A novel therapeutic hepatitis B vaccine induces cellular and humoral immune responses and breaks tolerance in hepatitis B virus (HBV) transgenic mice.

PubMed

Buchmann, Pascale; Dembek, Claudia; Kuklick, Larissa; Jäger, Clemens; Tedjokusumo, Raindy; von Freyend, Miriam John; Drebber, Uta; Janowicz, Zbigniew; Melber, Karl; Protzer, Ulrike

2013-02-06

Therapeutic vaccines are currently being developed for chronic hepatitis B and C. As an alternative to long-term antiviral treatment or to support only partially effective therapy, they should activate the patient's immune system effectively to fight and finally control the virus. A paradigm of therapeutic vaccination is the potent induction of T-cell responses against key viral antigens - besides activation of a humoral immune response. We have evaluated the potential of a novel vaccine formulation comprising particulate hepatitis B surface (HBsAg) and core antigen (HBcAg), and the saponin-based ISCOMATRIX™ adjuvant for its ability to stimulate T and B cell responses in C57BL/6 mice and its ability to break tolerance in syngeneic HBV transgenic (HBVtg) mice. In C57BL/6 mice, the vaccine induced multifunctional HBsAg- and HBcAg-specific CD8+ T cells detected by staining for IFNγ, TNFα and IL-2, as well as high antibody titers against both antigens. Vaccination of HBVtg animals induced potent HBsAg- and HBcAg-specific CD8+ T-cell responses in spleens and HBcAg-specific CD8+ T-cell responses in livers as well as anti-HBs seroconversion two weeks post injection. Vaccination further reduced HBcAg expression in livers of HBVtg mice without causing liver damage. In summary, this study demonstrates therapeutic efficacy of a novel vaccine formulation in a mouse model of immunotolerant, chronic HBV infection. Copyright © 2013 Elsevier Ltd. All rights reserved.

Protective efficacy of recombinant BCG Tokyo (Ag85A) in rhesus monkeys (Macaca mulatta) infected intratracheally with H37Rv Mycobacterium tuberculosis.

PubMed

Sugawara, I; Sun, L; Mizuno, S; Taniyama, T

2009-01-01

We have reported previously that recombinant BCG Tokyo (Ag85A) (rBCG-Ag85A[Tokyo]) shows promise as a tuberculosis vaccine, demonstrating protective efficacy in cynomolgus monkeys. As a next step, rhesus monkeys were utilized because they are also susceptible to Mycobacterium tuberculosis and show a continuous course of infection resembling human tuberculosis. The recombinant BCG vaccine (5x10(5) CFU per monkey) was administered once intradermally into the back skin to three groups of rhesus monkeys, and its protective efficacy was compared for 4months with that of its parental BCG Tokyo strain. Eight week vaccination of the monkeys with rBCG-Ag85A[Tokyo] resulted in a reduction of tubercle bacilli CFU (p<0.01) and lung pathology in animals infected intratracheally with 3000 CFU H37Rv M. tuberculosis. Vaccination prevented an increase in the old tuberculin test after challenge with M. tuberculosis and reaction of M. tuberculosis-derived antigen. Thus, it was shown that even in rhesus monkeys rBCG-Ag85A[Tokyo] induced higher protective efficacy than BCG Tokyo.

A first-in-human phase 1 trial to evaluate the safety and immunogenicity of the candidate tuberculosis vaccine MVA85A-IMX313, administered to BCG-vaccinated adults

PubMed Central

Minhinnick, Alice; Satti, Iman; Harris, Stephanie; Wilkie, Morven; Sheehan, Sharon; Stockdale, Lisa; Thomas, Zita-Rose Manjaly; Lopez-Ramon, Raquel; Poulton, Ian; Lawrie, Alison; Vermaak, Samantha; Le Vert, Alexandre; Del Campo, Judith; Hill, Fergal; Moss, Paul; McShane, Helen

2016-01-01

Introduction There is an urgent need for a new and effective tuberculosis vaccine because BCG does not sufficiently prevent pulmonary disease. IMX313 is a novel carrier protein designed to improve cellular and humoral immunity. MVA85A-IMX313 is a novel vaccine candidate designed to boost immunity primed by bacillus Calmette-Guérin (BCG) that has been immunogenic in pre-clinical studies. This is the first evaluation of IMX313 delivered as MVA85A-IMX313 in humans. Methods In this phase 1, open-label first-in-human trial, 30 healthy previously BCG-vaccinated adults were enrolled into three treatment groups and vaccinated with low dose MVA85A-IMX313 (group A), standard dose MVA85A-IMX313 (group B), or MVA85A (group C). Volunteers were followed up for 6 months for safety and immunogenicity assessment. Results The majority of adverse events were mild and there were no vaccine-related serious AEs. Both MVA85A-IMX313 and MVA85A induced a significant increase in IFN-γ ELISpot responses. There were no significant differences between the Ag85A ELISpot and intracellular cytokine responses between the two study groups B (MVA85A-IMX313) and C (MVA85A) at any time point post-vaccination. Conclusion MVA85A-IMX313 was well tolerated and immunogenic. There was no significant difference in the number of vaccine-related, local or systemic adverse reactions between MVA85A and MVA85A-IMX313 groups. The mycobacteria-specific cellular immune responses induced by MVA85A-IMX313 were not significantly different to those detected in the MVA85A group. In light of this encouraging safety data, further work to improve the potency of molecular adjuvants like IMX313 is merited. This trial was registered on clinicatrials.gov ref. NCT01879163. PMID:26854906

Loss of confidence in vaccines following media reports of infant deaths after hepatitis B vaccination in China.

PubMed

Yu, Wenzhou; Liu, Dawei; Zheng, Jingshan; Liu, Yanmin; An, Zhijie; Rodewald, Lance; Zhang, Guomin; Su, Qiru; Li, Keli; Xu, Disha; Wang, Fuzhen; Yuan, Ping; Xia, Wei; Ning, Guijun; Zheng, Hui; Chu, Yaozhu; Cui, Jian; Duan, Mengjuan; Hao, Lixin; Zhou, Yuqing; Wu, Zhenhua; Zhang, Xuan; Cui, Fuqiang; Li, Li; Wang, Huaqing

2016-04-01

China reduced hepatitis B virus (HBV) infection by 90% among children under 5 years old with safe and effective hepatitis B vaccines (HepB). In December 2013, this success was threatened by widespread media reports of infant deaths following HepB administration. Seventeen deaths and one case of anaphylactic shock following HBV vaccination had been reported. We conducted a telephone survey to measure parental confidence in HepB in eleven provinces at four points in time; reviewed maternal HBV status and use of HepB for newborns in birth hospitals in eight provinces before and after the event; and monitored coverage with hepatitis B vaccine and other programme vaccines in ten provinces. HepB from the implicated company was suspended during the investigation, which showed that the deaths were not caused by HepB vaccination. Before the event, 85% respondents regarded domestic vaccines as safe, decreasing to 26.7% during the event. During the height of the crisis, 30% of parents reported being hesitant to vaccinate and 18.4% reported they would refuse HepB. Use of HepB in the monitored provinces decreased by 18.6%, from 53 653 doses the week before the event to 43 688 doses during the week that Biokangtai HepB was suspended. Use of HepB within the first day of life decreased by 10% among infants born to HBsAg-negative mothers, and by 6% among infants born to HBsAg-positive mothers. Vaccine refusal and HepB birth dose rates returned to baseline within 2 months; confidence increased, but remained below baseline. The HBV vaccine event resulted in the suspension of a safe vaccine, which was associated with a decline of parental confidence, and refusal of vaccination. Suspension of a vaccine can lead to loss of confidence that is difficult to recover. Timely and credible investigation, accompanied by proactive outreach to stakeholders and the media, may help mitigate negative impact of future coincidental adverse events following immunization. © The Author 2016; all rights

Improvement of BCG protective efficacy with a novel chimpanzee adenovirus and a modified vaccinia Ankara virus both expressing Ag85A.

PubMed

Stylianou, E; Griffiths, K L; Poyntz, H C; Harrington-Kandt, R; Dicks, M D; Stockdale, L; Betts, G; McShane, H

2015-11-27

A replication-deficient chimpanzee adenovirus expressing Ag85A (ChAdOx1.85A) was assessed, both alone and in combination with modified vaccinia Ankara also expressing Ag85A (MVA85A), for its immunogenicity and protective efficacy against a Mycobacterium tuberculosis (M.tb) challenge in mice. Naïve and BCG-primed mice were vaccinated or boosted with ChAdOx1.85A and MVA85A in different combinations. Although intranasally administered ChAdOx1.85A induced strong immune responses in the lungs, it failed to consistently protect against aerosol M.tb challenge. In contrast, ChAdOx1.85A followed by MVA85A administered either mucosally or systemically, induced strong immune responses and was able to improve the protective efficacy of BCG. This vaccination regime has consistently shown superior protection over BCG alone and should be evaluated further. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Hepatitis B virus surface antigen (HBsAg)-positive and HBsAg-negative hepatitis B virus infection among mother-teenager pairs 13 years after neonatal hepatitis B virus vaccination.

