of the GSK tick-borne encephalitis vaccine with other primary immunization schedules.

PubMed

Galgani, Ilaria; Bunge, Eveline M; Hendriks, Lisa; Schludermann, Christopher; Marano, Cinzia; De Moerlooze, Laurence

2017-09-01

Tick-borne encephalitis (TBE), which is endemic across large regions of Europe and Asia, is most effectively prevented through vaccination. Three-dose primary TBE vaccination schedules are either rapid (0,7,21-days) or conventional (0,28-84-days, 9-12-months). The second dose can also be administered at 14 days for faster priming and sero-protection). Areas covered: We used a three-step selection process to identify 21 publications comparing the immunogenicity and/or safety of different schedules. Expert commentary: Priming with two or three TBE vaccine doses was highly immunogenic. After conventional priming (0-28 days), 95% adults and ≥95% children had neutralization test (NT) titers ≥10 at 14 days post-dose-2 compared with 92% adults and 99% children at 21 days post-dose-3 (rapid schedule). Most subjects retained NT titers ≥10 at day 300. A single booster dose induced a strong immune response in all subjects irrespective of primary vaccination schedule or elapsed time since priming. GMT peaked at 42 days post-dose-1 (i.e., 21 days post-dose 3 [rapid-schedule], or 14-28 days post-dose-2 [conventional-schedule]), and declined thereafter. Adverse events were generally rare and declined with increasing doses. In the absence of data to recommend one particular schedule, the regimen choice will remain at the physician's discretion, based on patient constraints and availability.

Estimating the cost-effectiveness profile of a universal vaccination programme with a nine-valent HPV vaccine in Austria.

PubMed

Boiron, L; Joura, E; Largeron, N; Prager, B; Uhart, M

2016-04-16

HPV is a major cancer-causing factor in both sexes in the cervix, vulva, vagina, anus, penis, oropharynx as well as the causal factor in other diseases such as genital warts and recurrent respiratory papillomatis. In the context of the arrival of a nonavalent HPV vaccine (6/11/16/18/31/33/45/52/58), this analysis aims to estimate the public health impact and the incremental cost-effectiveness of a universal (girls and boys) vaccination program with a nonavalent HPV vaccine as compared to the current universal vaccination program with a quadrivalent HPV vaccine (6/11/16/18), in Austria. A dynamic transmission model including a wide range of health and cost outcomes related to cervical, anal, vulvar, vaginal diseases and genital warts was calibrated to Austrian epidemiological data. The clinical impact due to the 5 new types was included for cervical and anal diseases outcomes only. In the base case, a two-dose schedule, lifelong vaccine type-specific protection and a vaccination coverage rate of 60% and 40% for girls and boys respectively for the 9-year old cohorts were assumed. A cost-effectiveness threshold of €30,000/QALY-gained was considered. Universal vaccination with the nonavalent vaccine was shown to reduce the incidence of HPV16/18/31/33/45/52/58 -related cervical cancer by 92%, the related CIN2/3 cases by 96% and anal cancer by 83% and 76% respectively in females and males after 100 years, relative to 75%, 76%, 80% and 74% with the quadrivalent vaccine, respectively. Furthermore, the nonavalent vaccine was projected to prevent an additional 14,893 cases of CIN2/3 and 2544 cases of cervical cancer, over 100 years. Depending on the vaccine price, the strategy was shown to be from cost-saving to cost-effective. The present evaluation showed that vaccinating 60% of girls and 40% of boys aged 9 in Austria with a 9-valent vaccine will substantially reduce the incidence of cervical cancer, CIN and anal cancer compared to the existing strategy. The vaccination

Serological response following re-vaccination with Salmonella typhi Vi-capsular polysaccharide vaccines in healthy adult travellers.

PubMed

Roggelin, Louise; Vinnemeier, Christof D; Fischer-Herr, Johanna; Johnson-Weaver, Brandi T; Rolling, Thierry; Burchard, Gerd D; Staats, Herman F; Cramer, Jakob P

2015-08-07

An injectable Vi-capsular polysaccharide vaccine against typhoid fever is available but vaccine-induced immunity tends to wane over time. The phenomenon of immunotolerance or hyporesponsiveness has earlier been described for polysaccharide vaccines such as pneumococcal capsular polysaccharide vaccine and some publications also suggest a possible immunotolerance after revaccination with Vi-capsular polysaccharide vaccines. In this study, post-immunisation antibody concentrations in adult travellers first vaccinated with a Salmonella typhi Vi-capsular polysaccharide vaccine (primary vaccination group) were compared with those having received one or more vaccinations previously (multiple vaccinations group). Vaccines administered were Typherix(®) (GlaxoSmithKline), Typhim Vi(®) (Sanofi Pasteur MSD) or Hepatyrix(®) (GlaxoSmithKline). Blood samples were obtained prior to vaccination (day 0) and on day 28 (-1/+14) after vaccination. Serum Vi-Antigen IgG concentrations were measured by ELISA. Of the 85 subjects included in the per protocol data set, 45 (53%) belonged to the multiple vaccinations group. In both groups, geometric mean antibody concentrations (GMCs) were significantly higher after vaccination than before vaccination. Pre-vaccination GMCs were lower in the primary vaccination group than in the multiple vaccinations group (3.40 μg/ml versus 6.13 μg/ml, P=0.005), while there was no significant difference in the post vaccination GMCs between groups (11.34 μg/ml versus 14.58 μg/ml, P=0.4). In the multiple vaccinations group, vaccination was performed 18 to 57 months after the last vaccination (median 38 months) and there was a negative correlation between time since last vaccination and antibody concentration on day 0. In conclusion, we were not able to demonstrate a relevant immunotolerance after multiple versus primary vaccination with S. typhi Vi-capsular polysaccharide vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cost-Effectiveness Analysis of Hepatitis B Vaccination Strategies to Prevent Perinatal Transmission in North Korea: Selective Vaccination vs. Universal Vaccination

PubMed Central

Lee, Donghoon; Park, Sang Min

2016-01-01

Background To tackle the high prevalence of Hepatitis B virus (HBV) infection in North Korea, it is essential that birth doses of HBV vaccines should be administered within 24 hours of birth. As the country fails to provide a Timely Birth Dose (TBD) of HBV vaccine, the efforts of reducing the high prevalence of HBV have been significantly hampered. Methods To examine the cost-effectiveness of vaccination strategies to prevent perinatal transmission of HBV in North Korea, we established a decision tree with a Markov model consisting of selective, universal, and the country’s current vaccination program against HBV. The cost-effectiveness analysis was performed from societal and payer’s perspectives and evaluated by Disability Adjusted Life Year (DALY). Results The results suggest that introducing the universal vaccination would prevent 1,866 cases of perinatal infections per 100,000 of the birth cohort of 2013. Furthermore, 900 cases of perinatal infections per 100,000 could be additionally averted if switching to the selective vaccination. The current vaccination is a dominated strategy both from the societal and payer’s perspective. The Incremental Cost-Effectiveness Ratio (ICER) between universal and selective vaccination is $267 from the societal perspective and is reported as $273 from the payer’s perspective. Conclusion Based on the assumption that the 2012 Gross Domestic Product (GDP) per capita in North Korea, $582.6 was set for cost-effectiveness criteria, the result of this study indicates that selective vaccination may be a highly cost-effective strategy compared to universal vaccination. PMID:27802340

Timeliness of Pediatric Influenza Vaccination Compared With Seasonal Influenza Activity in an Urban Community, 2004–2008

PubMed Central

Hofstetter, Annika M.; Natarajan, Karthik; Rabinowitz, Daniel; Martinez, Raquel Andres; Vawdrey, David; Arpadi, Stephen

2013-01-01

Objectives. We assessed pediatric influenza vaccination in relation to community influenza activity. Methods. We examined seasonal influenza vaccination in 34 012 children aged 6 months through 18 years from 5 academically affiliated clinics in northern Manhattan, New York (an urban low-income community) during the 2004–2008 seasons using hospital and city immunization registries. We calculated the cumulative number of administered influenza vaccine doses and proportion of children with any (≥ 1 dose) or full (1–2 doses per age recommendations) vaccination at the onset and peak of community polymerase chain reaction–confirmed influenza activity according to state surveillance reports and by March 31 each season. Results. Influenza vaccine administration began before October 1, peaked before influenza activity onset, and declined gradually over each season. Coverage at influenza activity onset, peak, and by March 31 increased over the 5 seasons. However, most children lacked full vaccination at these time points, particularly adolescents, minorities, and those requiring 2 doses. Conclusions. Despite early initiation of influenza vaccination, few children were fully vaccinated when influenza began circulating. Interventions should address factors negatively affecting timely influenza vaccination, especially in high-risk populations. PMID:23678935

Single-cycle adenovirus vectors in the current vaccine landscape.

PubMed

Barry, Michael

2018-02-01

Traditional inactivated and protein vaccines generate strong antibodies, but struggle to generate T cell responses. Attenuated pathogen vaccines generate both, but risk causing the disease they aim to prevent. Newer gene-based vaccines drive both responses and avoid the risk of infection. While these replication-defective (RD) vaccines work well in small animals, they can be weak in humans because they do not replicate antigen genes like more potent replication-competent (RC) vaccines. RC vaccines generate substantially stronger immune responses, but also risk causing their own infections. To circumvent these problems, we developed single-cycle adenovirus (SC-Ad) vectors that amplify vaccine genes, but that avoid the risk of infection. This review will discuss these vectors and their prospects for use as vaccines. Areas covered: This review provides a background of different types of vaccines. The benefits of gene-based vaccines and their ability to replicate antigen genes are described. Adenovirus vectors are discussed and compared to other vaccine types. Replication-defective, single-cycle, and replication-competent Ad vaccines are compared. Expert commentary: The potential utility of these vaccines are discussed when used against infectious diseases and as cancer vaccines. We propose a move away from replication-defective vaccines towards more robust replication-competent or single-cycle vaccines.

Intradermal vaccination for infants and children

PubMed Central

Saitoh, Akihiko; Aizawa, Yuta

2016-01-01

ABSTRACT Intradermal (ID) vaccination induces a more potent immune response and requires lower vaccine doses as compared with standard vaccination routes. To deliver ID vaccines effectively and consistently, an ID delivery device has been developed and is commercially available for adults. The clinical application of ID vaccines for infants and children is much anticipated because children receive several vaccines, on multiple occasions, during infancy and childhood. However, experience with ID vaccines is limited and present evidence is sparse and inconsistent. ID delivery devices are not currently available for infants and children, but recent studies have examined skin thickness in this population and reported that it did not differ in proportion to body size in infants, children, and adults. These results are helpful in developing new ID devices and for preparing new vaccines in infants and children. PMID:27135736

Vaccines in a hurry.

PubMed

Søborg, Christian; Mølbak, Kåre; Doherty, T Mark; Ulleryd, Peter; Brooks, Tim; Coenen, Claudine; van der Zeijst, Ben

2009-05-26

Preparing populations for health threats, including threats from new or re-emerging infectious diseases is recognised as an important public health priority. The development, production and application of emergency vaccinations are the important measures against such threats. Vaccines are cost-effective tools to prevent disease, and emergency vaccines may be the only means to prevent a true disaster for global society in the event of a new pandemic with potential to cause morbidity and mortality comparable to the Spanish flu, the polio epidemics in the 1950s, or the SARS outbreak in 2003 if its spread had not been contained in time. Given the early recognition of a new threat, and given the advances of biotechnology, vaccinology and information systems, it is not an unrealistic goal to have promising prototype vaccine candidates available in a short time span following the identification of a new infectious agent; this is based on the assumption that the emerging infection is followed by natural immunity. However, major bottlenecks for the deployment of emergency vaccine are lack of established systems for fast-track regulatory approval of such candidates and limited international vaccine production capacity. In the present discussion paper, we propose mechanisms to facilitate development of emergency vaccines in Europe by focusing on public-private scientific partnerships, fast-track approval of emergency vaccine by regulatory agencies and proposing incentives for emergency vaccine production in private vaccine companies.

Safety and Immunogenicity of Full-Dose Trivalent Inactivated Influenza Vaccine (TIV) Compared With Half-Dose TIV Administered to Children 6 Through 35 Months of Age.

PubMed

Halasa, Natasha B; Gerber, Michael A; Berry, Andrea A; Anderson, Edwin L; Winokur, Patricia; Keyserling, Harry; Eckard, Allison Ross; Hill, Heather; Wolff, Mark C; McNeal, Monica M; Edwards, Kathryn M; Bernstein, David I

2015-09-01

Children 6 through 35 months of age are recommended to receive half the dose of influenza vaccine compared with older children and adults. This was a 6-site, randomized 2:1, double-blind study comparing full-dose (0.5 mL) trivalent inactivated influenza vaccine (TIV) with half-dose (0.25 mL) TIV in children 6 through 35 months of age. Children previously immunized with influenza vaccine (primed cohort) received 1 dose, and those with no previous influenza immunizations (naive cohort) received 2 doses of TIV. Local and systemic adverse events were recorded. Sera were collected before immunization and 1 month after last dose of TIV. Hemagglutination inhibition antibody testing was performed. Of the 243 subjects enrolled (32 primed, 211 naive), data for 232 were available for complete analysis. No significant differences in local or systemic reactions were observed. Few significant differences in immunogenicity to the 3 vaccine antigens were noted. The immune response to H1N1 was significantly higher in the full-dose group among primed subjects. In the naive cohort, the geometric mean titer for all 3 antigens after 2 doses of TIV were significantly higher in the 12 through 35 months compared with the 6 through 11 months age group. Our study confirms the safety of full-dose TIV given to children 6 through 35 months of age. An increase in antibody responses after full- versus half-dose TIV was not observed, except for H1N1 in the primed group. Larger studies are needed to clarify the potential for improved immunogenicity with higher vaccine doses. Recommending the same dose could simplify the production, storage, and administration of influenza vaccines.