PubMed

Yao, Qing-Qing; Dong, Xiao-Lian; Wang, Xue-Cai; Ge, Sheng-Xiang; Hu, An-Qun; Liu, Hai-Yan; Wang, Yueping Alex; Yuan, Quan; Zheng, Ying-Jie

2013-02-01

It is unclear whether a mother who is negative for hepatitis B virus surface antigen (HBsAg) but positive for hepatitis B virus (HBV) is at potential risk for mother-to-child transmission of HBV. This study, using a paired mother-teenager population, aimed to assess whether maternal HBsAg-negative HBV infection ((hn)HBI) is a significant source of child HBV infection (HBI). A follow-up study with blood collection has been conducted on the 93 mother-teenager pairs from the initial 135 pregnant woman-newborn pairs 13 years after neonatal HBV vaccination. Serological and viral markers of HBV have been tested, and phylogenetic analysis of HBV isolates has been done. The HBI prevalence was 1.9% (1 (hn)HBI/53) for teenage children of non-HBI mothers, compared with 16.7% (1 (hn)HBI/6) for those of (hn)HBI mothers and 2.9% (1 HBsAg-positive HBV infection [(hp)HBI]/34) for those of (hp)HBI mothers. Similar viral sequences have been found in one pair of whom both the mother and teenager have had (hn)HBI. In comparison with the (hp)HBI cases, those with (hn)HBI had a lower level of HBV load and a higher proportion of genotype-C strains, which were accompanied by differentiated mutations (Q129R, K141E, and Y161N) of the "a" determinant of the HBV surface gene. Our findings suggest that mother-to-teenager transmission of (hn)HBI can occur among those in the neonatal HBV vaccination program.

Hepatitis B Virus Surface Antigen (HBsAg)-Positive and HBsAg-Negative Hepatitis B Virus Infection among Mother-Teenager Pairs 13 Years after Neonatal Hepatitis B Virus Vaccination

PubMed Central

Yao, Qing-Qing; Dong, Xiao-Lian; Wang, Xue-Cai; Ge, Sheng-Xiang; Hu, An-Qun; Liu, Hai-Yan; Wang, Yueping Alex

2013-01-01

It is unclear whether a mother who is negative for hepatitis B virus surface antigen (HBsAg) but positive for hepatitis B virus (HBV) is at potential risk for mother-to-child transmission of HBV. This study, using a paired mother-teenager population, aimed to assess whether maternal HBsAg-negative HBV infection (hnHBI) is a significant source of child HBV infection (HBI). A follow-up study with blood collection has been conducted on the 93 mother-teenager pairs from the initial 135 pregnant woman-newborn pairs 13 years after neonatal HBV vaccination. Serological and viral markers of HBV have been tested, and phylogenetic analysis of HBV isolates has been done. The HBI prevalence was 1.9% (1 hnHBI/53) for teenage children of non-HBI mothers, compared with 16.7% (1 hnHBI/6) for those of hnHBI mothers and 2.9% (1 HBsAg-positive HBV infection [hpHBI]/34) for those of hpHBI mothers. Similar viral sequences have been found in one pair of whom both the mother and teenager have had hnHBI. In comparison with the hpHBI cases, those with hnHBI had a lower level of HBV load and a higher proportion of genotype-C strains, which were accompanied by differentiated mutations (Q129R, K141E, and Y161N) of the “a” determinant of the HBV surface gene. Our findings suggest that mother-to-teenager transmission of hnHBI can occur among those in the neonatal HBV vaccination program. PMID:23254298

Prevalence of HBsAg, knowledge, and vaccination practice against viral hepatitis B infection among doctors and nurses in a secondary health care facility in Lagos state, South-western Nigeria.

PubMed

Abiola, Abdul-Hakeem Olatunji; Agunbiade, Adebukola Bola; Badmos, Kabir Bolarinwa; Lesi, Adenike Olufunmilayo; Lawal, Abdulrazzaq Oluwagbemiga; Alli, Quadri Olatunji

2016-01-01

Hepatitis B Virus, a highly infectious blood-borne virus poses a major threat to public health globally due to its high prevalence rate and grave consequence in causing liver cirrhosis and hepatocelullar carcinoma, the third cause of cancer death worldwide. The aim is determine the prevalence of HBsAg, knowledge, and vaccination practices against viral hepatitis B infection among doctors and nurses in a health care facility. Study design was a descriptive cross-sectional study among all the doctors and nurses in the health care facility. Data was collected using pre-tested, structured, self-administered questionnaire and blood samples were taken from respondents and tested using commercial enzyme-linked immunosorbent assay (ELIZA) test kit to determine prevalence of hepatitis B surface antigen after informed consent. Ethical approval was obtained from Health Research and Ethics Committee of the Lagos University Teaching Hospital. Responses of the respondents to the knowledge and vaccination practices against viral hepatitis B infection were scored and graded as poor (<50%), fair (50-74%) and good (≥75%). The study was carried out in January, 2014. A total of 134 out of the 143 recruited respondents participated in the study. Prevalence of HBsAg was 1.5%. Among the respondents, 56.7% had good knowledge and 94.8% reported poor practice of vaccination against viral hepatitis B infection. Mean knowledge and vaccination practices scores (%) were 72.54+7.60 and 29.44+14.37 respectively. Only 29% of the respondents did post vaccination testing for anti HBsAg. Prevalence of HBsAg was low. Knowledge of viral hepatitis B was fair, and practice of post hepatitis B vaccination testing was poor. It is therefore recommended that the state ministry of health should organise further health education programme, institute compulsory occupational hepatitis B vaccination programme and post vaccination anti-HBS testing to ensure adequate antibody level in this adult population.

Single low-dose un-adjuvanted HBsAg nanoparticle vaccine elicits robust, durable immunity.

PubMed

Lugade, Amit A; Bharali, Dhruba J; Pradhan, Vandana; Elkin, Galina; Mousa, Shaker A; Thanavala, Yasmin

2013-10-01

Chitosan nanoparticles were evaluated as a vaccine delivery system for hepatitis B surface antigen (HBsAg) in the absence of adjuvant. Nano-encapsulated HBsAg (HBsAg chitosan-NP) was endocytosed more rapidly and efficiently by dendritic cells compared to soluble HBsAg. FRET analysis demonstrated that intact nanoparticles were taken up by DCs. To determine the immunogenicity of adjuvant-free nano-encapsulated HBsAg, mice were immunized with a single dose of non-encapsulated HBsAg, HBsAg chitosan-NP, or HBsAg alum. Mice immunized with adjuvant-free nanoparticle elicited anti-HBs antibodies at significantly higher titers compared to mice immunized with HBsAg alum. Elevated numbers of BAFF-R(+) B cells and CD138+ plasma cells account for the heightened anti-HBs response in nanoparticle immunized mice. Increases in Tfh cells provide a mechanism for the accumulation of anti-HBs secreting cells. Thus, chitosan nanoparticle vaccines represent a promising un-adjuvanted platform to generate robust and durable immunity to HBsAg and other subunit antigens following a single low-dose administration. In this study, chitosan nanoparticle vaccines are demonstrated as a promising un-adjuvanted platform to generate robust and durable immunity to HBsAg and other subunit antigens following a single low-dose administration in a murine model. The authors also demonstrated superior antibody response induction compared with non-encapsulated HBs antigen and HBsAg aluminum. Copyright © 2013 Elsevier Inc. All rights reserved.

Increased B and T Cell Responses in M. bovis Bacille Calmette-Guérin Vaccinated Pigs Co-Immunized with Plasmid DNA Encoding a Prototype Tuberculosis Antigen

PubMed Central

Bruffaerts, Nicolas; Pedersen, Lasse E.; Vandermeulen, Gaëlle; Préat, Véronique; Stockhofe-Zurwieden, Norbert; Huygen, Kris; Romano, Marta

2015-01-01

The only tuberculosis vaccine currently available, bacille Calmette-Guérin (BCG) is a poor inducer of CD8+ T cells, which are particularly important for the control of latent tuberculosis and protection against reactivation. As the induction of strong CD8+ T cell responses is a hallmark of DNA vaccines, a combination of BCG with plasmid DNA encoding a prototype TB antigen (Ag85A) was tested. As an alternative animal model, pigs were primed with BCG mixed with empty vector or codon-optimized pAg85A by the intradermal route and boosted with plasmid delivered by intramuscular electroporation. Control pigs received unformulated BCG. The BCG-pAg85A combination stimulated robust and sustained Ag85A specific antibody, lymphoproliferative, IL-6, IL-10 and IFN-γ responses. IgG1/IgG2 antibody isotype ratio reflected the Th1 helper type biased response. T lymphocyte responses against purified protein derivative of tuberculin (PPD) were induced in all (BCG) vaccinated animals, but responses were much stronger in BCG-pAg85A vaccinated pigs. Finally, Ag85A-specific IFN-γ producing CD8+ T cells were detected by intracellular cytokine staining and a synthetic peptide, spanning Ag85A131-150 and encompassing two regions with strong predicted SLA-1*0401/SLA-1*0801 binding affinity, was promiscuously recognized by 6/6 animals vaccinated with the BCG-pAg85A combination. Our study provides a proof of concept in a large mammalian species, for a new Th1 and CD8+ targeting tuberculosis vaccine, based on BCG-plasmid DNA co-administration. PMID:26172261

A tuberculosis vaccine based on phosphoantigens and fusion proteins induces distinct gammadelta and alphabeta T cell responses in primates.

PubMed

Cendron, Delphine; Ingoure, Sophie; Martino, Angelo; Casetti, Rita; Horand, Françoise; Romagné, François; Sicard, Hélène; Fournié, Jean-Jacques; Poccia, Fabrizio

2007-02-01

Phosphoantigens are mycobacterial non-peptide antigens that might enhance the immunogenicity of current subunit candidate vaccines for tuberculosis. However, their testing requires monkeys, the only animal models suitable for gammadelta T cell responses to mycobacteria. Thus here, the immunogenicity of 6-kDa early secretory antigenic target-mycolyl transferase complex antigen 85B (ESAT-6-Ag85B) (H-1 hybrid) fusion protein associated or not to a synthetic phosphoantigen was compared by a prime-boost regimen of two groups of eight cynomolgus. Although phosphoantigen activated immediately a strong release of systemic Th1 cytokines (IL-2, IL-6, IFN-gamma, TNF-alpha), it further anergized blood gammadelta T lymphocytes selectively. By contrast, the hybrid H-1 induced only memory alphabeta T cell responses, regardless of phosphoantigen. These latter essentially comprised cytotoxic T lymphocytes specific for Ag85B (on average + 430 cells/million PBMC) and few IFN-gamma-secreting cells (+ 40 cells/million PBMC, equally specific for ESAT-6 and for Ag85B). Hence, in macaques, a prime-boost with the H-1/phosphoantigen subunit combination induces two waves of immune responses, successively by gammadelta T and alphabeta T lymphocytes.

Efficacy of antigen dosage on the hepatitis B vaccine response in infants born to hepatitis B-uninfected and hepatitis B-infected mothers.

PubMed

Kang, Guodong; Ma, Fubao; Chen, Haiping; Yang, Yunkai; Guo, Shaohong; Wang, Zhiguo; Liang, Xiaofeng; Li, Li; Cui, Fuqiang; Zhang, Longhua

2015-08-07

To compare the safety and immunogenicity of two dosages of recombinant hepatitis B (HB) vaccine administered to infants born to HB-uninfected and HB-infected mothers. A phase III, controlled, single-blinded clinical trial was conducted with 506 healthy newborns. The newborns were assigned to three groups based on maternal levels of HB surface antigen (HBsAg) and HB e antigen (HBeAg): Group A, HBsAg negative; Group B, HBsAg positive and HBeAg negative; and Group C, HBsAg positive and HBeAg positive. Three doses of 10 or 5 μg recombinant HB vaccine were randomly administered by 1:1 within 24 h after birth, at 1 month and at 6 months. Safety data and pre- and postvaccination blood samples were collected. A total of 326, 93, and 87 subjects were included in Groups A, B, and C, respectively. Both dosages of HB vaccine were well tolerated by all subjects. The most common injection-site adverse reactions (ARs) and systemic ARs were pain and fever. After 1 month of the third dose, the Group A infants who received the 10 μg HB vaccine achieved a higher geometric mean concentration (GMC) of HB surface antibody (anti-HBs) than those who received the 5 μg dosage. Maternal anti-HBs serostatus did not influence HB vaccine immunogenicity at either dosage. In contrast, there was no significant difference in the anti-HBs seroconversion rate, GMCs, or estimated vaccine efficacy (EVE) against perinatal transmission between Groups B and C, regardless of dosage. However, the seroconversion rate and EVE of the 5 μg HB vaccine was lower in Group C than in Group B. Both dosages of the HB vaccine were well tolerated and elicited a good immune response in infants of Group A, regardless of the maternal anti-HBs serostatus. EVE did not significantly differ between Groups B and C. Clinicaltrials.gov identifier: NCT02152709. Copyright © 2015 Elsevier Ltd. All rights reserved.

Overcoming HBV immune tolerance to eliminate HBsAg-positive hepatocytes via pre-administration of GM-CSF as a novel adjuvant for a hepatitis B vaccine in HBV transgenic mice

PubMed Central

Wang, Xianzheng; Dong, Aihua; Xiao, Jingjing; Zhou, Xingjun; Mi, Haili; Xu, Hanqian; Zhang, Jiming; Wang, Bin

2016-01-01

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to be a potential vaccine adjuvant despite contradictory results from animal and human studies. The discrepancies may be due to the different doses and regimens of GM-CSF that were used, given that either mature or immature dendritic cells (DCs) could be induced under different conditions. To test the hypothesis that GM-CSF can be used as a novel adjuvant for a hepatitis B virus (HBV) therapeutic vaccine, we administered GM-CSF once per day for three days prior to vaccination with recombinant HBV vaccine (rHBVvac) in mice. We observed greater DC maturation in these pre-treated animals at day 3 as compared to day 1 or day 2 of daily GM-CSF administration. This strategy was further investigated for its ability to break the immune tolerance established in hepatitis B surface antigen-transgenic (HBsAg-Tg) animals. We found that the levels of induced anti-HBsAg antibodies were significantly higher in animals following three days of GM-CSF pre-treatment before rHBV vaccination after the third immunization. In addition to the increase in anti-HBsAg antibody levels, cell-mediated anti-HBsAg responses, including delayed-type hypersensitivity, T-cell proliferation, interferon-γ production, and cytotoxic T lymphocytes, were dramatically enhanced in the three-day GM-CSF pre-treated group. After adoptive transfers of CD8+ T cells from immunized animals, antigen-specific CD8+ T cells were observed in the livers of recipient HBsAg-Tg animals. Moreover, the three-day pre-treatments with GM-CSF prior to rHBVvac vaccination could significantly eliminate HBsAg-positive hepatocytes, suggesting beneficial therapeutic effects. Therefore, this protocol utilizing GM-CSF as an adjuvant in combination with the rHBVvac vaccine has the potential to become a novel immunotherapy for chronic hepatitis B patients. PMID:26166767

Overcoming HBV immune tolerance to eliminate HBsAg-positive hepatocytes via pre-administration of GM-CSF as a novel adjuvant for a hepatitis B vaccine in HBV transgenic mice.

PubMed

Wang, Xianzheng; Dong, Aihua; Xiao, Jingjing; Zhou, Xingjun; Mi, Haili; Xu, Hanqian; Zhang, Jiming; Wang, Bin

2016-11-01

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to be a potential vaccine adjuvant despite contradictory results from animal and human studies. The discrepancies may be due to the different doses and regimens of GM-CSF that were used, given that either mature or immature dendritic cells (DCs) could be induced under different conditions. To test the hypothesis that GM-CSF can be used as a novel adjuvant for a hepatitis B virus (HBV) therapeutic vaccine, we administered GM-CSF once per day for three days prior to vaccination with recombinant HBV vaccine (rHBVvac) in mice. We observed greater DC maturation in these pre-treated animals at day 3 as compared to day 1 or day 2 of daily GM-CSF administration. This strategy was further investigated for its ability to break the immune tolerance established in hepatitis B surface antigen-transgenic (HBsAg-Tg) animals. We found that the levels of induced anti-HBsAg antibodies were significantly higher in animals following three days of GM-CSF pre-treatment before rHBV vaccination after the third immunization. In addition to the increase in anti-HBsAg antibody levels, cell-mediated anti-HBsAg responses, including delayed-type hypersensitivity, T-cell proliferation, interferon-γ production, and cytotoxic T lymphocytes, were dramatically enhanced in the three-day GM-CSF pre-treated group. After adoptive transfers of CD8 + T cells from immunized animals, antigen-specific CD8 + T cells were observed in the livers of recipient HBsAg-Tg animals. Moreover, the three-day pre-treatments with GM-CSF prior to rHBVvac vaccination could significantly eliminate HBsAg-positive hepatocytes, suggesting beneficial therapeutic effects. Therefore, this protocol utilizing GM-CSF as an adjuvant in combination with the rHBVvac vaccine has the potential to become a novel immunotherapy for chronic hepatitis B patients.

Low-dose intradermal and intramuscular vaccination against hepatitis B.