Repeated Vaccination Does Not Appear to Impact Upon Influenza Vaccine Effectiveness Against Hospitalization With Confirmed Influenza.

PubMed

Cheng, Allen C; Macartney, Kristine K; Waterer, Grant W; Kotsimbos, Tom; Kelly, Paul M; Blyth, Christopher C

2017-06-01

Annual influenza vaccine is recommended for those at greatest risk of severe influenza infection. Recent reports of a negative impact of serial influenza vaccination on vaccine effectiveness (VE) raises concerns about the recommendation for annual influenza vaccines, particularly in persons at greatest risk. The Influenza Complications Alert Network (FluCAN) is an Australian hospital-based sentinel surveillance program. In this observational study, cases were defined as subjects aged >9 years admitted with influenza confirmed by polymerase chain reaction. Controls were subjects with acute respiratory illness testing negative for influenza. Propensity scores were used to adjust for the likelihood of being vaccinated. VE was calculated as 1 - adjusted odds ratio of vaccination in cases compared with test-negative controls. Over 2010-2015, 6223 cases and 6505 controls were hospitalized with confirmed influenza and influenza test-negative acute respiratory illness, respectively. Following stratification by quintile of propensity score, site, and year, VE was estimated to be 43% (95% confidence interval [CI], 37%-49%) overall. VE was estimated to be 51% (95% CI, 45%-57%) in those vaccinated in both the current and previous season, compared with 33% (95% CI, 17%-47%) vaccinated in the current season only and 35% (95% CI, 21%-46%) in the previous season only. Similar results were observed for influenza A/H1N1, influenza A/H3N2, and influenza B strains. Vaccination in both the current and previous seasons was associated with a higher VE against hospitalization with influenza than vaccination in either single season. These findings reinforce current recommendations for annual influenza vaccination, particularly those at greatest risk of influenza disease. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com

Vaccines for preventing typhoid fever.

PubMed

Milligan, Rachael; Paul, Mical; Richardson, Marty; Neuberger, Ami

2018-05-31

Typhoid fever and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and southeast Asia. Two typhoid vaccines are widely available, Ty21a (oral) and Vi polysaccharide (parenteral). Newer typhoid conjugate vaccines are at varying stages of development and use. The World Health Organization has recently recommended a Vi tetanus toxoid (Vi-TT) conjugate vaccine, Typbar-TCV, as the preferred vaccine for all ages. To assess the effects of vaccines for preventing typhoid fever. In February 2018, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, and mRCT. We also searched the reference lists of all included trials. Randomized and quasi-randomized controlled trials (RCTs) comparing typhoid fever vaccines with other typhoid fever vaccines or with an inactive agent (placebo or vaccine for a different disease) in adults and children. Human challenge studies were not eligible. Two review authors independently applied inclusion criteria and extracted data, and assessed the certainty of the evidence using the GRADE approach. We computed vaccine efficacy per year of follow-up and cumulative three-year efficacy, stratifying for vaccine type and dose. The outcome addressed was typhoid fever, defined as isolation of Salmonella enterica serovar Typhi in blood. We calculated risk ratios (RRs) and efficacy (1 - RR as a percentage) with 95% confidence intervals (CIs). In total, 18 RCTs contributed to the quantitative analysis in this review: 13 evaluated efficacy (Ty21a: 5 trials; Vi polysaccharide: 6 trials; Vi-rEPA: 1 trial; Vi-TT: 1 trial), and 9 reported on adverse events. All trials but one took place in typhoid-endemic countries. There was no information on vaccination in adults aged over 55 years of age, pregnant women, or travellers. Only one trial included data on children under two years of age.Ty21a vaccine (oral vaccine, three doses

[Benefit-risk assessment of vaccination strategies].

PubMed

Hanslik, Thomas; Boëlle, Pierre Yves

2007-04-01

This article summarises the various stages of the risk/benefit assessment of vaccination strategies. Establishing the awaited effectiveness of a vaccination strategy supposes to have an epidemiologic description of the disease to be prevented. The effectiveness of the vaccine strategy will be thus expressed in numbers of cases, hospitalizations or deaths avoided. The effectiveness can be direct, expressed as the reduction of the incidence of the infectious disease in the vaccinated subjects compared to unvaccinated subjects. It can also be indirect, the unvaccinated persons being protected by the suspension in circulation of the pathogenic agent, consecutive to the implementation of the vaccination campaign. The risks of vaccination related to the adverse effects detected during the clinical trials preceding marketing are well quantified, but other risks can occur after marketing: e.g., serious and unexpected adverse effects detected by vaccinovigilance systems, or risk of increase in the age of cases if the vaccination coverage is insufficient. The medico-economic evaluation forms a part of the risks/benefit assessment, by positioning the vaccine strategy comparatively with other interventions for health. Epidemiologic and vaccinovigilance informations must be updated very regularly, which underlines the need for having an operational and reliable real time monitoring system to accompany the vaccination strategies. Lastly, in the context of uncertainty which often accompanies the risks/benefit assessments, it is important that an adapted communication towards the public and the doctors is planned.

Reducing empiricism in malaria vaccine design.

PubMed

Moorthy, Vasee S; Kieny, Marie Paule

2010-03-01

Gains in the control of malaria and the promising progress of a malaria vaccine that is partly efficacious do not reduce the need for a high-efficacy vaccine in the longer term. Evidence supports the feasibility of developing a highly efficacious malaria vaccine. However, design of candidate malaria vaccines remains empirical and is necessarily based on many unproven assumptions because much of the knowledge needed to design vaccines and to predict efficacy is not available. Data to inform key questions of vaccine science might allow the design of vaccines to progress to a less empirical stage, for example through availability of assay results associated with vaccine efficacy. We discuss six strategic gaps in knowledge that contribute to empiricism in the design of vaccines. Comparative evaluation, assay and model standardisation, greater sharing of information, collaboration and coordination between groups, and rigorous evaluation of existing datasets are steps that can be taken to enable reductions in empiricism over time. 2010 Elsevier Ltd. All rights reserved.

The future of human DNA vaccines

PubMed Central

Li, Lei; Saade, Fadi; Petrovsky, Nikolai

2012-01-01

DNA vaccines have evolved greatly over the last 20 years since their invention, but have yet to become a competitive alternative to conventional protein or carbohydrate based human vaccines. Whilst safety concerns were an initial barrier, the Achilles heel of DNA vaccines remains their poor immunogenicity when compared to protein vaccines. A wide variety of strategies have been developed to optimize DNA vaccine immunogenicity, including codon optimization, genetic adjuvants, electroporation and sophisticated prime-boost regimens, with each of these methods having its advantages and limitations. Whilst each of these methods has contributed to incremental improvements in DNA vaccine efficacy, more is still needed if human DNA vaccines are to succeed commercially. This review foresees a final breakthrough in human DNA vaccines will come from application of the latest cutting-edge technologies, including “epigenetics” and “omics” approaches, alongside traditional techniques to improve immunogenicity such as adjuvants and electroporation, thereby overcoming the current limitations of DNA vaccines in humans PMID:22981627

The future of human DNA vaccines.

PubMed

Li, Lei; Saade, Fadi; Petrovsky, Nikolai

2012-12-31

DNA vaccines have evolved greatly over the last 20 years since their invention, but have yet to become a competitive alternative to conventional protein or carbohydrate based human vaccines. Whilst safety concerns were an initial barrier, the Achilles heel of DNA vaccines remains their poor immunogenicity when compared to protein vaccines. A wide variety of strategies have been developed to optimize DNA vaccine immunogenicity, including codon optimization, genetic adjuvants, electroporation and sophisticated prime-boost regimens, with each of these methods having its advantages and limitations. Whilst each of these methods has contributed to incremental improvements in DNA vaccine efficacy, more is still needed if human DNA vaccines are to succeed commercially. This review foresees a final breakthrough in human DNA vaccines will come from application of the latest cutting-edge technologies, including "epigenetics" and "omics" approaches, alongside traditional techniques to improve immunogenicity such as adjuvants and electroporation, thereby overcoming the current limitations of DNA vaccines in humans. Copyright © 2012 Elsevier B.V. All rights reserved.

The effects of booster vaccination on hepatitis B vaccine in anti-HBs negative infants of HBsAg-positive mothers after primary vaccination.

PubMed

Gu, Hua; Yao, Jun; Zhu, Wei; Lv, Huakun; Cheng, Suyun; Ling, Luoya; Xia, Shichang; Chen, Yongdi

2013-06-01

The purpose of this study was to investigate the changes in anti-HBs IgG levels after booster vaccinations in anti-HBs negative infants of HBsAg-positive mothers. After primary vaccination, the immunization effects of different dosages of booster vaccinations of hepatitis B vaccine (CHO) were compared. A group of 472 newborns were vaccinated with three-dose hepatitis B vaccine at birth, 1 mo and 6 mo of age. Blood serum was collected within 6-12 mo after the third dose, and HBsAg, anti-HBs and anti-HBc levels were determined. Of this group, 101 infants who were both anti-HBs and HBsAg negative were revaccinated with 20 μg hepatitis B vaccine (CHO), and their antibody titers were monitored. Among these 101 infants, the anti- HBs positive rates (defined as anti-HBs ≥ 100 mIU/ml) differed after the first and the third dose (79% and 90%, respectively (p<0.05), while differences in the corresponding geometric mean titers (GMTs) were not statistically significant (629 ± 3 mIU/ml and 572 ± 3 mIU/ml respectively, p<0.05). The anti-HBs GMTs after booster vaccination were 10-fold larger than those before booster vaccination. We conclude that a single booster dose is generally adequate for infants of HBsAg-positive mothers, whereas a further booster dose should be given for non-responders.

Vaccines for preventing herpes zoster in older adults.

PubMed

Gagliardi, Anna M Z; Gomes Silva, Brenda Nazaré; Torloni, Maria R; Soares, Bernardo G O

2012-10-17

Herpes zoster or, as it is commonly called, 'shingles' is a neurocutaneous disease characterised by the reactivation of varicella zoster virus (VZV), the virus that causes chickenpox, which is latent in the dorsal spinal ganglia when immunity to VZV declines. It is an extremely painful condition which can often last for many weeks or months, impairing the patient's quality of life. The natural aging process is associated with a reduction of cellular immunity which predisposes to herpes zoster. Vaccination with an attenuated form of VZV activates specific T cell production, therefore avoiding viral reactivation. A herpes zoster vaccine with an active virus has been approved for clinical use among older adults by the Food and Drug Administration and has been tested in large populations. To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults. We searched the following sources for relevant studies: CENTRAL 2012, Issue 7, MEDLINE (1948 to July week 1, 2012), EMBASE (2010 to July 2012), LILACS (1982 to July 2012) and CINAHL (1981 to July 2012). We also reviewed reference lists of identified trials and reviews for additional studies. Randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine with placebo or no vaccine, to prevent herpes zoster in older adults (mean age > 60 years). Two review authors independently collected and analysed data using a data extraction form. They also carried out an assessment of risk of bias. We identified eight RCTs with a total of 52,269 participants. Three studies were classified at low risk of bias. The main outcomes on effectiveness and safety were extracted from one clinical trial with a low risk of bias. Four studies compared zoster vaccine versus placebo; one study compared high-potency zoster vaccine versus low-potency zoster vaccine; one study compared refrigerated zoster vaccine versus frozen zoster vaccine; one study compared live zoster vaccine versus inactivated

Vaccinating parents experience vaccine anxiety too.

PubMed

Luthy, Karlen E; Beckstrand, Renea L; Asay, Whitney; Hewett, Carly

2013-12-01

To identify common causes of parental anxiety regarding childhood vaccinations among parents who vaccinate. Another purpose was to seek recommendations for healthcare providers to help parents overcome their anxiety when their children are immunized. Four 1-h focus groups were conducted, each consisting of 8-10 parents. Each focus group discussion was conducted by a moderator and an assistant moderator. The moderator facilitated discussion while the assistant moderator took notes. Each session was recorded on video. The data were transcribed and analyzed for themes. Parents identifying themselves as being compliant with childhood vaccination requirements reported anxiety that can be divided into five major themes: parental anxiety prior to vaccination, parental anxiety during the vaccination, parental anxiety after the vaccination, parental suggestions for healthcare providers, and informational issues. Making minor changes in office policies may help alleviate some parental anxiety regarding vaccinations. Providers should also create lists of credible sources about vaccination information. Because the cause of vaccine-related parental anxiety varies, targeted education is necessary to relieve common causes of vaccine anxiety, even among parents who vaccinate. ©2013 The Author(s) ©2013 American Association of Nurse Practitioners.

Antibody response and protective immunity of chickens vaccinated with booster dose of recombinant oil-adjuvanted Leucocytozoon caulleryi subunit vaccine.