PubMed

Bryan, J P; Sjogren, M H; Perine, P L; Legters, L J

1992-03-01

Hepatitis B and its sequelae are global problems preventable by immunization. Expense limits the use of hepatitis B vaccines, but low-dose intradermal immunization has been evaluated as a cost-saving strategy in numerous studies. With few exceptions, low-dose intradermal plasma-derived vaccines have elicited protective levels of antibody in 82%-100% of young healthy adults--a proportion similar to that noted with full-dose regimens; peak levels of antibody to hepatitis B surface antigen (HBsAg) are lower with reduced doses, however. Although children respond well to low-dose intradermal immunization, this procedure is technically difficult in neonates and should not be used for those born to HBsAg-positive mothers. For persons at high risk, antibody to HBsAg must be assessed after immunization to determine the need for a booster dose. A fourth dose 1-2 years after the initial series substantially increases antibody concentrations. In low intradermal doses, recombinant vaccine elicits lower rates of seroconversion than plasma-derived vaccine. However, low intramuscular doses of recombinant vaccine give favorable results. In short, low-dose intradermal or intramuscular immunization offers protection against hepatitis B at significant savings and may be useful for mass immunization of populations at high risk.

Immunogenicity and protective efficacy of heterologous prime-boost regimens with mycobacterial vaccines and recombinant adenovirus- and poxvirus-vectored vaccines against murine tuberculosis.

PubMed

You, Qingrui; Wu, Yongge; Wu, Yang; Wei, Wei; Wang, Changyong; Jiang, Dehua; Yu, Xianghui; Zhang, Xizhen; Wang, Yong; Tang, Zhijiao; Jiang, Chunlai; Kong, Wei

2012-11-01

To evaluate regimens using bacillus Calmette-Guérin (BCG) or recombinant BCG (rBCG) overexpressing Ag85B for priming, followed by boosting with a modified vaccinia virus Ankara strain (MVA) and/or adenovirus vector (AD) expressing an Ag85B-ESAT6 fusion protein. Cellular and humoral immune responses were determined after subcutaneous vaccination, which was employed to trigger systemic immunity against intravenous infection in a mouse model of tuberculosis (TB). Bacterial loads and lung histology were evaluated. The relative IgG2a and IgG1 antibody levels indicated that the viral-vectored vaccines generated a T-helper type 1 (Th1)-biased response after two doses of viral boost vaccinations. Boosting BCG-primed mice with viral vaccines induced a Th1 immune response that included both CD4 and CD8 T-cells generating antigen-specific interferon-gamma (IFN-γ) and CD8 T cytotoxic activity. Only mice vaccinated with two different viral boosters after BCG priming exhibited a significant reduction in bacterial burden in the lung after challenge. Histology examinations confirmed the attenuation of lung damage and more compact granulomas. After mycobacteria priming, boosting with AD85B-E6 followed by MVA85B-E6 afforded better protection than the reverse order of administration of the viral vectors. This study demonstrates the potential of multiple heterologous viral booster vaccines, although the exact correlates of protection and optimal regimens should be further investigated for the rational design of future vaccine strategies. Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Substantial decline in hepatitis B virus infections following vaccine introduction in Tajikistan.

PubMed

Khetsuriani, Nino; Tishkova, Faina; Jabirov, Shamsidin; Wannemuehler, Kathleen; Kamili, Saleem; Pirova, Zulfiya; Mosina, Liudmila; Gavrilin, Eugene; Ursu, Pavel; Drobeniuc, Jan

2015-07-31

Tajikistan, considered highly endemic area for hepatitis B virus (HBV) in a pre-vaccine era, introduced hepatitis B vaccine in 2002 and reported ≥80% coverage with three doses of hepatitis B vaccine (HepB3) since 2004. However, the impact of vaccine introduction has not been assessed. We tested residual serum specimens from a 2010 national serosurvey for vaccine-preventable diseases in Tajikistan and assessed the prevalence of HBV infection across groups defined based on the birth cohorts' routine infant hepatitis B vaccination program implementation and HepB3 coverage achieved (≥80% versus <80%). Serosurvey participants were selected through stratified multi-stage cluster sampling among residents of all regions of Tajikistan aged 1-24 years. All specimens were tested for antibodies against HBV core antigen (anti-HBc) and those found positive were tested for HBV surface antigen (HBsAg). Seroprevalence and 95% confidence intervals were calculated and compared across subgroups using Satterthwaite-adjusted chi-square tests, accounting for the survey design and sampling weights. A total of 2188 samples were tested. Prevalence of HBV infection markers was lowest among cohorts with ≥80% HepB3 coverage (ages, 1-6 years): 2.1% (95% confidence interval, 1.1-4.3%) for anti-HBc, 0.4% (0.1-1.3%) for HBsAg, followed by 7.2% (4.1-12.4%) for anti-HBc and 2.1% (0.7-6.1%) for HBsAg among cohorts with <80% HepB3 coverage (ages, 7-8 years), by 12.0% (8.7-16.3%) for anti-HBc and 3.5% (2.2-5.6%) for HBsAg among children's cohorts not targeted for vaccination (ages, 9-14 years), and 28.9% (24.5-33.8%) for anti-HBc and 6.8% (4.5-10.1%) for HBsAg among unvaccinated adult cohorts (ages, 15-24 years). Differences across groups were significant (p<0.001, chi-square) for both markers. The present study demonstrates substantial impact of hepatitis B vaccine introduction on reducing HBV infections in Tajikistan. To achieve further progress in hepatitis B control, Tajikistan should

Evaluation of vaccines in the EU TB Vaccine Cluster using a guinea pig aerosol infection model of tuberculosis.

PubMed

Williams, Ann; Hatch, Graham J; Clark, Simon O; Gooch, Karen E; Hatch, Kim A; Hall, Graham A; Huygen, Kris; Ottenhoff, Tom H M; Franken, Kees L M C; Andersen, Peter; Doherty, T Mark; Kaufmann, Stefan H E; Grode, Leander; Seiler, Peter; Martin, Carlos; Gicquel, Brigitte; Cole, Stewart T; Brodin, Priscille; Pym, Alexander S; Dalemans, Wilfried; Cohen, Joe; Lobet, Yves; Goonetilleke, Nilu; McShane, Helen; Hill, Adrian; Parish, Tanya; Smith, Debbie; Stoker, Neil G; Lowrie, Douglas B; Källenius, Gunilla; Svenson, Stefan; Pawlowski, Andrzej; Blake, Karen; Marsh, Philip D

2005-01-01

The TB Vaccine Cluster project funded by the EU Fifth Framework programme aims to provide novel vaccines against tuberculosis that are suitable for evaluation in humans. This paper describes the studies of the protective efficacy of vaccines in a guinea pig aerosol-infection model of primary tuberculosis. The objective was to conduct comparative evaluations of vaccines that had previously demonstrated efficacy in other animal models. Groups of 6 guinea pigs were immunized with vaccines provided by the relevant EU Vaccine Cluster partners. Survival over 17 or 26 weeks was used as the principal measure of vaccine efficacy following aerosol challenge with H37Rv. Counts of mycobacteria in lungs and spleens, and histopathological changes in the lungs, were also used to provide evidence of protection. A total of 24 vaccines were evaluated in 4 experiments each of a different design. A heterologous prime-boost strategy of DNA and MVA, each expressing Ag85A and a fusion protein of ESAT-6 and Ag85B in adjuvant, protected the guinea pigs to the same extent as BCG. Genetically modified BCG vaccines and boosted BCG strategies also protected guinea pigs to the same extent as BCG but not statistically significantly better. A relatively high aerosol-challenge dose and evaluation over a protracted time post-challenge allowed superior protection over BCG to be demonstrated by BCG boosted with MVA and fowl pox vectors expressing Ag85A.

Commensal Streptococcus mitis is a unique vector for oral mucosal vaccination

PubMed Central

Daifalla, Nada; Cayabyab, Mark J.; Xie, Emily; Kim, Hyeun Bum; Tzipori, Saul; Stashenko, Philip; Duncan, Margaret; Campos-Neto, Antonio

2014-01-01

The development of vaccine approaches that induce mucosal and systemic immune responses is critical for the effective prevention of several infections. Here, we report on the use of the abundant human oral commensal bacterium Streptococcus mitis as a delivery vehicle for mucosal immunization. Using homologous recombination we generated a stable rS. mitis expressing a Mycobacterium tuberculosis protein (Ag85b). Oral administration of rS. mitis in gnotobiotic piglets resulted in efficient oral colonization and production of oral and systemic anti-Ag85b specific IgA and IgG antibodies. These results support that the commensal S. mitis is potentially a useful vector for mucosal vaccination. PMID:25522856

Hepatitis B vaccination coverage and risk factors associated with incomplete vaccination of children born to hepatitis B surface antigen-positive mothers, Denmark, 2006 to 2010.

PubMed

Kunoee, Asja; Nielsen, Jens; Cowan, Susan

2016-01-01

In Denmark, universal screening of pregnant women for hepatitis B has been in place since November 2005, with the first two years as a trial period with enhanced surveillance. It is unknown what the change to universal screening without enhanced surveillance has meant for vaccination coverage among children born to hepatitis B surface antigen (HBsAg)-positive mothers and what risk factors exist for incomplete vaccination. This retrospective cohort study included 699 children of mothers positive for HBsAg. Information on vaccination and risk factors was collected from central registers. In total, 93% (651/699) of the children were vaccinated within 48 hours of birth, with considerable variation between birthplaces. Only 64% (306/475) of the children had received all four vaccinations through their general practitioner (GP) at the age of two years, and 10% (47/475) of the children had received no hepatitis B vaccinations at all. Enhanced surveillance was correlated positively with coverage of birth vaccination but not with coverage at the GP. No or few prenatal examinations were a risk factor for incomplete vaccination at the GP. Maternity wards and GPs are encouraged to revise their vaccination procedures and routines for pregnant women, mothers with chronic HBV infection and their children.

Bacterial polyester inclusions engineered to display vaccine candidate antigens for use as a novel class of safe and efficient vaccine delivery agents.

PubMed

Parlane, Natalie A; Wedlock, D Neil; Buddle, Bryce M; Rehm, Bernd H A

2009-12-01

Bioengineered bacterial polyester inclusions have the potential to be used as a vaccine delivery system. The biopolyester beads were engineered to display a fusion protein of the polyester synthase PhaC and the two key antigens involved in immune response to the infectious agent that causes tuberculosis, Mycobacterium tuberculosis, notably antigen 85A (Ag85A) and the 6-kDa early secreted antigenic target (ESAT-6) from Mycobacterium tuberculosis. Polyester beads displaying the respective fusion protein at a high density were successfully produced (henceforth called Ag85A-ESAT-6 beads) by recombinant Escherichia coli. The ability of the Ag85A-ESAT-6 beads to enhance mouse immunity to the displayed antigens was investigated. The beads were not toxic to the animals, as determined by weight gain and absence of lesions at the inoculation site in immunized animals. In vivo injection of the Ag85A-ESAT-6 beads in mice induced significant humoral and cell-mediated immune responses to both Ag85A and ESAT-6. Vaccination with Ag85A-ESAT-6 beads was efficient at stimulating immunity on their own, and this ability was enhanced by administration of the beads in an oil-in-water emulsion. In addition, vaccination with the Ag85A-ESAT-6 beads induced significantly stronger humoral and cell-mediated immune responses than vaccination with an equivalent dose of the fusion protein Ag85A-ESAT-6 alone. The immune response induced by the beads was of a mixed Th1/Th2 nature, as assessed from the induction of the cytokine gamma interferon (Th1 immune response) and increased levels of immunoglobulin G1 (Th2 immune response). Hence, engineered biopolyester beads displaying foreign antigens represent a new class of versatile, safe, and biocompatible vaccines.

Preparation and testing of a Haemophilus influenzae Type b/Hepatitis B surface antigen conjugate vaccine.

PubMed

An, So Jung; Woo, Joo Sung; Chae, Myung Hwa; Kothari, Sudeep; Carbis, Rodney

2015-03-24

The majority of conjugate vaccines focus on inducing an antibody response to the polysaccharide antigen and the carrier protein is present primarily to induce a T-cell dependent response. In this study conjugates consisting of poly(ribosylribitolphosphate) (PRP) purified from Haemophilus influenzae Type b bound to Hepatitis B virus surface antigen (HBsAg) virus like particles were prepared with the aim of inducing an antibody response to not only the PRP but also the HBsAg. A conjugate consisting of PRP bound to HBsAg via an adipic acid dihydrazide (ADH) spacer induced strong IgG antibodies to both the PRP and HBsAg. When conjugation was performed without the ADH spacer the induction of an anti-PRP response was equivalent to that seen by conjugate with the ADH spacer, however, a negligible anti-HBsAg response was induced. For comparison, PRP was conjugated to diphtheria toxoid (DT) and Vi polysaccharide purified from Salmonella Typhi conjugated to HBsAg both using an ADH spacer. The PRPAH-DT conjugate induced strong anti-PRP and anti-DT responses, the Vi-AHHBsAg conjugate induced a good anti-HBsAg response but not as strong as that induced by the PRPAH-HBsAg conjugate. This study demonstrated that in mice it was possible to induce robust antibody responses to both polysaccharide and carrier protein provided the conjugate has certain physico-chemical properties. A PRPAH-HBsAg conjugate with the capacity to induce anti-PRP and anti-HBsAg responses could be incorporated into a multivalent pediatric vaccine and simplify formulation of such a vaccine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of hepatitis B immunization on prevention of mother-to-infant transmission of hepatitis B virus and on the immune response of infants towards hepatitis B vaccine.

PubMed

Zhang, Lei; Gui, Xi-en; Teter, Caroline; Zhong, Hairong; Pang, Zhiyong; Ding, Lixiong; Li, Fengliang; Zhou, Yun; Zhang, Ling

2014-10-21

Combined immunization with hepatitis B immunoglobulin (HBIG) plus hepatitis B vaccine (HB vaccine) can effectively prevent perinatal transmission of hepatitis B virus (HBV). With the universal administration of HB vaccine, anti-HBs conferred by HB vaccine can be found increasingly in pregnant women, and maternal anti-HBs can be passed through the placenta. This study was designed to evaluate the effect of hepatitis B immunization on preventing mother-to-infant transmission of HBV and on the immune response of infants towards HB vaccine. From 2008 to 2013, a prospective study was conducted in 15 centers in China. HBsAg-positive pregnant women and their infants aged 8-12 months who completed immunoprophylaxis were enrolled in the study and tested for HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc). Antepartum administration of HBIG to HBsAg-positive women was based on individual preference. HBsAg-negative pregnant women and their infants of 7-24 months old who received HB vaccines series were enrolled and tests of their HBV markers were performed. 1202 HBsAg-positive mothers and their infants aged 8-12 months were studied and 40 infants were found to be HBsAg positive with the immunoprophylaxis failure rate of 3.3%. Infants with immunoprophylaxis failure were all born to HBeAg-positive mothers of HBV-DNA ≥6 log₁₀copies/ml. Among infants of HBeAg-positive mothers, immunoprophylaxis failure rate in vaccine plus HBIG group, 7.9% (29/367), was significantly lower than the vaccine-only group, 16.9% (11/65), p=0.021; there was no significant difference in the immunoprophylaxis failure rate whether or not antepartum HBIG was given to the pregnant woman, 10.3% (10/97) vs 9.0% (30/335), p=0.685. Anti-HBs positive rate was 56.3% (3883/6899) among HBsAg-negative pregnant women and anti-HBs positive rate was 94.2% in cord blood of anti-HBs-positive mothers. After completing the HB vaccine series, anti-HBs positive rate among infants with maternal anti

Detection of hepatitis B surface antigen in pregnant women attending a public hospital for delivery: implication for vaccination strategy in Bangladesh.

PubMed

Rumi, M A; Begum, K; Hassan, M S; Hasan, S M; Azam, M G; Hasan, K N; Shirin, M; Khan, A K

1998-08-01

Routine antenatal hepatitis B surface antigen (HBsAg) screening and immunization of risk babies is very effective in preventing perinatal transmission of hepatitis B virus (HBV). We studied 1,800 parturients attending a public hospital to assess the rationale for such vaccination in Bangladesh. In one in every 29 deliveries (63 of 1,800 or 3.5%), the mother was found to be HBsAg positive. All were asymptomatic and many (41 of 63 or 65%) without risk factors would remain undetected if HBsAg screening were performed on selected groups. Most of the HBsAg-positive mothers (54 of 63 or 85.7%) were found to be chronic carriers and 30.2% (19 of 63) were also hepatitis B e antigen (HBeAg) positive, indicating high infectivity. Although 23 cord blood were positive for HBsAg or HBeAg, none were positive for IgM antibody to hepatitis B core antigen (IgM anti-HBc), suggesting transplacental transmission of the antigens rather than intrauterine infection. These findings are discussed in relation to the cost-effectiveness of routine prenatal screening and immunization of risk babies compared with universal infant immunization.

Bacterial Artificial Chromosome Clones of Viruses Comprising the Towne Cytomegalovirus Vaccine

PubMed Central

Cui, Xiaohong; Adler, Stuart P.; Davison, Andrew J.; Smith, Larry; Habib, EL-Sayed E.; McVoy, Michael A.