PubMed

Umali, Dennis V; Ito, Akira; Del Valle, Fletcher P; Shirota, Kazutoshi; Katoh, Hiromitsu

2014-12-01

Leucocytozoon caulleryi is an economically important poultry pathogen that causes subclinical to fatal disease in chickens. Because of limited preventive and treatment options against this disease, an oil-adjuvanted recombinant vaccine (O-rR7) targeting the R7 protein of L. caulleryi second-generation schizonts was developed. Different vaccination programs, namely, single vaccination at 45 days (0.1-ml dose), single vaccination at 130 days (0.25 ml), and initial vaccination at 45 days (0.1 ml) followed by a booster dose at 130 days (0.25 ml) were explored to compare the effects of single and booster vaccination on antibody response, duration of protective immunity, and degree of clinical signs after experimental L. caulleryi infection. Of the three treatments groups, initial vaccination at 45 days followed by a booster vaccination at 130 days of age resulted to rapid increase in antibody titers, which persisted for up to 182 days. Antibody titers reached peak values 35 days and 14 days after initial and booster vaccination, respectively. In comparison, single vaccination at 45 days of age resulted in production of antibodies above 1600 ELISA units for 56 days postvaccination, and single vaccination at 130 days of age produced peak antibody titers 35 days postvaccination, which remained above 1600 ELISA units for 126 days. Experimental infection of L. caulleryi at 256 days, when antibody titers had waned, did not result to severe clinical disease in chickens that received booster vaccination, whereas mild to severe disease was observed in chickens that received a single vaccination. Evaluation of immune response at 15 and 21 days postinfection showed that chickens that received booster vaccination had a twofold increase (P < 0.01) in antibody titers as compared to those receiving a single vaccination. Administering booster shots of O-rR7 is therefore recommended, especially in farms located in areas where Leucocytozoon is endemic.

Evaluation of intradermal vaccination at the anti rabies vaccination OPD.

PubMed

Mankeshwar, R; Silvanus, V; Akarte, S

2014-09-01

Rabies is a virtually 100% fatal acute viral encephalitis caused by an RNA virus belonging to family Rhabdoviridae and genus Lyssavirus. The virus can infect all warm blooded animals. The disease is transmitted to humans by the bite, lick or scratch of an infected animal. More than 99% of all human rabies deaths occur in the developing world. It is preventable with timely and proper usage of modern immunobiologicals (vaccines and immunoglobulins). Once exposure occurs, modern prophylaxis entails immediate wound care, local infiltration of rabies immune globulin and parenteral administration of modern cell culture vaccines in multiple doses. The annual medicinal (vaccines and other drugs) cost for animal bite treatment is Rs. 2 billion approximately (2004). The objective of the present study is to evaluate the performance of the Intradermal (i.d.) route visa vis the Intramuscular (i.m.) route in our clinical setting the Antirabies Vaccination (ARV) OPD, Sir J.J. Hospital, Mumbai. A total of 1460 patients were administered the Antirabies vaccine by the Intradermal route over the 1 year period as compared to 1075 patients who were administered the Antirabies vaccine by the Intramuscular route in the previous year. 1230 (84.2) of the patients who were administered the vaccine by the i.d. route completed the schedule and 230 (15.8%) partially completed the schedule. Four hundred thirty two (40%) of the patients who were administered the vaccine by the Intramuscular route completed the schedule and 643 (59.8%) partially completed the schedule. The vaccine cost for i.d. was Rs. 2,80,600. The vaccine cost for the intramuscular (i.m.) assuming 84% compliance was estimated as Rs. 15, 64, 000. Assuming 40% compliance the cost was estimated as Rs. 7, 82, 230. Thus a saving of Rs. 5, 01, 630 to Rs. 12, 83, 400 was effected. In our setting, the Intradermal regime was cost effective and increased patient adherence and enrolment. It has now been routinely adopted at the clinic.

Evaluation of pneumococcal vaccination rates after vaccine protocol changes and nurse education in a tertiary care teaching hospital.

PubMed

Smith, Jennifer G; Metzger, Nicole L

2011-11-01

Pneumococcal vaccination in eligible patients is recommended by the Infectious Disease Society of America and the Centers for Disease Control (CDC) Advisory Committee on Immunization Practices. Because hospitalization provides an opportunity to vaccinate patients at high risk for developing serious pneumonia complications, eligibility screening and administration of the pneumococcal vaccine prior to discharge in qualified patients are evaluated by the Joint Commission and the Centers for Medicare Medicaid Services (CMS) as part of pneumococcal vaccination core quality measures. Among patients with an inpatient diagnosis of pneumonia in 2008, 56% in our 580-bed tertiary care teaching hospital, compared with 84% nationwide, received pneumococcal vaccination. To improve pneumococcal vaccination rates for all patients in the study facility and not just those with pneumonia, a multifaceted intervention including a revised nurse screening tool, rescheduling of the vaccine order, storage of the vaccine in automated dispensing cabinets on the nursing unit, and creation of a vaccine tracking system was developed and implemented between August 2009 and October 2009. To determine the impact of a multifaceted intervention on pneumococcal vaccine screening and administration rates in eligible patients according to the CDC recommendations who were admitted to an internal medicine unit of a tertiary care teaching hospital. All patients aged 18 years or older from 2 internal medicine units were identified during 4-month time intervals before (pre-intervention, April through July 2009) and after (post-intervention, November 2009 through February 2010) implementation of the multifaceted pneumococcal vaccine protocol. Of these, 150 patients from each 4-month period were randomly selected for electronic medical record review. Eligibility for pneumococcal vaccination was derived from the CDC recommendations and consensus of the vaccine steering committee at the study institution; the

Multiple Vaccinations: Friend or Foe

PubMed Central

Church, Sarah E.; Jensen, Shawn M.; Twitty, Chris; Bahjat, Keith; Hu, Hong-Ming; Urba, Walter J.; Fox, Bernard A.

2013-01-01

Few immunotherapists would accept the concept of a single vaccination inducing a therapeutic anti-cancer immune response in a patient with advanced cancer. But what is the evidence to support the “more-is-better” approach of multiple vaccinations? Since we are unaware of trials comparing the effect of a single vaccine versus multiple vaccinations on patient outcome, we considered that an anti-cancer immune response might provide a surrogate measure of the effectiveness of vaccination strategies. Since few large trials include immunological monitoring, the majority of information is gleaned from smaller trials in which an evaluation of immune responses to vaccine or tumor, before and at one or more times following the first vaccine was performed. In some studies there is convincing evidence that repeated administration of a specific vaccine can augment the immune response to antigens contained in the vaccine. In other settings multiple vaccinations can significantly reduce the immune response to one or more targets. Results from three large adjuvant vaccine studies support the potential detrimental effect of multiple vaccinations as clinical outcomes in the control arms were significantly better than that for treatment groups. Recent research has provided insights into mechanisms that are likely responsible for the reduced responses in the studies noted above, but supporting evidence from clinical specimens is generally lacking. Interpretation of these results is further complicated by the possibility that the dominant immune response may evolve to recognize epitopes not present in the vaccine. Nonetheless, the FDA-approval of the first therapeutic cancer vaccine and recent developments from preclinical models and clinical trials provide a substantial basis for optimism and a critical evaluation of cancer vaccine strategies. PMID:21952289

Observations on cattle schistosomiasis in the Sudan, a study in comparative medicine. III. Field testing of an irradiated Schistosoma bovis vaccine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Majid, A.A.; Bushera, H.O.; Saad, A.M.

1980-05-29

Previous work has shown that cattle can acquire a strong resistance to Schistosoma bovis infection following repeated natural exposure. Partial resistance to a laboratory challenge with S. bovis has also been demonstrated in calves after immunization with an irradiated schistosomular or cercarial vaccine. The aim of the present study was to see whether this type of caccine could protect calves under the very different conditions of natural exposure to S. bovis in the field. Thirty 6- to 9-month-old calves were each immunized with 10,000 irradiated S. bovis schistosomula by intramuscular injection and 8 weeks later were released into an enzooticmore » area along with 30 unvaccinated animals. The calves were followed up for 10 months, during which period protection was evidenced by a lower mortality rate, a slower rate of acquisition of infection, and lower fecal egg counts in the vaccinated calves. Necropsy of the survivors showed 60 to 70% reductions in worm and tissue egg counts of the vaccinated calves as compared to those not vaccinated.« less

Influence of sources of information about influenza vaccine on parental attitudes and adolescent vaccine receipt

PubMed Central

Gargano, Lisa M; Underwood, Natasha L; Sales, Jessica M; Seib, Katherine; Morfaw, Christopher; Murray, Dennis; DiClemente, Ralph J; Hughes, James M

2015-01-01

In 2011–2012, only 34% of 13–17 years olds in the United States (US) received seasonal influenza vaccine. Little is known about the link between parents' sources of health information, their vaccine-related attitudes, and vaccination of their adolescent against influenza. This study seeks to determine the relationship between number of sources of information on influenza vaccine, parental attitudes toward influenza vaccine, and influenza vaccine uptake in adolescents. We conducted a telephone and web-based survey among US parents of students enrolled in 6 middle and 5 high schools in Georgia. Bivariate and multivariable analyses were conducted to examine associations between the number of information sources about influenza vaccine and vaccine receipt and whether parent vaccine-related attitudes act as a mediator. The most commonly reported sources of information were: a physician/medical professional (95.0%), a family member or friend (80.6%), and television (77.2%). Parents who had higher attitude scores toward influenza vaccine were 5 times as likely to report their adolescent had ever received influenza vaccine compared to parents who had lower attitude scores (adjusted odds ratio (aOR) 5.1; 95% confidence intervals (CI) 3.1–8.4; P < 0.01). Parent vaccine-related attitudes were a significant mediator of the relationship between sources of information and vaccine receipt. In light of the low response rate and participation in an adolescent vaccination intervention, findings may not be generalizable to other populations. This study shows the importance of multiple sources of information in influencing parental decision-making about influenza vaccine for adolescents. Harnessing the power of mass media and family members and friends as health advocates for influenza vaccination can potentially help increase vaccination coverage of adolescents. PMID:25996686

Vaccinating Girls and Boys with Different Human Papillomavirus Vaccines: Can It Optimise Population-Level Effectiveness?

PubMed

Drolet, Mélanie; Boily, Marie-Claude; Van de Velde, Nicolas; Franco, Eduardo L; Brisson, Marc

2013-01-01

Decision-makers may consider vaccinating girls and boys with different HPV vaccines to benefit from their respective strengths; the quadrivalent (HPV4) prevents anogenital warts (AGW) whilst the bivalent (HPV2) may confer greater cross-protection. We compared, to a girls-only vaccination program with HPV4, the impact of vaccinating: 1) both genders with HPV4, and 2) boys with HPV4 and girls with HPV2. We used an individual-based transmission-dynamic model of heterosexual HPV infection and diseases. Our base-case scenario assumed lifelong efficacy of 100% against vaccine types, and 46,29,8,18,6% and 77,43,79,8,0% efficacy against HPV-31,-33,-45,-52,-58 for HPV4 and HPV2, respectively. Assuming 70% vaccination coverage and lifelong cross-protection, vaccinating boys has little additional benefit on AGW prevention, irrespective of the vaccine used for girls. Furthermore, using HPV4 for boys and HPV2 for girls produces greater incremental reductions in SCC incidence than using HPV4 for both genders (12 vs 7 percentage points). At 50% vaccination coverage, vaccinating boys produces incremental reductions in AGW of 17 percentage points if both genders are vaccinated with HPV4, but increases female incidence by 16 percentage points if girls are switched to HPV2 (heterosexual male incidence is incrementally reduced by 24 percentage points in both scenarios). Higher incremental reductions in SCC incidence are predicted when vaccinating boys with HPV4 and girls with HPV2 versus vaccinating both genders with HPV4 (16 vs 12 percentage points). Results are sensitive to vaccination coverage and the relative duration of protection of the vaccines. Vaccinating girls with HPV2 and boys with HPV4 can optimize SCC prevention if HPV2 has higher/longer cross-protection, but can increase AGW incidence if vaccination coverage is low among boys.

Comparative humoral and cellular immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18-45 years: follow-up through Month 48 in a Phase III randomized study.

PubMed

Einstein, Mark H; Levin, Myron J; Chatterjee, Archana; Chakhtoura, Nahida; Takacs, Peter; Catteau, Grégory; Dessy, Francis J; Moris, Philippe; Lin, Lan; Struyf, Frank; Dubin, Gary

2014-01-01

We previously reported higher anti-HPV-16 and -18 immune responses induced by HPV-16/18 vaccine compared with HPV-6/11/16/18 vaccine at Month 7 (one month after completion of full vaccination series) in women aged 18-45 y in an observer-blind study NCT00423046; the differences of immune response magnitudes were maintained up to Month 24. Here we report follow-up data through Month 48. At Month 48, in according-to-protocol cohort for immunogenicity (seronegative and DNA-negative for HPV type analyzed at baseline), geometric mean titers of serum neutralizing antibodies were 2.0- to 5.2-fold higher (HPV-16) and 8.6- to 12.8-fold higher (HPV-18) in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. The majority of women in both vaccine groups remained seropositive for HPV-16. The same trend was observed for HPV-18 in HPV-16/18 vaccine group; however, seropositivity rates in HPV-6/11/16/18 vaccine group decreased considerably, particularly in the older age groups. In the total vaccinated cohort (regardless of baseline serological and HPV-DNA status), anti-HPV-16 and -18 neutralizing antibody levels induced by HPV-16/18 vaccine were higher than those induced by HPV-6/11/16/18 vaccine. CD4+ T-cell response for HPV-16 and HPV-18 was higher in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. Memory B-cell responses appeared similar between vaccine groups. Both vaccines were generally well tolerated. Overall, the higher immune response observed with the HPV-16/18 vaccine was maintained up to Month 48. A head-to-head study incorporating clinical endpoints would be required to confirm whether the observed differences in immune response between the vaccines influence the duration of protection they provided.