2012-01-01

Bacterial artificial chromosome (BAC) clones have proven invaluable for genetic manipulation of herpesvirus genomes. BAC cloning can also be useful for capturing representative genomes that comprise a viral stock or mixture. The Towne live attenuated cytomegalovirus vaccine was developed in the 1970s by serial passage in cultured fibroblasts. Although its safety, immunogenicity, and efficacy have been evaluated in nearly a thousand human subjects, the vaccine itself has been little studied. Instead, genetic composition and in vitro growth properties have been inferred from studies of laboratory stocks that may not always accurately represent the viruses that comprise the vaccine. Here we describe the use of BAC cloning to define the genotypic and phenotypic properties of viruses from the Towne vaccine. Given the extensive safety history of the Towne vaccine, these BACs provide a logical starting point for the development of next-generation rationally engineered cytomegalovirus vaccines. PMID:22187535

Bacterial artificial chromosome clones of viruses comprising the towne cytomegalovirus vaccine.

PubMed

Cui, Xiaohong; Adler, Stuart P; Davison, Andrew J; Smith, Larry; Habib, El-Sayed E; McVoy, Michael A

2012-01-01

Bacterial artificial chromosome (BAC) clones have proven invaluable for genetic manipulation of herpesvirus genomes. BAC cloning can also be useful for capturing representative genomes that comprise a viral stock or mixture. The Towne live attenuated cytomegalovirus vaccine was developed in the 1970s by serial passage in cultured fibroblasts. Although its safety, immunogenicity, and efficacy have been evaluated in nearly a thousand human subjects, the vaccine itself has been little studied. Instead, genetic composition and in vitro growth properties have been inferred from studies of laboratory stocks that may not always accurately represent the viruses that comprise the vaccine. Here we describe the use of BAC cloning to define the genotypic and phenotypic properties of viruses from the Towne vaccine. Given the extensive safety history of the Towne vaccine, these BACs provide a logical starting point for the development of next-generation rationally engineered cytomegalovirus vaccines.

Evaluation of the Protection Provided by Hepatitis B Vaccination in India.

PubMed

Puliyel, Jacob; Naik, Pathik; Puliyel, Ashish; Agarwal, Kishore; Lal, Vandana; Kansal, Nimmi; Nandan, Devki; Tripathi, Vikas; Tyagi, Prashant; Singh, Saroj K; Srivastava, Rajeev; Sharma, Utkarsh; Sreenivas, V

2018-07-01

In India, Hepatitis B vaccination is recommended at 6 wk except for hospital-deliveries. The authors examined protection afforded by the birth dose. A case-control study was done. HBsAg and HBcAb were tested in 2671 children, 1 to 5 y and HBsAb was evaluated in a subset of 1413 children. Vaccination history was recorded. Cases were HBsAg carriers. In another analysis, children who got infected (HBsAg and/or HBcAb positive) were considered as cases. Exposed were the unvaccinated. In another analysis, exposed were those vaccinated without the birth dose. The odds ratio (OR) for HBsAg positivity with birth vaccination was 0.35 (95% CI 0.19-0.66); while with vaccination at 6 wk was 0.29 (95%CI 0.14-0.61), both compared to unvaccinated. Birth vaccination has no added protection when compared to the unvaccinated. Unvaccinated children in index study had HBsAg positivity of 4.38%. The number needed to treat (NNT) to prevent one case of HBsAg positivity was 32.6 (95% CI, 20.9 to 73.6). The odds of getting HBV infection was 0.42 (CI 0.25-0.68) with birth dose and 0.49 (CI 0.30-0.82) without the birth dose compared to the unvaccinated. Protective antibody (HBsAb) was present in about 70% of the vaccinated. In the unimmunised, in the first 2 y HBsAb protection was present in 40%. The odds ratio (OR) for HBsAb in the fully vaccinated between 4 and 5 y was 1.4 (95%CI 0.9-2.18) compared to the unvaccinated. The present study lends support to the pragmatic approach of the Government to vaccinate babies born at home starting at 6 wk.

Induction of anti-HBs in HB vaccine nonresponders in vivo by hepatitis B surface antigen-pulsed blood dendritic cells.

PubMed

Fazle Akbar, Sk Md; Furukawa, Shinya; Yoshida, Osamu; Hiasa, Yoichi; Horiike, Norio; Onji, Morikazu

2007-07-01

Antigen-pulsed dendritic cells (DCs) are now used for treatment of patients with cancers, however, the efficacy of these DCs has never been evaluated for prophylactic purposes. The aim of this study was (1) to prepare hepatitis B surface antigen (HBsAg)-pulsed human blood DCs, (2) to assess immunogenicity of HBsAg-pulsed DCs in vitro and (3) to evaluate the efficacy of HBsAg-pulsed DCs in hepatitis B (HB) vaccine nonresponders. Human peripheral blood DCs were cultured with HBsAg to prepare HBsAg-pulsed DCs. The expression of immunogenic epitopes of HBsAg on HBsAg-pulsed DCs was assessed in vitro. Finally, HBsAg-pulsed DCs were administered, intradermally to six HB vaccine nonresponders and the levels of antibody to HBsAg (anti-HBs) in the sera were assessed. HB vaccine nonresponders did not exhibit features of immediate, early or delayed adverse reactions due to administration of HBsAg-pulsed DCs. Anti-HBs were detected in the sera of all HB vaccine nonresponders within 28 days after administration of HBsAg-pulsed DCs. This study opens a new field of application of antigen-pulsed DCs for prophylactic purposes when adequate levels of protective antibody cannot be induced by traditional vaccination approaches.

Hepatitis B virus vaccination booster does not provide additional protection in adolescents: a cross-sectional school-based study.

PubMed

Chang, Yung-Chieh; Wang, Jen-Hung; Chen, Yu-Sheng; Lin, Jun-Song; Cheng, Ching-Feng; Chu, Chia-Hsiang

2014-09-23

Current consensus does not support the use of a universal booster of hepatitis B virus (HBV) vaccine because there is an anamnestic response in almost all children 15 years after universal infant HBV vaccination. We aimed to provide a booster strategy among adolescents as a result of their changes in lifestyle and sexual activity. This study comprised a series of cross-sectional serological surveys of HBV markers in four age groups between 2004 and 2012. The seropositivity rates of hepatitis B surface antigen (HBsAg) and its reciprocal antibody (anti-HBs) for each age group were collected. There were two parts to this study; age-specific HBV seroepidemiology and subgroup analysis, including effects of different vaccine types, booster response for immunogenicity at 15 years of age, and longitudinal follow-up to identify possible additional protection by HBV booster. Within the study period, data on serum anti-HBs and HBsAg in a total of 6950 students from four age groups were collected. The overall anti-HBs and HBsAg seropositivity rates were 44.3% and 1.2%, respectively. The anti-HBs seropositivity rate in the plasma-derived subgroup was significantly higher in both 15- and 18-year age groups. Overall response rate in the double-seronegative recipients at 15 years of age was 92.5% at 6 weeks following one recombinant HBV booster dose. Among the 24 recipients showing anti-HBs seroconversion at 6 weeks after booster, seven subjects (29.2%) had lost their anti-HBs seropositivity again within 3 years. Increased seropositivity rates and titers of anti-HBs did not provide additional protective effects among subjects comprehensively vaccinated against HBV in infancy. HBV booster strategy at 15 years of age was the main contributor to the unique age-related phenomenon of anti-HBs seropositivity rate and titer. No increase in HBsAg seropositivity rates within different age groups was observed. Vaccination with plasma-derived HBV vaccines in infancy provided higher

Intranasal boosting with an adenovirus-vectored vaccine markedly enhances protection by parenteral Mycobacterium bovis BCG immunization against pulmonary tuberculosis.

PubMed

Santosuosso, Michael; McCormick, Sarah; Zhang, Xizhong; Zganiacz, Anna; Xing, Zhou

2006-08-01

Parenterally administered Mycobacterium bovis BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. We examined a heterologous prime-boost regimen utilizing BCG as a prime vaccine and our recently described adenoviral vector expressing Ag85A (AdAg85A) as a boost vaccine. Since we recently demonstrated that a single intranasal but not intramuscular immunization with AdAg85A was able to induce potent protection from pulmonary Mycobacterium tuberculosis challenge in a mouse model, we compared the protective effects of parenteral and mucosal booster immunizations following subcutaneous BCG priming. Protection by BCG prime immunization was not effectively boosted by subcutaneous BCG or intramuscular AdAg85A. In contrast, protection by BCG priming was remarkably boosted by intranasal AdAg85A. Such enhanced protection by intranasal AdAg85A was correlated to the numbers of gamma interferon-positive CD4 and CD8 T cells residing in the airway lumen of the lung. Our study demonstrates that intranasal administration of AdAg85A represents an effective way to boost immune protection by parenteral BCG vaccination.

The Prevalence and Risk Factors for Hepatitis B Surface Ag Positivity in Pregnant Women in Eastern Region of Ghana

PubMed Central

Cho, Younmo; Bonsu, George; Akoto-Ampaw, Arko; Nkrumah-Mills, Grace; Nimo, Julia J.A.; Park, Jin Kyung

2012-01-01

Background/Aims The aim of this study was to evaluate the prevalence and risk factors for hepatitis B surface antigen (HBsAg) positivity in pregnant Ghanaian women. Methods We surveyed 1,500 pregnant women in Eastern region of Ghana. Direct interviews were performed by trained nurses using standardized questionnaires. Pregnant women were screened for human immunodeficiency virus (HIV) and hepatitis B infections, hemoglobin levels and sickle cell anemia as part of the antenatal check-up. Results The overall HBsAg positive rate was 10.6%, which varied among districts (13.8% for Kwahu West, 12.4% for Upper Manya, and 2.2% for Yilo Krobo). HBsAg positivity was significantly higher in women with depression (odds ratio [OR], 3.74; 95% confidence interval [CI], 2.13 to 6.57) and HIV (OR, 2.03; 95% CI, 1.06 to 3.89). Age, education, and gravidity were not related to HBsAg positivity. Anti-hepatitis B immunoglobulin for newborns of HBsAg-positive mothers is not provided at birth in public health facilities in Ghana. However, hepatitis B vaccination is provided as part of a routine vaccination schedule starting at 6 weeks of age. Conclusions To prevent mother-to-child transmission of hepatitis B, screening tests for HBsAg in pregnant women and hepatitis B vaccination of newborns immediately after birth need to be performed in this region. PMID:22570754

Booster dose vaccination for preventing hepatitis B.

PubMed

Poorolajal, Jalal; Hooshmand, Elham

2016-06-07

Antibodies against hepatitis B surface antigen (HBsAg) wane over time following hepatitis B immunisation; hence, it is unclear whether people vaccinated in three-dose or four-dose schedules of the hepatitis B vaccine are still immune when the hepatitis B surface antibody (anti-HBs) level in their body is undetectable, or lower than the level usually considered protective. This question may potentially be answered indirectly by measuring the anamnestic immune response to a booster dose of vaccine. The term 'booster' (or revaccination) refers to an additional dose of hepatitis B vaccine (HBV) given some time post-primary vaccination to induce immune memory and improve protection against hepatitis B virus (HBV) infection. To assess the benefits and harms of booster dose hepatitis B vaccination, more than five years after the primary vaccination, for preventing HBV infection in healthy individuals previously vaccinated with the hepatitis B vaccine, and with hepatitis B surface antibody (anti-HBs) levels below 10 mIU/mL. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, conference databases, and reference lists of articles to January 2016. We also contacted authors of articles. In addition, we searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials (May 2016). Randomised clinical trials addressing anamnestic immune response to a booster dose of hepatitis B vaccine, more than five years after the primary vaccination, in apparently healthy participants, vaccinated in a three-dose or four-dose schedule of the hepatitis B vaccine during the primary vaccination, without receiving an additional dose or immunoglobulin. Both review authors decided if the identified studies met the inclusion criteria or not. Primary outcomes included the proportion of participants

Evaluation of Hepatitis B Vaccination among Lichen Planus Patients.

PubMed

Balighi, K; Daneshpazhooh, M; Nasimi, M; Loloee, S; Asadi, A; Azizpour, A

2016-07-01

Lichen planus (LP) is an idiopathic chronic inflammatory mucocutaneous disease. Many reports in the literature have described hepatitis B vaccine as a predisposing factor for LP. This study was performed to determine the rate of previous vaccination against hepatitis B in LP patients. This was a cross sectional study on LP patients. Diagnosis of LP was confirmed by histological examination. Data were gathered by dermatology residents based on a checklist designed to guide their interview. Blood samples were tested for HBsAB titer, HBsAg, HCV Ab and liver function tests. One hundred & twenty four (124) patients entered the study. Females were 2.72 times more affected. The mean age of patients was 45.63 years (age range; 18-88). Forty-four (35.5%) patients had been vaccinated against hepatitis B. Lichen planus during the first six months of vaccination occurred in only one patient. Our findings bring into question the causative role of HBV vaccine in LP incidence in our population.

Adolescent booster with hepatitis B virus vaccines decreases HBV infection in high-risk adults.

PubMed

Wang, Yuting; Chen, Taoyang; Lu, Ling-Ling; Wang, Minjie; Wang, Dongmei; Yao, Hongyu; Fan, Chunsun; Qi, Jun; Zhang, Yawei; Qu, Chunfeng

2017-02-15

Neutralizing antibodies (anti-HBs) after immunization with hepatitis B virus (HBV) vaccines against HBV surface antigen (HBsAg) wane after 10-15years. We analyzed the effect of an adolescent booster given to vaccination-protected children born to mothers with different HBsAg-carrying status against HBV infection in their mature adulthood. A total of 9793 individuals, who were HBsAg-negative at childhood (baseline) and donated blood samples, both during childhood and adulthood, from the vaccination group in "Qidong Hepatitis B Intervention Study", were enrolled. Among them 7414 received a one-dose, 10μg-recombinant HBV vaccine booster at 10-14years of age. At endpoint (23-28years of age), we determined the HBV serological markers and quantified their serum HBV-DNA in each of the chronic HBV-infected adults. Fifty-seven adults were identified as chronic HBV infection, indicated by HBsAg(+)&anti-HBc(+) for more than 6months. The individuals who were born to HBsAg-positive mothers (high-risk adults) had significantly increased risk of developing chronic HBV infections in adulthood compared with those who were born to HBsAg-negative mothers; the adjusted odds ratio (OR) was 12.56, 95%CI:7.14-22.08. The seronegative status of anti-HBs at 10-11years of age significantly increased the risk of HBV infections among the high-risk adults. When HBsAg(-)&anti-HBc(+) children who were born to HBsAg-positive mothers 70% of them remained as the status and 10% of them developed HBsAg(+)&anti-HBc(+). While when they were born to HBsAg-negative mothers 1.05% HBsAg(-)&anti-HBc(+) children developed HBsAg(+)&anti-HBc(+) and 24.74% of them remained as the status in 12-18years. One dose of adolescent booster showed significant protection on high-risk adults from chronic HBV infection; P for trend was 0.015. Maternal HBsAg-positive status was an independent risk factor for vaccination-protected children to develop HBV breakthrough infection in adulthood. Adolescent boosters might be

Substantial variation in the hepatitis B surface antigen (HBsAg) in hepatitis B virus (HBV)-positive patients from South Africa: Reliable detection of HBV by the Elecsys HBsAg II assay.

PubMed

Gencay, Mikael; Vermeulen, Marion; Neofytos, Dionysis; Westergaard, Gaston; Pabinger, Stephan; Kriegner, Albert; Seffner, Anja; Gohl, Peter; Huebner, Kirsten; Nauck, Markus; Kaminski, Wolfgang E

2018-04-01

It is essential that hepatitis B surface antigen (HBsAg) diagnostic assays reliably detect genetic diversity in the major hydrophilic region (MHR) of HBsAg to avoid false-negative results. Mutations in this domain display marked ethno-geographic variation and may lead to failure to diagnose hepatitis B virus (HBV) infection. Evaluate diagnostic performance of the Elecsys ® HBsAg II Qualitative assay in a cohort of South African HBV-positive blood donors. A total of 179 South African HBsAg- and HBV DNA > 100 IU/mL-positive blood donor samples were included. Samples were sequenced for genetic variation in HBsAg MHR using next-generation ultra-deep sequencing. HBsAg seropositivity was determined using the Roche Elecsys HBsAg II Qualitative assay. Mutation rates were compared between the first (amino acids 124-137) and second (amino acids 139-147) loops of the immunodominant MHR 'a' determinant region. Frequency of occult HBV infection-associated Y100C mutations was also determined. We observed a total of 279 MHR mutations (117 variants) in 102 (57%) samples, of which 91 were located in the 'a' determinant region. The major vaccine-induced escape mutation G145R was observed in two samples. All occult HBV infection-associated Y100C and common diagnostic and vaccine-escape-associated P120T, G145R, K122R, M133L, M133T, Q129H, G130N, and T126S mutations were reliably detected by the assay, which consistently detected the presence of HBsAg in all 179 samples including samples with 11 novel mutations. Despite substantial variation in HBsAg MHR, the Elecsys HBsAg II Qualitative assay robustly detects HBV infection in this South African cohort. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Partial reconstitution of the CD4+-T-cell compartment in CD4 gene knockout mice restores responses to tuberculosis DNA vaccines.