Vaccinating high-risk children with the intranasal live-attenuated influenza vaccine: the Quebec experience.

PubMed

Quach, Caroline

2014-12-01

Given the burden of illness associated with influenza, vaccination is recommended for individuals at high risk of complications. The live-attenuated influenza vaccine (LAIV) is administered by intranasal spray, thus directly stimulating mucosal immunity. In this review, we aimed to provide evidence for its efficacy and safety in different paediatric populations. We also share the Quebec experience of LAIV use through a publicly funded vaccination program for children with chronic, high-risk conditions. from randomized controlled trials in healthy children and in asthmatics have demonstrated superior efficacy of LAIV over the injectable vaccine (IIV). LAIV is well tolerated: its administration is associated with runny nose and nasal congestion, but not with asthma exacerbations and is well tolerated in children with cystic fibrosis, when compared to IIV. The vaccine is well accepted by children and parents and can easily be part of vaccination clinics in paediatric tertiary care centres targeting children with chronic, high-risk conditions, not leading to immunosuppression. Copyright © 2014 Elsevier Ltd. All rights reserved.

Medical students' attitude towards influenza vaccination.

PubMed

Lehmann, Birthe A; Ruiter, Robert A C; Wicker, Sabine; Chapman, Gretchen; Kok, Gerjo

2015-04-15

Influenza vaccination is recommended for all healthcare personnel (HCP) and most institutions offer vaccination for free and on site. However, medical students do not always have such easy access, and the predictors that might guide the motivation of medical students to get vaccinated are largely unknown. We conducted a cross-sectional survey study among pre-clinical medical students in a German University hospital to assess the social cognitive predictors of influenza vaccination, as well as reasons for refusal and acceptance of the vaccine. Findings show that pre-clinical medical students have comparable knowledge gaps and negative attitudes towards influenza vaccination that have previously been reported among HCP. Lower injunctive norms and higher feelings of autonomy contribute to no intention to get vaccinated against influenza, while a positive instrumental attitude and higher feelings of autonomy contribute to a high intention to get vaccinated. The variables in the regression model explained 20% of the variance in intention to get vaccinated. The identified factors should be addressed early in medical education, and hospitals might benefit from a more inclusive vaccination program and accessibility of free vaccines for their medical students.

Intradermal and virosomal influenza vaccines for preventing influenza hospitalization in the elderly during the 2011-2012 influenza season: a comparative effectiveness study using the Valencia health care information system.

PubMed

Puig-Barberà, J; Natividad-Sancho, A; Calabuig-Pérez, J; Lluch-Rodrigo, J A; Pastor-Villalba, E; Martínez-Úbeda, S; Díez-Domingo, J

2014-09-22

The use of intradermal vaccination or virosomal vaccines could increase protection against influenza among the vulnerable population of older adults. Studies assessing the comparative effectiveness of these two influenza vaccine types in this age group are lacking. We conducted a retrospective cohort study to estimate the comparative effectiveness of intradermal seasonal trivalent-influenza vaccine (TIV) delivered by a microneedle injection system and a virosomal-TIV intramuscularly delivered for prevention of influenza hospitalization in non-institutionalized adults aged ≥65 years. We obtained administrative data on immunization status and influenza hospitalization for the 2011-2012 influenza season, and used Cox regression models to assess comparative effectiveness. We estimated crude and adjusted (age, sex, comorbidity, pharmaceutical claims, recent pneumococcal vaccination and number of hospitalizations for all causes other than influenza between the previous and current influenza seasons) hazard ratios (HR). Overall, 164,021 vaccinated subjects were evaluated. There were 127 hospitalizations for influenza among 62,058 subjects, contributing 914,740 person-weeks at risk in the virosomal-TIV group, and 133 hospitalizations for influenza among 101,963 subjects, contributing 1,504,570 person-weeks at risk in the intradermal-TIV group. The crude HR of intradermal-TIV relative to virosomal-TIV was 0.64 (95% confidence interval (CI): 0.50-0.81), and the adjusted Cox estimated HR was 0.67 (95% CI: 0.52-0.85). During the 2011-2012 influenza season the risk of hospitalization for influenza was reduced by 33% in non-institutionalized elderly adults who were vaccinated with intradermal-TIV compared with virosomal-TIV. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Vaccination Confidence Scale: A Brief Measure of Parents’ Vaccination Beliefs

PubMed Central

Gilkey, Melissa B.; Magnus, Brooke E.; Reiter, Paul L.; McRee, Annie-Laurie; Dempsey, Amanda F.; Brewer, Noel T.

2015-01-01

Purpose The success of national immunization programs depends on the public’s confidence in vaccines. We sought to develop a scale for measuring confidence about adolescent vaccination in diverse populations of parents. Methods Data came from 9,623 parents who completed the 2010 National Immunization Survey-Teen, an annual, population-based telephone survey. Parents reported on a 13- to 17-year-old child in their households. We used exploratory and confirmatory factor analysis to identify latent constructs underlying parents’ responses to 8 vaccination belief survey items (response scale 0–10) conceptualized using the Health Belief Model. We assessed the scale’s psychometric properties overall and across demographic subgroups. Results Parents’ confidence about adolescent vaccination was generally high. Analyses provided support for three factors assessing benefits of vaccination (mean = 8.5), harms of vaccination (mean = 3.3), and trust in healthcare providers (mean = 9.0). The model showed good fit both overall (comparative fit index = 0.97) and across demographic subgroups, although internal consistency was variable for the three factors. We found lower confidence among several potentially vulnerable subpopulations, including mothers with lower levels of education and parents whose children were of Hispanic ethnicity (both p<.05). Conclusions Our brief, three-factor scale offers an efficient way to measure confidence in adolescent vaccination across demographic subgroups. Given evidence of lower confidence by educational attainment and race/ethnicity, program planners should consider factors such as health literacy and cultural competence when designing interventions to promote adolescent vaccination to ensure these programs are fully accessible. PMID:25258098

Vaccine-induced HIV seropositivity/reactivity in noninfected HIV vaccine recipients.

PubMed

Cooper, Cristine J; Metch, Barbara; Dragavon, Joan; Coombs, Robert W; Baden, Lindsey R

2010-07-21

Induction of protective anti-human immunodeficiency virus (HIV) immune responses is the goal of an HIV vaccine. However, this may cause a reactive result in routine HIV testing in the absence of HIV infection. To evaluate the frequency of vaccine-induced seropositivity/reactivity (VISP) in HIV vaccine trial participants. Three common US Food and Drug Administration-approved enzyme immunoassay (EIA) HIV antibody kits were used to determine VISP, and a routine diagnostic HIV algorithm was used to evaluate VISP frequency in healthy, HIV-seronegative adults who completed phase 1 (n = 25) and phase 2a (n = 2) vaccine trials conducted from 2000-2010 in the United States, South America, Thailand, and Africa. Vaccine-induced seropositivity/reactivity, defined as reactive on 1 or more EIA tests and either Western blot-negative or Western blot-indeterminate/atypical positive (profile consistent with vaccine product) and HIV-1-negative by nucleic acid testing. Among 2176 participants free of HIV infection who received a vaccine product, 908 (41.7%; 95% confidence interval [CI], 39.6%-43.8%) had VISP, but the occurrence of VISP varied substantially across different HIV vaccine product types: 399 of 460 (86.7%; 95% CI, 83.3%-89.7%) adenovirus 5 product recipients, 295 of 552 (53.4%; 95% CI, 49.2%-57.7%) recipients of poxvirus alone or as a boost, and 35 of 555 (6.3%; 95% CI, 4.4%-8.7%) of DNA-alone product recipients developed VISP. Overall, the highest proportion of VISP (891/2176 tested [40.9%]) occurred with the HIV 1/2 (rDNA) EIA kit compared with the rLAV EIA (150/700 tested [21.4%]), HIV-1 Plus O Microelisa System (193/1309 tested [14.7%]), and HIV 1/2 Peptide and HIV 1/2 Plus O (189/2150 tested [8.8%]) kits. Only 17 of the 908 participants (1.9%) with VISP tested nonreactive using the HIV 1/2 (rDNA) kit. All recipients of a glycoprotein 140 vaccine (n = 70) had VISP, with 94.3% testing reactive with all 3 EIA kits tested. Among 901 participants with VISP and a Western

Human papillomavirus vaccines and vaccine implementation.

PubMed

de Sanjosé, Silvia; Alemany, Laia; Castellsagué, Xavier; Bosch, F Xavier

2008-11-01

Countries are now challenged by the rapid development of vaccines aimed at the primary prevention of infections. In the years to come, several vaccines will need to be considered as potential candidates in routine immunization programs. Recently, two new vaccines against two/four types of human papillomavirus (HPV) have been commercialized. Bivalent HPV 16 and 18 (Cervarix) and quadrivalent HPV 6, 11, 16 and 18 (Gardasil) vaccines are now extensively used in some countries. These vaccines will prevent infection and long-running complications, such as cervical cancer, other HPV-related cancers and genital warts (for the quadrivalent vaccine). The beneficial effect of these vaccines will be largely observed in women. This article summarizes the burden of HPV preventable disease worldwide and briefly describes the impact of secondary prevention and the most relevant aspects of the current available vaccines, their efficacy and safety. Finally, some major aspects that are likely to impact the introduction of these vaccines around the world are outlined, with particular emphasis on developing countries.

The value of duck-embryo vaccine and high-egg-passage Flury vaccine in experimental rabies infection in guinea-pigs

PubMed Central

Veeraraghavan, N.; Subrahmanyan, T. P.

1963-01-01

The authors have compared the value of multiple doses of duck-embryo and HEP Flury vaccine with that of pooled 5% sheep-brain vaccine in experimental rabies infection in guinea-pigs. They found that the duck-embryo vaccine given in a dosage corresponding to 14 ml of 10% vaccine (the dosage recommended for human treatment), either alone or with antirabies serum, gave no protection and that, even when administered in a dosage corresponding to 140 ml of 5% pooled vaccine, both the duck-embryo and the HEP Flury vaccines, whether alone or with serum, conferred little protection. Pooled phenolized vaccine under identical conditions gave good results. The immunogenicity of duck-embryo and HEP Flury vaccines, given before infection, was also inferior to that of pooled vaccine; and the duck-embryo vaccine was found to be a poorer antigen than the pooled vaccine in mouse potency tests. The authors conclude that the dosage of duck-embryo vaccine recommended for human treatment is inadequate and that the HEP Flury vaccine in its present form is unsuitable for post-infection treatment. PMID:14065070

Immunogenicity and safety of a combined DTaP-IPV vaccine compared with separate DTaP and IPV vaccines when administered as pre-school booster doses with a second dose of MMR vaccine to healthy children aged 4-6 years.

PubMed

Black, Steven; Friedland, Leonard R; Schuind, Anne; Howe, Barbara

2006-08-28

Combination vaccines represent one solution to the problem of increased numbers of injections during single clinic visits. A combined DTaP-IPV (Infanrix-IPV) vaccine has been developed for use as a pre-school booster. Four hundred healthy children aged 4-6 years previously primed with 4 doses of DTaP vaccine (Infanrix), 3 doses of poliovirus vaccine and 1 dose of MMR vaccine were randomized to receive single doses of either the combined DTaP-IPV vaccine or separate DTaP and IPV vaccines in a Phase II trial (DTaP-IPV-047). All children also received a second dose of MMR vaccine. Immunogenicity was assessed in serum samples taken before and 1 month after booster administration. Safety was actively assessed for 42 days post-vaccination. Non-inferiority of the DTaP-IPV vaccine to separate DTaP and IPV vaccines was demonstrated for all DTaP antigen booster response rates and poliovirus geometric mean titers of antibody ratios. Post-vaccination, > or =99.4% of children in both groups had seroprotective levels of anti-diphtheria and anti-tetanus antibodies (> or =0.1IU/mL) and seroprotective anti-poliovirus antibody titers (> or =1:8). All children in both groups were seropositive for measles, mumps and rubella antibodies, with similar post-vaccination geometric mean concentrations/titers. No significant differences were observed in the incidence of solicited local or general symptoms, unsolicited symptoms and serious adverse events between the two groups. This combined DTaP-IPV appeared safe and immunogenic when given as a booster dose at 4-6 years of age. The DTaP-IPV vaccine had no negative effect on the response to co-administered MMR vaccine, making it well-suited for use as a pre-school booster.

Effect of size and temperature at vaccination on immunization and protection conferred by a live attenuated Francisella noatunensis immersion vaccine in red hybrid tilapia.

PubMed

Soto, Esteban; Brown, Nicholas; Gardenfors, Zackarias O; Yount, Shaun; Revan, Floyd; Francis, Stewart; Kearney, Michael T; Camus, Alvin

2014-12-01

Francisella noatunensis subsp. orientalis (Fno) is a pleomorphic, facultative intracellular, Gram-negative, emerging bacterial pathogen of marine and fresh water fish with worldwide distribution. In this study, the efficacy of an attenuated Fno intracellular growth locus C (iglC) mutant was evaluated for use as a live immersion vaccine, when administered to hybrid tilapia at two different stages of growth (5 g fry and 10 g fingerlings) and at two temperatures (25 °C and 30 °C). To determine vaccine efficacy, mortality, days to first death, and Fno genome equivalents (GE) in the spleens of survivors, as well as serum and mucus antibody levels, were evaluated after 30 d in fish challenged with a wild type virulent strain. Both size and temperature at vaccination played an important role in immunization and protection. Fry vaccinated at 25 °C were not protected when compared to non-vaccinated fry at 25 °C (p = 0.870). In contrast, 5 g fry vaccinated at 30 °C were significantly protected compared to non-vaccinated fry at 30 °C (p = 0.038). Although lower mortalities occurred, 10 g fingerlings vaccinated at 25 °C were not protected, compared to non-vaccinated fingerlings at 25 °C (p = 0.328), while, 10 g fingerlings vaccinated at 30 °C were significantly protected, compared to non-vaccinated fingerlings at 30 °C (p = 0.038). Additionally, overall mortality of 5 g fish was significantly higher than in 10 g fish. Mortality was also significantly higher in fish subjected to a 30 to 25 °C temperature change one week prior to challenge, than in fish maintained at the same temperature during vaccination and challenge. This information demonstrates that both temperature and size at vaccination are important factors when implementing immunization prophylaxis in cultured tilapia.

Superior induction of T cell responses to conserved HIV-1 regions by electroporated alphavirus replicon DNA compared to that with conventional plasmid DNA vaccine.

PubMed

Knudsen, Maria L; Mbewe-Mvula, Alice; Rosario, Maximillian; Johansson, Daniel X; Kakoulidou, Maria; Bridgeman, Anne; Reyes-Sandoval, Arturo; Nicosia, Alfredo; Ljungberg, Karl; Hanke, Tomás; Liljeström, Peter

2012-04-01

Vaccination using "naked" DNA is a highly attractive strategy for induction of pathogen-specific immune responses; however, it has been only weakly immunogenic in humans. Previously, we constructed DNA-launched Semliki Forest virus replicons (DREP), which stimulate pattern recognition receptors and induce augmented immune responses. Also, in vivo electroporation was shown to enhance immune responses induced by conventional DNA vaccines. Here, we combine these two approaches and show that in vivo electroporation increases CD8(+) T cell responses induced by DREP and consequently decreases the DNA dose required to induce a response. The vaccines used in this study encode the multiclade HIV-1 T cell immunogen HIVconsv, which is currently being evaluated in clinical trials. Using intradermal delivery followed by electroporation, the DREP.HIVconsv DNA dose could be reduced to as low as 3.2 ng to elicit frequencies of HIV-1-specific CD8(+) T cells comparable to those induced by 1 μg of a conventional pTH.HIVconsv DNA vaccine, representing a 625-fold molar reduction in dose. Responses induced by both DREP.HIVconsv and pTH.HIVconsv were further increased by heterologous vaccine boosts employing modified vaccinia virus Ankara MVA.HIVconsv and attenuated chimpanzee adenovirus ChAdV63.HIVconsv. Using the same HIVconsv vaccines, the mouse observations were supported by an at least 20-fold-lower dose of DNA vaccine in rhesus macaques. These data point toward a strategy for overcoming the low immunogenicity of DNA vaccines in humans and strongly support further development of the DREP vaccine platform for clinical evaluation.

Open Reading Frame S/L of Varicella-Zoster Virus Encodes a Cytoplasmic Protein Expressed in Infected Cells

PubMed Central

Kemble, George W.; Annunziato, Paula; Lungu, Octavian; Winter, Ruth E.; Cha, Tai-An; Silverstein, Saul J.; Spaete, Richard R.

2000-01-01

We report the discovery of a novel gene in the varicella-zoster virus (VZV) genome, designated open reading frame (ORF) S/L. This gene, located at the left end of the prototype VZV genome isomer, expresses a polyadenylated mRNA containing a splice within the 3′ untranslated region in virus-infected cells. Sequence analysis reveals significant differences between the ORF S/Ls of wild-type and attenuated strains of VZV. Antisera raised to a bacterially expressed portion of ORF S/L reacted specifically with a 21-kDa protein synthesized in cells infected with a VZV clinical isolate and with the original vaccine strain of VZV (Oka-ATCC). Cells infected with other VZV strains, including a wild-type strain that has been extensively passaged in tissue culture and commercially produced vaccine strains of Oka, synthesize a family of proteins ranging in size from 21 to 30 kDa that react with the anti-ORF S/L antiserum. MeWO cells infected with recombinant VZV harboring mutations in the C-terminal region of the ORF S/L gene lost adherence to the stratum and adjacent cells, resulting in an altered plaque morphology. Immunohistochemical analysis of VZV-infected cells demonstrated that ORF S/L protein localizes to the cytoplasm. ORF S/L protein was present in skin lesions of individuals with primary or reactivated infection and in the neurons of a dorsal root ganglion during virus reactivation. PMID:11070031

Vaccine supply: a cross-national perspective.

PubMed

Danzon, Patricia M; Pereira, Nuno Sousa; Tejwani, Sapna S

2005-01-01

In U.S. vaccine markets, competing producers with high fixed, sunk costs face relatively concentrated demand. This tends to lead to exit of all but one or very few producers per vaccine. Detailed evidence of exits and shortages in the flu vaccine market demonstrates the importance of high fixed costs, demand uncertainty, and dynamic quality competition. A comparison of vaccine suppliers in four industrialized countries compared with the United States shows that smaller foreign markets often have more and different vaccine suppliers. High, country-specific, fixed costs, combined with price and volume uncertainty, plausibly deters these potential suppliers from attempting to enter the U.S. market.

Modeling the cost-effectiveness of infant vaccination with pneumococcal conjugate vaccines in Germany.

PubMed

Kuhlmann, Alexander; von der Schulenburg, J-Matthias Graf

2017-04-01

In 2009, the European Medicines Agency granted approval for two higher-valent pneumococcal conjugate vaccines. This study aims to evaluate the cost-effectiveness of universal infant (<2 years old) vaccination with a 13-valent pneumococcal conjugate vaccine (PCV13) in comparison with a 10-valent pneumococcal conjugate vaccine (PCV10) for the prevention of pneumococcal disease in Germany. A population-based Markov model was developed to estimate the impact of PCV13 and PCV10 on invasive pneumococcal disease (IPD), non-invasive pneumonia (PNE), and acute otitis media (AOM) over a time horizon of 50 years. The model included the effects of the historical vaccination scheme in infants as well as indirect herd effects and replacement disease. We used German epidemiological data to calculate episodes of IPD, PNE, and AOM, as well as direct and indirect effects of the vaccination. Parameter uncertainty was tested in univariate and probabilistic sensitivity analyses. In the base-case analysis, the ICER of PCV13 versus PCV10 infant vaccination was EUR 9826 per quality-adjusted life-year (QALY) gained or EUR 5490 per life-year (LY) gained from the societal perspective and EUR 3368 per QALY gained or EUR 1882 per LY gained from the perspective of the German statutory health insurance. The results were particularly sensitive to the magnitude of indirect effects of both vaccines. Universal infant vaccination with PCV13 is likely to be a cost-effective intervention compared with PCV10 within the German health care system, if additional net indirect effects of PCV13 vaccination are significant.

Key Facts about Seasonal Flu Vaccine

MedlinePlus

... flu illness resulting in doctor’s visits in a comparative study published in 2016. Flu vaccination is an ... illness milder if you do get sick. (For example a 2017 study showed that flu vaccination reduced ...

Meta-analysis of variables affecting mouse protection efficacy of whole organism Brucella vaccines and vaccine candidates

PubMed Central

2013-01-01

Background Vaccine protection investigation includes three processes: vaccination, pathogen challenge, and vaccine protection efficacy assessment. Many variables can affect the results of vaccine protection. Brucella, a genus of facultative intracellular bacteria, is the etiologic agent of brucellosis in humans and multiple animal species. Extensive research has been conducted in developing effective live attenuated Brucella vaccines. We hypothesized that some variables play a more important role than others in determining vaccine protective efficacy. Using Brucella vaccines and vaccine candidates as study models, this hypothesis was tested by meta-analysis of Brucella vaccine studies reported in the literature. Results Nineteen variables related to vaccine-induced protection of mice against infection with virulent brucellae were selected based on modeling investigation of the vaccine protection processes. The variable "vaccine protection efficacy" was set as a dependent variable while the other eighteen were set as independent variables. Discrete or continuous values were collected from papers for each variable of each data set. In total, 401 experimental groups were manually annotated from 74 peer-reviewed publications containing mouse protection data for live attenuated Brucella vaccines or vaccine candidates. Our ANOVA analysis indicated that nine variables contributed significantly (P-value < 0.05) to Brucella vaccine protection efficacy: vaccine strain, vaccination host (mouse) strain, vaccination dose, vaccination route, challenge pathogen strain, challenge route, challenge-killing interval, colony forming units (CFUs) in mouse spleen, and CFU reduction compared to control group. The other 10 variables (e.g., mouse age, vaccination-challenge interval, and challenge dose) were not found to be statistically significant (P-value > 0.05). The protection level of RB51 was sacrificed when the values of several variables (e.g., vaccination route, vaccine viability

Development of TV003/TV005, a single dose, highly immunogenic live attenuated dengue vaccine; what makes this vaccine different from the Sanofi-Pasteur CYD™ vaccine?

PubMed

Whitehead, Stephen S

2016-01-01

Dengue is caused by four serotype-distinct dengue viruses (DENVs), and developing a multivalent vaccine against dengue has not been straightforward since partial immunity to DENV may predispose to more severe disease upon subsequent DENV infection. The vaccine that is furthest along in development is CYD™, a live attenuated tetravalent vaccine (LATV) produced by Sanofi Pasteur. Although the multi-dose vaccine demonstrated protection against severe dengue, its overall efficacy was limited by DENV serotype, serostatus at vaccination, region and age. The National Institute of Allergy and Infectious Diseases has developed the LATV dengue vaccines TV003/TV005. A single dose of either TV003 or TV005 induced seroconversion to four DENV serotypes in 74-92% (TV003) and 90% (TV005) of flavivirus seronegative adults and elicited near-sterilizing immunity to a second dose of vaccine administered 6-12 months later. The important differences in the structure, infectivity and immune responses to TV003/TV005 are compared with CYD™.

Using a Human Challenge Model of Infection to Measure Vaccine Efficacy: A Randomised, Controlled Trial Comparing the Typhoid Vaccines M01ZH09 with Placebo and Ty21a.

PubMed

Darton, Thomas C; Jones, Claire; Blohmke, Christoph J; Waddington, Claire S; Zhou, Liqing; Peters, Anna; Haworth, Kathryn; Sie, Rebecca; Green, Christopher A; Jeppesen, Catherine A; Moore, Maria; Thompson, Ben A V; John, Tessa; Kingsley, Robert A; Yu, Ly-Mee; Voysey, Merryn; Hindle, Zoe; Lockhart, Stephen; Sztein, Marcelo B; Dougan, Gordon; Angus, Brian; Levine, Myron M; Pollard, Andrew J

2016-08-01

Typhoid persists as a major cause of global morbidity. While several licensed vaccines to prevent typhoid are available, they are of only moderate efficacy and unsuitable for use in children less than two years of age. Development of new efficacious vaccines is complicated by the human host-restriction of Salmonella enterica serovar Typhi (S. Typhi) and lack of clear correlates of protection. In this study, we aimed to evaluate the protective efficacy of a single dose of the oral vaccine candidate, M01ZH09, in susceptible volunteers by direct typhoid challenge. We performed a randomised, double-blind, placebo-controlled trial in healthy adult participants at a single centre in Oxford (UK). Participants were allocated to receive one dose of double-blinded M01ZH09 or placebo or 3-doses of open-label Ty21a. Twenty-eight days after vaccination, participants were challenged with 104CFU S. Typhi Quailes strain. The efficacy of M01ZH09 compared with placebo (primary outcome) was assessed as the percentage of participants reaching pre-defined endpoints constituting typhoid diagnosis (fever and/or bacteraemia) during the 14 days after challenge. Ninety-nine participants were randomised to receive M01ZH09 (n = 33), placebo (n = 33) or 3-doses of Ty21a (n = 33). After challenge, typhoid was diagnosed in 18/31 (58.1% [95% CI 39.1 to 75.5]) M01ZH09, 20/30 (66.7% [47.2 to 87.2]) placebo, and 13/30 (43.3% [25.5 to 62.6]) Ty21a vaccine recipients. Vaccine efficacy (VE) for one dose of M01ZH09 was 13% [95% CI -29 to 41] and 35% [-5 to 60] for 3-doses of Ty21a. Retrospective multivariable analyses demonstrated that pre-existing anti-Vi antibody significantly reduced susceptibility to infection after challenge; a 1 log increase in anti-Vi IgG resulting in a 71% decrease in the hazard ratio of typhoid diagnosis ([95% CI 30 to 88%], p = 0.006) during the 14 day challenge period. Limitations to the study included the requirement to limit the challenge period prior to treatment to 2

Vaccination status and sequence of vaccinations as risk factors for hospitalisation among outpatients in a high mortality country.

PubMed

Biai, Sidu; Rodrigues, Amabelia; Nielsen, Jens; Sodemann, Morten; Aaby, Peter

2011-05-09

Most developing countries are implementing the WHO immunisation programme. Although vaccines reach most children, many modifications of the recommended schedule are observed in practice. We investigated the association between vaccination status and risk of hospitalisation in Guinea-Bissau. From May 2003 to May 2004, all consultations of children less than five years of age at the outpatient clinic of the paediatric ward at the national hospital in Bissau were registered. For each consultation, information was collected about the child's name, sex, age and socio-cultural conditions, as well as diagnosis and whether the child was hospitalised. Information about vaccinations was also registered from the child's vaccination card. We analysed the association between vaccination status and risk of hospitalisation in age intervals according to the pre-dominant vaccines. We particularly emphasised the comparison of those who had received the recommended vaccination for the age groups and those who were delayed and only had the previous vaccinations. We also examined those who had received the vaccines out of sequence. Information about vaccinations was available for 11,949 outpatient children of whom 2219 (19%) were hospitalised. Among children less than 3 months of age, unvaccinated children compared to BCG children had as expected a higher risk of hospitalisation; controlled for important determinants of hospitalisation, the hospitalisation risk ratio (HRR) was 1.99 (95% CI 1.37-2.89). In contrast, there was no difference in the HRR for children aged 1½-8 months who were delayed and had only received BCG compared to those who as recommended had received diphtheria-tetanus-pertussis (DTP) vaccine after BCG (HRR=1.10 (0.77-1.59)). In the age interval 9-17 months of age, children who were delayed and had only received DTP had significantly higher risk of hospitalisation compared with children who as recommended had measles vaccine (MV) as the most recent vaccination (HRR

Development of Streptococcus agalactiae vaccines for tilapia.

PubMed

Liu, Guangjin; Zhu, Jielian; Chen, Kangming; Gao, Tingting; Yao, Huochun; Liu, Yongjie; Zhang, Wei; Lu, Chengping

2016-12-21

Vaccination is a widely accepted and effective method to prevent most pathogenic diseases in aquaculture. Various species of tilapia, especially Nile tilapia Oreochromis niloticus, are farmed worldwide because of their high consumer demand. Recently, the tilapia-breeding industry has been hampered by outbreaks of Streptococcus agalactiae infection, which cause high mortality and huge economic losses. Many researchers have attempted to develop effective S. agalactiae vaccines for tilapia. This review provides a summary of the different kinds of S. agalactiae vaccines for tilapia that have been developed recently. Among the various vaccine types, inactivated S. agalactiae vaccines showed superior protection efficiency when compared with live attenuated, recombinant and DNA vaccines. With respect to vaccination method, injecting the vaccine into tilapia provided the most effective immunoprotection. Freund's incomplete adjuvant appeared to be suitable for tilapia vaccines. Other factors, such as immunization duration and number, fish size and challenge dose, also influenced the vaccine efficacy.

Vaccines today, vaccines tomorrow: a perspective.

PubMed

Loucq, Christian

2013-01-01

Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles Mérieux are known among experts only despite their contribution to global health. Thanks to a vaccine, smallpox has been eradicated, polio has nearly disappeared, Haemophilus influenzae B, measles and more recently meningitis A are controlled in many countries. While a malaria vaccine is undergoing phase 3, International Vaccine Institute, in collaboration with an Indian manufacturer has brought an oral inactivated cholera vaccine to pre-qualification. The field of vaccinology has undergone major changes thanks to philanthropists such as Bill and Melinda Gates, initiatives like the Decade of Vaccines and public private partnerships. Current researches on vaccines have more challenging targets like the dengue viruses, malaria, human immunodeficiency virus, the respiratory syncytial virus and nosocomial diseases. Exciting research is taking place on new adjuvants, nanoparticles, virus like particles and new route of administration. An overcrowded infant immunization program, anti-vaccine groups, immunizing a growing number of elderlies and delivering vaccines to difficult places are among challenges faced by vaccinologists and global health experts.

Whole-cell or acellular pertussis vaccination in infancy determines IgG subclass profiles to DTaP booster vaccination.

PubMed

van der Lee, Saskia; Sanders, Elisabeth A M; Berbers, Guy A M; Buisman, Anne-Marie

2018-01-04

Duration of protection against pertussis is shorter in adolescents who have been immunized with acellular pertussis (aP) in infancy compared with adolescents who received whole-cell pertussis (wP) vaccines in infancy, which is related to immune responses elicited by these priming vaccines. To better understand differences in vaccine induced immunity, we determined pertussis, diphtheria, and tetanus (DTaP) vaccine antigen-specific IgG subclass responses in wP- and aP-primed children before and after two successive DTaP booster vaccinations. Blood samples were collected in a cross-sectional study from wP- or aP-primed children before and 1 month after the pre-school DTaP booster vaccination at age 4 years. Blood samples were collected from two different wP- and aP-primed groups of children before, 1 month and 1 year after an additional pre-adolescent Tdap booster at age 9 years. IgG subclass levels against the antigens included in the DTaP vaccine have been determined with fluorescent-bead-based multiplex immunoassays. At 4 years of age, the IgG4 proportion and concentration for pertussis, diphtheria and tetanus vaccine antigens were significantly higher in aP-primed children compared with wP-primed children. IgG4 concentrations further increased upon the two successive booster vaccinations at 4 and 9 years of age in both wP- and aP-primed children, but remained significantly higher in aP-primed children. The pertussis vaccinations administered in the primary series at infancy determine the vaccine antigen-specific IgG subclass profiles, not only against the pertussis vaccine antigens, but also against the co-administered diphtheria and tetanus vaccine antigens. These profiles did not change after DTaP booster vaccinations later in childhood. The different immune response with high proportions of specific IgG4 in some aP-primed children may contribute to a reduced protection against pertussis. ISRCTN65428640; ISRCTN64117538; NTR4089. Copyright © 2017

[Adverse effects of seasonal flu vaccine and new influenza A (H1N1) vaccine in health care workers].

PubMed

Torruella, Joan Inglés; Soto, Rosa Gil; Valls, Rosa Carreras; Lozano, Judit Valverde; Carreras, Dolors Benito; Cunillera, Arnau Besora

2013-01-01

To assess and compare adverse effects of Seasonal Influenza Vaccine (SIV) and new Influenza A(H1N1) Vaccine (AIV) in health care workers. Multicenter cross-sectional study in health care workers from acute care hospitals, primary health care centers, social centers, mental health centers and a geriatric hospital participating in the 2009 vaccination campaign. Self-administered questionnaires were sent to all workers vaccinated with SIV and/or AIV. 527 valid questionnaires were collected out of 1123 sent to SIV vaccinated workers (46.9%), and 241 out of 461 sent to AIV vaccinated workers (52.%%). Participant workers include 527 vaccinated only with SIV, 117 first vaccinated with SIV and later with AIV (SIV+AIV), and 125 vaccinated only with AIV. Overall, 18.4% (95%CI 15.1-21.7) of workers vaccinated only with SIV reported adverse effects, as compared to 45.3% (95I 36.3-54.3) reporting adverse effects to AIV in the SIV+AIV group and 46.4% (95%CI 37.7-55.1) of workers vaccinated only with AIV. In all participants the most common adverseeffect was a local reaction. Women wre more reactive to both SIV and AIV than men. In all age groups SIV vaccination alone caused fewer reactions that either AIV only or the combination of SIV+AIV, with the exception of workers below 29 years of age. AIV was associated with more reactions than SIV, with no differences observed in relation to administration sequence. There were differences by sex and age, but reactions always occurred more commonly with AIV. Copyright belongs to the Societat Catalana de Seguretat i Medicina del Treball.

Zoster Vaccine and the Risk of Postherpetic Neuralgia in Patients Who Developed Herpes Zoster Despite Having Received the Zoster Vaccine.

PubMed

Tseng, Hung Fu; Lewin, Bruno; Hales, Craig M; Sy, Lina S; Harpaz, Rafael; Bialek, Stephanie; Luo, Yi; Jacobsen, Steven J; Reddy, Kavya; Huang, Po-Yin; Zhang, Jeff; Anand, Sean; Bauer, Erin Mary; Chang, Jennifer; Tartof, Sara Y

2015-10-15

Although it is evident that zoster vaccination reduces postherpetic neuralgia (PHN) risk by reducing herpes zoster (HZ) occurrence, it is less clear whether the vaccine protects against PHN among patients who develop HZ despite previous vaccination. This cohort study included immunocompetent patients with HZ. The vaccinated cohort included 1155 individuals who were vaccinated against HZ at age ≥60 years and had an HZ episode after vaccination. Vaccinated patients were matched 1:1 by sex and age with unvaccinated patients. Trained medical residents reviewed the full medical record to determine the presence of HZ-related pain at 1, 2, 3, and 6 months after HZ diagnosis. The incidence of PHN was compared between vaccinated and unvaccinated -patients. Thirty vaccinated women (4.2%) experienced PHN, compared with 75 unvaccinated women (10.4%), with an adjusted relative risk of 0.41 (95% confidence interval, .26-.64). PHN occurred in 26 vaccinated men (6.0%) versus 25 unvaccinated men (5.8%), with an adjusted relative risk of 1.06 (.58-1.94). These associations did not differ significantly by age. Among persons experiencing HZ, prior HZ vaccination is associated with a lower risk of PHN in women but not in men. This sex-related difference may reflect differences in healthcare-seeking patterns and deserve further investigation. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Cost-effectiveness analysis of catch-up hepatitis A vaccination among unvaccinated/partially-vaccinated children

PubMed Central

Hankin-Wei, Abigail; Rein, David B.; Hernandez-Romieu, Alfonso; Kennedy, Mallory J.; Bulkow, Lisa; Rosenberg, Eli; Trigg, Monica; Nelson, Noele P.

2017-01-01

Background Since 2006, the US Centers for Disease Control and Prevention has recommended hepatitis A (HepA) vaccination routinely for children aged 12–23 months to prevent hepatitis A virus (HAV) infection. However, a substantial proportion of US children are unvaccinated and susceptible to infection. We present results of economic modeling to assess whether a one-time catch-up HepA vaccination recommendation would be cost-effective. Methods We developed a Markov model of HAV infection that followed a single cohort from birth through death (birth to age 95 years). The model compared the health and economic outcomes from catch-up vaccination interventions for children at target ages from two through 17 years vs. outcomes resulting from maintaining the current recommendation of routine vaccination at age one year with no catch-up intervention. Results Over the lifetime of the cohort, catch-up vaccination would reduce the total number of infections relative to the baseline by 741 while increasing doses of vaccine by 556,989. Catch-up vaccination would increase net costs by $10.2 million, or $2.38 per person. The incremental cost of HepA vaccine catch-up intervention at age 10 years, the midpoint of the ages modeled, was $452,239 per QALY gained. Across age-cohorts, the cost-effectiveness of catch-up vaccination is most favorable at age 12 years, resulting in an Incremental Cost-Effectiveness Ratio of $189,000 per QALY gained. Conclusions Given the low baseline of HAV disease incidence achieved by current vaccination recommendations, our economic model suggests that a catch-up vaccination recommendation would be less cost-effective than many other vaccine interventions, and that HepA catch-up vaccination would become cost effective at a threshold of $50,000 per QALY only when incidence of HAV rises about 5.0 cases per 100,000 population. PMID:27317459

Cost-effectiveness analysis of catch-up hepatitis A vaccination among unvaccinated/partially-vaccinated children.

PubMed

Hankin-Wei, Abigail; Rein, David B; Hernandez-Romieu, Alfonso; Kennedy, Mallory J; Bulkow, Lisa; Rosenberg, Eli; Trigg, Monica; Nelson, Noele P

2016-07-29

Since 2006, the US Centers for Disease Control and Prevention has recommended hepatitis A (HepA) vaccination routinely for children aged 12-23months to prevent hepatitis A virus (HAV) infection. However, a substantial proportion of US children are unvaccinated and susceptible to infection. We present results of economic modeling to assess whether a one-time catch-up HepA vaccination recommendation would be cost-effective. We developed a Markov model of HAV infection that followed a single cohort from birth through death (birth to age 95years). The model compared the health and economic outcomes from catch-up vaccination interventions for children at target ages from two through 17years vs. outcomes resulting from maintaining the current recommendation of routine vaccination at age one year with no catch-up intervention. Over the lifetime of the cohort, catch-up vaccination would reduce the total number of infections relative to the baseline by 741 while increasing doses of vaccine by 556,989. Catch-up vaccination would increase net costs by $10.2million, or $2.38 per person. The incremental cost of HepA vaccine catch-up intervention at age 10years, the midpoint of the ages modeled, was $452,239 per QALY gained. Across age-cohorts, the cost-effectiveness of catch-up vaccination is most favorable at age 12years, resulting in an Incremental Cost-Effectiveness Ratio of $189,000 per QALY gained. Given the low baseline of HAV disease incidence achieved by current vaccination recommendations, our economic model suggests that a catch-up vaccination recommendation would be less cost-effective than many other vaccine interventions, and that HepA catch-up vaccination would become cost effective at a threshold of $50,000 per QALY only when incidence of HAV rises about 5.0 cases per 100,000 population. Copyright © 2016 Elsevier Ltd. All rights reserved.

Measles-mumps-rubella-varicella combination vaccine and the risk of febrile seizures.

PubMed

Klein, Nicola P; Fireman, Bruce; Yih, W Katherine; Lewis, Edwin; Kulldorff, Martin; Ray, Paula; Baxter, Roger; Hambidge, Simon; Nordin, James; Naleway, Allison; Belongia, Edward A; Lieu, Tracy; Baggs, James; Weintraub, Eric

2010-07-01

In February 2008, we alerted the Advisory Committee on Immunization Practices to preliminary evidence of a twofold increased risk of febrile seizures after the combination measles-mumps-rubella-varicella (MMRV) vaccine when compared with separate measles-mumps-rubella (MMR) and varicella vaccines. Now with data on twice as many vaccine recipients, our goal was to reexamine seizure risk after MMRV vaccine. Using 2000-2008 Vaccine Safety Datalink data, we assessed seizures and fever visits among children aged 12 to 23 months after MMRV and separate MMR + varicella vaccines. We compared seizure risk after MMRV vaccine to that after MMR + varicella vaccines by using Poisson regression as well as with supplementary regressions that incorporated chart-review results and self-controlled analyses. MMRV vaccine recipients (83,107) were compared with recipients of MMR + varicella vaccines (376,354). Seizure and fever significantly clustered 7 to 10 days after vaccination with all measles-containing vaccines but not after varicella vaccination alone. Seizure risk during days 7 to 10 was higher after MMRV than after MMR + varicella vaccination (relative risk: 1.98 [95% confidence interval: 1.43-2.73]). Supplementary analyses yielded similar results. The excess risk for febrile seizures 7 to 10 days after MMRV compared with separate MMR + varicella vaccination was 4.3 per 10,000 doses (95% confidence interval: 2.6-5.6). Among 12- to 23-month-olds who received their first dose of measles-containing vaccine, fever and seizure were elevated 7 to 10 days after vaccination. Vaccination with MMRV results in 1 additional febrile seizure for every 2300 doses given instead of separate MMR + varicella vaccines. Providers who recommend MMRV should communicate to parents that it increases the risk of fever and seizure over that already associated with measles-containing vaccines.

Improving vaccination cold chain in the general practice setting.

PubMed

Page, Sue L; Earnest, Arul; Birden, Hudson; Deaker, Rachelle; Clark, Chris

2008-10-01

This study compared temperature control in different types of vaccine storing refrigerators in general practice and tested knowledge of general practice staff in vaccine storage requirements. Temperature data loggers were set to serially record the temperature within vaccine refrigerators in 28 general practices, recording at 12 minute intervals over a period of 10 days on each occasion. A survey of vaccine storage knowledge and records of divisions of general practice immunisation contacts were also obtained. There was a significant relationship between type of refrigerator and optimal temperature, with the odds ratio for bar style refrigerator being 0.005 (95% CI: 0.001-0.044) compared to the purpose built vaccine refrigerators. Score on a survey of vaccine storage was also positively associated with optimal storage temperature. General practices that invest in purpose built vaccine refrigerators will achieve standards of vaccine cold chain maintenance significantly more reliably than can be achieved through regular cold chain monitoring and practice supports.

Cost Description and Comparative Cost Efficiency of Post-Exposure Prophylaxis and Canine Mass Vaccination against Rabies in N'Djamena, Chad.

PubMed

Mindekem, Rolande; Lechenne, Monique Sarah; Naissengar, Kemdongarti Service; Oussiguéré, Assandi; Kebkiba, Bidjeh; Moto, Daugla Doumagoum; Alfaroukh, Idriss Oumar; Ouedraogo, Laurent Tinoanga; Salifou, Sahidou; Zinsstag, Jakob

2017-01-01

Rabies claims approximately 59,000 human lives annually and is a potential risk to 3.3 billion people in over 100 countries worldwide. Despite being fatal in almost 100% of cases, human rabies can be prevented by vaccinating dogs, the most common vector, and the timely administration of post-exposure prophylaxis (PEP) to exposed victims. For the control and prevention of human rabies in N'Djamena, the capital city of Chad, a free mass vaccination campaign for dogs was organized in 2012 and 2013. The campaigns were monitored by parallel studies on the incidence of canine rabies based on diagnostic testing of suspect animals and the incidence of human bite exposure recorded at selected health facilities. Based on the cost description of the campaign and the need for PEP registered in health centers, three cost scenarios were compared: cumulative cost-efficiency of (1) PEP alone, (2) dog mass vaccination and PEP, (3) dog mass vaccination, PEP, and maximal communication between human health and veterinary workers (One Health communication). Assuming ideal One Health communication, the cumulative prospective cost of dog vaccination and PEP break even with the cumulative prospective cost of PEP alone in the 10th year from the start of the calculation (2012). The cost efficiency expressed in cost per human exposure averted is much higher with canine vaccination and One Health communication than with PEP alone. As shown in other studies, our cost-effectiveness analysis highlights that canine vaccination is financially the best option for animal rabies control and rabies prevention in humans. This study also provides evidence of the beneficial effect of One Health communication. Only with close communication between the human and animal health sectors will the decrease in animal rabies incidence be translated into a decline for PEP. An efficiently applied One Health concept would largely reduce the cost of PEP in resource poor countries and should be implemented for

Cost Description and Comparative Cost Efficiency of Post-Exposure Prophylaxis and Canine Mass Vaccination against Rabies in N’Djamena, Chad

PubMed Central

Mindekem, Rolande; Lechenne, Monique Sarah; Naissengar, Kemdongarti Service; Oussiguéré, Assandi; Kebkiba, Bidjeh; Moto, Daugla Doumagoum; Alfaroukh, Idriss Oumar; Ouedraogo, Laurent Tinoanga; Salifou, Sahidou; Zinsstag, Jakob

2017-01-01

Rabies claims approximately 59,000 human lives annually and is a potential risk to 3.3 billion people in over 100 countries worldwide. Despite being fatal in almost 100% of cases, human rabies can be prevented by vaccinating dogs, the most common vector, and the timely administration of post-exposure prophylaxis (PEP) to exposed victims. For the control and prevention of human rabies in N’Djamena, the capital city of Chad, a free mass vaccination campaign for dogs was organized in 2012 and 2013. The campaigns were monitored by parallel studies on the incidence of canine rabies based on diagnostic testing of suspect animals and the incidence of human bite exposure recorded at selected health facilities. Based on the cost description of the campaign and the need for PEP registered in health centers, three cost scenarios were compared: cumulative cost-efficiency of (1) PEP alone, (2) dog mass vaccination and PEP, (3) dog mass vaccination, PEP, and maximal communication between human health and veterinary workers (One Health communication). Assuming ideal One Health communication, the cumulative prospective cost of dog vaccination and PEP break even with the cumulative prospective cost of PEP alone in the 10th year from the start of the calculation (2012). The cost efficiency expressed in cost per human exposure averted is much higher with canine vaccination and One Health communication than with PEP alone. As shown in other studies, our cost-effectiveness analysis highlights that canine vaccination is financially the best option for animal rabies control and rabies prevention in humans. This study also provides evidence of the beneficial effect of One Health communication. Only with close communication between the human and animal health sectors will the decrease in animal rabies incidence be translated into a decline for PEP. An efficiently applied One Health concept would largely reduce the cost of PEP in resource poor countries and should be implemented for

PubMed Central

PAGANINO, C.; TRUCCHI, C.; ALBANESE, E.; STICCHI, L.; ICARDI, G.

2015-01-01

Summary Herpes Zoster (HZ) and its main complication, post-herpetic neuralgia (PHN), represent an important public health issue because of their relevant burden within older adult population and the actual suboptimal therapeutic management of the diseases. Incidences of HZ and PHN are comparable all over the world and are closely related with the population age. Epidemiological data collected in Italy about HZ and its complications confirmed the trend registered in North America and Europe. Moreover HZ related burden is exacerbated by a significant economic impact related to both direct and indirect costs. Since 2006 a live, attenuated varicella zoster virus vaccine, that contains VZV Oka strain [Zostavax, Merck & Co., Inc.], was licensed for the prevention of HZ and PHN in adults aged ≥ 60 years. Since 2011, the licensure has been extended to adults between 50 and 59 years. The vaccine has demonstrated a good immunogenicity, efficacy and safety profiles in two pivotal phase III clinical trials and the effectiveness was further confirmed after vaccine licensure. Pharmaco-economic studies concluded that HZ vaccine is cost-effective in most European countries and generally supported the economic value of this vaccination. The vaccine is actually recommended in USA, Canada and several European countries. The opportunity to reduce the burden of these diseases by the recommendation of HZ vaccination have been evaluated and suggested also in our Country and some Regions have been recently introduced the vaccine in their immunization plan. If the good results, already obtained with HZ vaccine in other countries, will be confirmed by these Italian pilot experiences, vaccination programs should be made uniform in all Country in order to ensure an equitable offer of this important preventive tool. PMID:26789830

Field study of pneumonia in vaccinated cattle associated with incorrect vaccination and Pasteurella multocida infection.

PubMed

Crawshaw, W M; Caldow, G L

2015-04-25

This field study used data on the vaccine courses against bovine respiratory disease sold by one pharmaceutical company in conjunction with pharmacovigilance data to explore reported suspected lack of expected efficacy and the reasons for this. The study ran from May 1, 2007, to April 30, 2010, and covered vaccines sold in Scotland and part of Northumberland. In total, 83 groups of cattle reported suspected lack of expected efficacy, representing 1.6 per cent of the 804,618 vaccine courses sold. It was possible to investigate 45 of these outbreaks in depth using a standard questionnaire and diagnostic protocol. Vaccine usage outwith the specific product characteristics (SPC) occurred in 47 per cent of cases (21/45). The proportion of vaccination courses used where a pathogen contained in the vaccine was detected in the diseased cattle and vaccine use was consistent with the SPC was estimated at 0.12 per cent of the courses sold. Pasteurella multocida was the most common pathogen detected and was found in 21 of the outbreaks. For outbreaks where a pathogen contained in the vaccine was detected, P. multocida was found at a significantly greater frequency (P=0.03) where vaccine use was compliant with the SPC (five of six outbreaks) compared with outbreaks where vaccine use had not been compliant with the SPC (one of seven outbreaks). The limitations of the study, including the diagnostic tests employed and definition of vaccination outwith the SPC, are discussed. British Veterinary Association.

[Comparative evaluation of Leningrad-3 mumps vaccine virus neurovirulence in a neonatal rat model].

PubMed

Ignat'ev, G M; Otrashevskaia, E V; Rubin, S A

2011-01-01

The neurovirulence and replication potential of several mumps virus strains, including Leningrad-3 mumps vaccine virus (FSUE SIC "Microgen", Russia) and wild type strains isolated in the Novosibirsk Region (Russia), were assessed in rat tests. The mean neurovirulence scores of the Leningrad-3 virus (< 4.0) were significantly lower than those of wild type strains (ranging from 6.1 to 15.2) and were in accordance with the scores determined for other attenuated mumps vaccine strains (usually ranging from 0 to 5). In general, the relative ability of the viruses to replicate in the rat brain tracked with their neurovirulence scores. These results indicate a low neurovirulence potential of the Leningrad-3 mumps vaccine virus for humans.

Influenza vaccine response profiles are affected by vaccine preparation and preexisting immunity, but not HIV infection.

PubMed

Berger, Christoph T; Greiff, Victor; Mehling, Matthias; Fritz, Stefanie; Meier, Marc A; Hoenger, Gideon; Conen, Anna; Recher, Mike; Battegay, Manuel; Reddy, Sai T; Hess, Christoph

2015-01-01

Vaccines dramatically reduce infection-related morbidity and mortality. Determining factors that modulate the host response is key to rational vaccine design and demands unsupervised analysis. To longitudinally resolve influenza-specific humoral immune response dynamics we constructed vaccine response profiles of influenza A- and B-specific IgM and IgG levels from 42 healthy and 31 HIV infected influenza-vaccinated individuals. Pre-vaccination antibody levels and levels at 3 predefined time points after vaccination were included in each profile. We performed hierarchical clustering on these profiles to study the extent to which HIV infection associated immune dysfunction, adaptive immune factors (pre-existing influenza-specific antibodies, T cell responses), an innate immune factor (Mannose Binding Lectin, MBL), demographic characteristics (gender, age), or the vaccine preparation (split vs. virosomal) impacted the immune response to influenza vaccination. Hierarchical clustering associated vaccine preparation and pre-existing IgG levels with the profiles of healthy individuals. In contrast to previous in vitro and animal data, MBL levels had no impact on the adaptive vaccine response. Importantly, while HIV infected subjects with low CD4 T cell counts showed a reduced magnitude of their vaccine response, their response profiles were indistinguishable from those of healthy controls, suggesting quantitative but not qualitative deficits. Unsupervised profile-based analysis ranks factors impacting the vaccine-response by relative importance, with substantial implications for comparing, designing and improving vaccine preparations and strategies. Profile similarity between HIV infected and HIV negative individuals suggests merely quantitative differences in the vaccine response in these individuals, offering a rationale for boosting strategies in the HIV infected population.

A proposed framework for evaluating and comparing efficacy estimates in clinical trials of new rotavirus vaccines.

PubMed

Neuzil, Kathleen M; Zaman, K; Victor, John C

2014-08-11

Oral rotavirus vaccines have yielded different point estimates of efficacy when tested in different populations. While population and environmental factors may account for these differences, study design characteristics should also be considered. We review the study design elements of rotavirus vaccine trials that may affect point estimates of efficacy, and propose a framework for evaluating new rotavirus vaccines. Copyright © 2014. Published by Elsevier Ltd.

Assessing the Importance of Domestic Vaccine Manufacturing Centers: An Overview of Immunization Programs, Vaccine Manufacture, and Distribution.

PubMed

Rey-Jurado, Emma; Tapia, Felipe; Muñoz-Durango, Natalia; Lay, Margarita K; Carreño, Leandro J; Riedel, Claudia A; Bueno, Susan M; Genzel, Yvonne; Kalergis, Alexis M

2018-01-01

Vaccines have significantly reduced the detrimental effects of numerous human infectious diseases worldwide, helped to reduce drastically child mortality rates and even achieved eradication of major pathogens, such as smallpox. These achievements have been possible due to a dedicated effort for vaccine research and development, as well as an effective transfer of these vaccines to public health care systems globally. Either public or private institutions have committed to developing and manufacturing vaccines for local or international population supply. However, current vaccine manufacturers worldwide might not be able to guarantee sufficient vaccine supplies for all nations when epidemics or pandemics events could take place. Currently, different countries produce their own vaccine supplies under Good Manufacturing Practices, which include the USA, Canada, China, India, some nations in Europe and South America, such as Germany, the Netherlands, Italy, France, Argentina, and Brazil, respectively. Here, we discuss some of the vaccine programs and manufacturing capacities, comparing the current models of vaccine management between industrialized and developing countries. Because local vaccine production undoubtedly provides significant benefits for the respective population, the manufacture capacity of these prophylactic products should be included in every country as a matter of national safety.

Assessing the Importance of Domestic Vaccine Manufacturing Centers: An Overview of Immunization Programs, Vaccine Manufacture, and Distribution

PubMed Central

Rey-Jurado, Emma; Tapia, Felipe; Muñoz-Durango, Natalia; Lay, Margarita K.; Carreño, Leandro J.; Riedel, Claudia A.; Bueno, Susan M.; Genzel, Yvonne; Kalergis, Alexis M.

2018-01-01

Vaccines have significantly reduced the detrimental effects of numerous human infectious diseases worldwide, helped to reduce drastically child mortality rates and even achieved eradication of major pathogens, such as smallpox. These achievements have been possible due to a dedicated effort for vaccine research and development, as well as an effective transfer of these vaccines to public health care systems globally. Either public or private institutions have committed to developing and manufacturing vaccines for local or international population supply. However, current vaccine manufacturers worldwide might not be able to guarantee sufficient vaccine supplies for all nations when epidemics or pandemics events could take place. Currently, different countries produce their own vaccine supplies under Good Manufacturing Practices, which include the USA, Canada, China, India, some nations in Europe and South America, such as Germany, the Netherlands, Italy, France, Argentina, and Brazil, respectively. Here, we discuss some of the vaccine programs and manufacturing capacities, comparing the current models of vaccine management between industrialized and developing countries. Because local vaccine production undoubtedly provides significant benefits for the respective population, the manufacture capacity of these prophylactic products should be included in every country as a matter of national safety. PMID:29403503

Daily versus single-day offering of influenza vaccine in community pharmacies.

PubMed

Grabenstein, John D

2009-01-01

To assess the cumulative number of influenza vaccinations delivered per pharmacy in relation to number of days of offering vaccination per season. Automated records of pharmacies involved in a cohort study were queried for number of influenza vaccinations delivered in each of three influenza vaccination seasons between 1996 and 1998. Eleven pharmacies in Washington State were compared with 13 pharmacies in Oregon, contrasting years when nurses offered influenza vaccine 1 day per season with years when pharmacists offered influenza vaccine daily for several months. Pharmacies in which pharmacists offered influenza vaccination daily averaged 528 to 807 doses per pharmacy per season compared with 91 to 233 doses per pharmacy in seasons when nurses offered vaccination on a single day. Professionals dedicated to providing adult vaccination on any given day outperformed professionals who attended to both vaccination and other clinical duties, but the cumulative effect of offering vaccinations on multiple days can achieve a greater number of vaccinations over a several-month interval.

Vaccination with Haemophilus influenzae type b conjugate vaccine reduces bacterial meningitis in Morocco.

PubMed

Braikat, Mohamed; Barkia, Abdelaziz; El Mdaghri, Naima; Rainey, Jeanette J; Cohen, Adam L; Teleb, Nadia

2012-03-28

Haemophilus influenzae type b (Hib) is a leading cause of bacterial meningitis and pneumonia and can be prevented by Hib vaccine. We conducted a vaccine impact evaluation to support continued use of Hib vaccine in Morocco following introduction in 2007. Bacterial meningitis surveillance data from 2004 to 2009 were obtained from 11 sentinel hospitals located in eight provinces and one prefecture in Morocco to examine Hi meningitis reporting for cases aged <5 years. We defined the years of 2004-2006 as the pre-vaccine period and 2008-2009 as the post-vaccine period and compared the mean annual number of confirmed Hi meningitis cases for these time periods using a Chi-square test. We calculated the minimum incidence of Hi meningitis during the evaluation period in Grand Casa Prefecture, where the catchment population could be estimated. From 2004 to 2009, 1844 suspected meningitis case-patients aged <5 years were reported; 354 (19.2%) were confirmed with bacterial meningitis, including 105 (29.7%) Hi cases. The mean annual number of confirmed Hi meningitis cases decreased by 75%, from 24 in the pre-vaccine period to 6 during the post-vaccine period (p<0.001). Assuming Hi cases with unknown age were <5 years of age, the estimated minimum incidence of confirmed Hi meningitis in Grand Casa Prefecture decreased by 93%, from 15 cases per 100,000 children in the pre-vaccine period to 1 case per 100,000 children in the post-vaccine period. Hib vaccine introduction likely significantly reduced the occurrence of Hi meningitis among children aged <5 years at the 11 sentinel hospitals included in this evaluation in Morocco, suggesting that continued use of Hib vaccine in Morocco would be beneficial. Published by Elsevier Ltd.

Footrot vaccines and vaccination.

PubMed

Dhungyel, Om; Hunter, James; Whittington, Richard

2014-05-30

Research on footrot in small ruminants, which is caused by Dichelobacter nodosus, has led to development of vaccines and their application for control, treatment and eradication of the disease in sheep. Footrot vaccines have evolved over decades to contain monovalent whole cell, multivalent recombinant fimbrial, and finally mono or bivalent recombinant fimbrial antigens. Initially whole cell vaccines made against the few known serogroups of D. nodosus were found to be inefficient in control of the disease in the field, which was attributed to the presence of other unidentified serogroups and also the use of inefficient adjuvants. Fimbriae or pili, which are the basis for antigenic variation, were found to be the major protective and also curative antigens but they are not cross protective between the different serogroups. Multivalent vaccines incorporating all the known serogroups have been proven to be of limited efficacy due to the phenomenon of antigenic competition. Recent studies in Nepal, Bhutan and Australia have shown that outbreak-specific vaccination which involves targeting identified serogroups with mono- or bivalent recombinant fimbrial vaccines, can be very effective in sheep and goats. Where multiple serogroups are present in a flock, antigenic competition can be overcome by sequentially targeting the serogroups with different bivalent vaccines every 3 months. A common antigen which would confer immunity to all serogroups would be the ideal immunogen but the initial studies were not successful in this area. Until universal antigen/s are available, flock specific mono or bivalent fimbrial vaccines are likely to be the most effective tool for control and eradication of footrot in sheep and goats. Future research in footrot vaccines should be focused on improving the duration of prophylaxis by incorporating new and emerging immunomodulators or adjuvants with modified delivery vehicles, discovering a common antigen and understanding the mechanisms of

Comparative Efficacy of Hemagglutinin, Nucleoprotein, and Matrix 2 Protein Gene-Based Vaccination against H5N1 Influenza in Mouse and Ferret

PubMed Central

Rao, Srinivas S.; Kong, Wing-Pui; Wei, Chih-Jen; Van Hoeven, Neal; Gorres, J. Patrick; Nason, Martha; Andersen, Hanne; Tumpey, Terrence M.; Nabel, Gary J.

2010-01-01

Efforts to develop a broadly protective vaccine against the highly pathogenic avian influenza A (HPAI) H5N1 virus have focused on highly conserved influenza gene products. The viral nucleoprotein (NP) and ion channel matrix protein (M2) are highly conserved among different strains and various influenza A subtypes. Here, we investigate the relative efficacy of NP and M2 compared to HA in protecting against HPAI H5N1 virus. In mice, previous studies have shown that vaccination with NP and M2 in recombinant DNA and/or adenovirus vectors or with adjuvants confers protection against lethal challenge in the absence of HA. However, we find that the protective efficacy of NP and M2 diminishes as the virulence and dose of the challenge virus are increased. To explore this question in a model relevant to human disease, ferrets were immunized with DNA/rAd5 vaccines encoding NP, M2, HA, NP+M2 or HA+NP+M2. Only HA or HA+NP+M2 vaccination conferred protection against a stringent virus challenge. Therefore, while gene-based vaccination with NP and M2 may provide moderate levels of protection against low challenge doses, it is insufficient to confer protective immunity against high challenge doses of H5N1 in ferrets. These immunogens may require combinatorial vaccination with HA, which confers protection even against very high doses of lethal viral challenge. PMID:20352112

A Randomized Phase II Study of Concurrent Docetaxel Plus Vaccine Versus Vaccine Alone in Metastatic Androgen Independent Prostate Cancer

PubMed Central

Arlen, Philip M.; Gulley, James L.; Parker, Catherine; Skarupa, Lisa; Pazdur, Mary; Panicali, Dennis; Beetham, Patricia; Tsang, Kwong Y.; Grosenbach, Douglas W.; Feldman, Jarett; Steinberg, Seth M.; Jones, Elizabeth; Chen, Clara; Marte, Jennifer; Schlom, Jeffrey; Dahut, William

2006-01-01

Purpose: Docetaxel has activity against androgen insensitive prostate cancer (AIPC) and preclinical studies have demonstrated that taxane-based chemotherapy can enhance antitumor response of vaccines. The primary objective of this study was to determine if concurrent docetaxel (with dexamethasone) had any effect on generating an immune response to the vaccine. Secondary endpoints were whether vaccine could be given safely with docetaxel and the clinical outcome of the treatment regimen. Experimental Design: The vaccination regimen was composed of (1) recombinant vaccinia virus (rV) that expresses the prostate-specific antigen gene (rV-PSA) admixed with (2) rV that expresses the B7.1 costimulatory gene (rV-B7.1), and (3) sequential booster vaccinations with recombinant fowlpox virus (rF-) containing the PSA gene (rF- PSA). Patients received GM-CSF with each vaccination. Twenty-eight patients with metastatic AIPC were randomized to receive either vaccine and weekly docetaxel or vaccine alone. Patients on the vaccine alone arm were allowed to cross over to receive docetaxel alone at time of disease progression. The ELISPOT assay was used to monitor immune responses for PSA-specific T cells. Results: The median increase in these T-cell precursors to PSA was 3.33-fold in both arms following 3 months of therapy. In addition, immune responses to other prostate cancer associated tumor antigens were also detected post-vaccination. Eleven patients who progressed on vaccine alone crossed over to receive docetaxel at time of progression. Median PFS on docetaxel was 6.1 months after receiving vaccine compared with 3.7 months with the same regimen in a historical control. Conclusion: This is the first clinical trial to demonstrate that docetaxel can be administered safely with immunotherapy without inhibiting vaccine specific T-cell responses. Furthermore, patients previously vaccinated with an anticancer vaccine may respond longer to docetaxel compared with a historical control

Smallpox vaccines: targets of protective immunity

PubMed Central

Moss, Bernard

2011-01-01

Summary The eradication of smallpox, one of the great triumphs of medicine, was accomplished through the prophylactic administration of live vaccinia virus, a comparatively benign relative of variola virus, the causative agent of smallpox. Nevertheless, recent fears that variola virus may be used as a biological weapon together with the present susceptibility of unimmunized populations have spurred the development of new generation vaccines that are safer than the original and can be produced by modern methods. Predicting the efficacy of such vaccines in the absence of human smallpox, however, depends on understanding the correlates of protection. This review outlines the biology of poxviruses with particular relevance to vaccine development, describes protein targets of humoral and cellular immunity, compares animal models of orthopoxvirus disease with human smallpox, and considers the status of second and third generation smallpox vaccines. PMID:21198662

Validation of the Vaccination Confidence Scale: A brief measure to identify parents at risk for refusing adolescent vaccines

PubMed Central

Reiter, Paul L.; Magnus, Brooke E.; McRee, Annie-Laurie; Dempsey, Amanda F.; Brewer, Noel T.

2015-01-01

Objective To support efforts to address vaccine hesitancy, we sought to validate a brief measure of vaccination confidence using a large, nationally representative sample of parents. Methods We analyzed weighted data from 9,018 parents who completed the 2010 National Immunization Survey-Teen, an annual, population-based telephone survey. Parents reported on the immunization history of a 13- to 17-year-old child in their households for vaccines including tetanus, diphtheria, and acellular pertussis (Tdap), meningococcal, and human papillomavirus (HPV) vaccines. For each vaccine, separate logistic regression models assessed associations between parents’ mean scores on the 8-item Vaccination Confidence Scale and vaccine refusal, vaccine delay, and vaccination status. We repeated analyses for the scale’s 4-item short form. Results One quarter of parents (24%) reported refusal of any vaccine, with refusal of specific vaccines ranging from 21% for HPV to 2% for Tdap. Using the full 8-item scale, vaccination confidence was negatively associated with measures of vaccine refusal and positively associated with measures of vaccination status. For example, refusal of any vaccine was more common among parents whose scale scores were medium (odds ratio [OR] = 2.08, 95% confidence interval [CI], 1.75–2.47) or low (OR = 4.61, 95% CI, 3.51–6.05) versus high. For the 4-item short form, scores were also consistently associated with vaccine refusal and vaccination status. Vaccination confidence was inconsistently associated with vaccine delay. Conclusions The Vaccination Confidence Scale shows promise as a tool for identifying parents at risk for refusing adolescent vaccines. The scale’s short form appears to offer comparable performance. PMID:26300368