PubMed

D'Souza, Sushila; Romano, Marta; Korf, Johanna; Wang, Xiao-Ming; Adnet, Pierre-Yves; Huygen, Kris

2006-05-01

Reactivation tuberculosis (TB) is a serious problem in immunocompromised individuals, especially those with human immunodeficiency virus (HIV) coinfection. The adaptive immune response mediated by CD4+ and CD8+ T cells is known to confer protection against TB. Hence, vaccines against TB are designed to activate these two components of the immune system. Anti-TB DNA vaccines encoding the immunodominant proteins Ag85A, Ag85B, and PstS-3 from Mycobacterium tuberculosis are ineffective in mice lacking CD4+ T cells (CD4-/- mice). In this study, we demonstrate that reconstitution of the T-cell compartment in CD4-/- mice restores vaccine-specific antibody and gamma interferon (IFN-gamma) responses to these DNA vaccines. The magnitude of the immune responses correlated with the extent of reconstitution of the CD4+-T-cell compartment. Reconstituted mice vaccinated with DNA encoding PstS-3, known to encode a dominant D(b)-restricted CD8+-T-cell epitope, displayed CD8+-T-cell responses not observed in CD4-/- mice. M. tuberculosis challenge in reconstituted mice led to the extravasation of IFN-gamma-producing CD4+ and CD8+ T cells into lungs, the primary site of bacterial replication. Importantly, a reconstitution of 12 to 15% of the CD4+-T-cell compartment resulted in Ag85B plasmid DNA-mediated protection against a challenge M. tuberculosis infection. Our findings provide evidence that anti-TB DNA vaccines could be effective in immunodeficient individuals after CD4+-T-lymphocyte reconstitution, as may occur following antiretroviral therapy in HIV+ patients.

Universal immunization of infants with low doses of a low-cost, plasma-derived hepatitis B vaccine in South Africa.

PubMed Central

Schoub, B. D.; Matai, U.; Singh, B.; Blackburn, N. K.; Levin, J. B.

2002-01-01

OBJECTIVE: To evaluate the effectiveness of universal vaccination against viral hepatitis B in South Africa among 18-month-old rural children. METHODS: Children were immunized with a course of low-dose (1.5 microg), plasma-derived hepatitis B vaccine at 6, 10 and 14 weeks of age, and blood samples from the children were tested for three hepatitis B markers: hepatitis B surface antigen (HBsAg), anti-HBs and anti-HBc. FINDINGS: One year after vaccination, a protective anti-HBs antibody titre of at least 10 IU/l was present in 669/769 (87.0%) of blood serum samples tested. Only 3/756 children (0.4%) were HBsAg positive and a fourth child was anti-HBc positive (HBsAg negative). This is a marked decrease compared to the hepatitis B prevalences reported in previous studies. Among rural migrant mine-workers, for example, HBsAg prevalence was 9.9%, and was 10.1% among children 0-6 years of age in the Eastern Cape Province. CONCLUSION: The low-dose, plasma-derived hepatitis B vaccine, which is affordable to most developing countries, was very successful in controlling endemic hepatitis B infection, where the virus is predominantly spread by horizontal transmission among infants and young children. PMID:12075363

Acute hepatitis B caused by a vaccine-escape HBV strain in vaccinated subject: sequence analysis and therapeutic strategy.

PubMed

Luongo, Monica; Critelli, Rosina; Grottola, Antonella; Gitto, Stefano; Bernabucci, Veronica; Bevini, Mirco; Vecchi, Chiara; Montagnani, Giuliano; Villa, Erica

2015-01-01

HBV vaccine contains the 'a' determinant region, the major immune-target of antibodies (anti-HBs). Failure of immunization may be caused by vaccine-induced or spontaneous 'a' determinant surface gene mutants. Here, we evaluate the possible lack of protection by HBV vaccine, describing the case of an acute hepatitis B diagnosed in a 55-year-old Caucasian male unpaid blood donor, vaccinated against HBV. Sequencing data for preS-S region revealed multiple point mutations. Of all the substitutions found, Q129H, located in the "a" determinant region of HBsAg, can alter antigenicity, leading to mutants. This mutant may cause vaccine failure especially when associated with high viremia of infecting source. Copyright © 2014 Elsevier B.V. All rights reserved.

Optimization and scale-up of cell culture and purification processes for production of an adenovirus-vectored tuberculosis vaccine candidate.

PubMed

Shen, Chun Fang; Jacob, Danielle; Zhu, Tao; Bernier, Alice; Shao, Zhongqi; Yu, Xuefeng; Patel, Mehul; Lanthier, Stephane; Kamen, Amine

2016-06-17

Tuberculosis (TB) is the second leading cause of death by infectious disease worldwide. The only available TB vaccine is the Bacille Calmette-Guerin (BCG). However, parenterally administered Mycobacterium bovis BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. AdAg85A, an adenoviral vector expressing the mycobacterial protein Ag85A, is a new tuberculosis vaccine candidate, and has shown promising results in pre-clinical studies and phase I trial. This adenovirus vectored vaccine is produced using HEK 293 cell culture. Here we report on the optimization of cell culture conditions, scale-up of production and purification of the AdAg85A at different scales. Four commercial serum-free media were evaluated under various conditions for supporting the growth of HEK293 cell and production of AdAg85A. A culturing strategy was employed to take advantages of two culture media with respective strengths in supporting the cell growth and virus production, which enabled to maintain virus productivity at higher cell densities and resulted in more than two folds of increases in culture titer. The production of AdAg85A was successfully scaled up and validated at 60L bioreactor under the optimal conditions. The AdAg85A generated from the 3L and 60L bioreactor runs was purified through several purification steps. More than 98% of total cellular proteins was removed, over 60% of viral particles was recovered after the purification process, and purity of AdAg85A was similar to that of the ATCC VR-1516 Ad5 standard. Vaccination of mice with the purified AdAg85A demonstrated a very good level of Ag85A-specific antibody responses. The optimized production and purification conditions were transferred to a GMP facility for manufacturing of AdAg85A for generation of clinical grade material to support clinical trials. Crown Copyright © 2016. Published by Elsevier Ltd. All rights

Occult Hepatitis B Virus Infection in a Previously Vaccinated Injection Drug User.

PubMed

Powell, Eleanor A; Razeghi, Sanam; Zucker, Stephen; Blackard, Jason T

2016-02-01

Occult hepatitis B virus (HBV) is defined by the presence of HBV DNA in patient sera in the absence of HBsAg. Occult HBV has been associated with hepatocellular carcinoma, reactivation during immune suppression, and transmission to others. While the hepatitis B vaccine is very effective at preventing chronic HBV infection, recent studies indicate it is less effective at preventing occult HBV following infant vaccination. No studies, however, have examined the efficacy of adult HBV vaccination at preventing occult HBV. Here, we present the first report of occult HBV following adult vaccination. A 21-year old Caucasian female presented with tricuspid valve endocarditis secondary to methicillin-susceptible Staphylococcus aureus with non-ischemic cardiomyopathy. She reported active use of intravenous drugs. Her liver enzymes were elevated (ALT = 1873 IU/mL; AST = 4518 IU/mL), and she was found to have HCV and occult HBV. HBV viral loads ranged from 4608 - 8364 copies IU/mL during hospitalization. The patient's HBV was sequenced and found to be genotype D3 without any known diagnostic escape mutations. Immune complexes that may have prevented HBsAg detection were not observed. HBV vaccination in infancy is effective at preventing chronic HBV infection but is less effective at preventing occult HBV infection. Similar studies examining the efficacy of adult HBV vaccination in preventing occult HBV have not been performed. This case highlights the importance of carefully determining the HBV status of high-risk individuals, as vaccination history and the presence of anti-HBs may not be adequate to rule out HBV infection, even in the absence of HBsAg.

An inducible expression system for high-level expression of recombinant proteins in slow growing mycobacteria.

PubMed

Leotta, Lisa; Spratt, Joanne M; Kong, Carlyn U; Triccas, James A

2015-09-01

A novel protein expression vector utilising the inducible hspX promoter of Mycobacterium tuberculosis was constructed and evaluated in this study. High-level induction of three mycobacterial antigens, comprising up to 9% of bacterial sonicate, was demonstrated in recombinant Mycobacterium bovis BCG when grown under low-oxygen tension, which serves to enhance hspX promoter activity. Recombinant proteins were efficiently purified from bacterial lysates in a soluble form by virtue of a C-terminal 6-histidine tag. Purification of the immunodominant M. tuberculosis Ag85B antigen using this system resulted in a recombinant protein that stimulated significant IFN-γ release from Ag85B-reactive T cells generated after vaccination of mice with an Ag85B-expressing vaccine. Further, the M. tuberculosis L-alanine dehydrogenase (Ald) protein purified from recombinant BCG displayed strong enzymatic activity in recombinant form. This study demonstrated that high levels of native-like recombinant mycobacterial proteins can be produced in mycobacterial hosts, and this may aid the analysis of mycobacterial protein function and the development of new treatments. Copyright © 2015 Elsevier B.V. All rights reserved.

[Influenza vaccine in 85-and-over aged: motivation of elderly and family physicians to vaccinate or not].

PubMed

van Haaren, K M; van den Brande, K J; Dekker, F W; Ligthart, G J; Springer, M P

1995-10-21

To determine on what grounds persons over 85 years are or are not vaccinated against influenza. Descriptive. Gerontological Research Centre and Department of General Practice Medicine, University of Leiden, the Netherlands. A random sample (n = 331) of the general population of Leiden aged 85 years or older and not institutionalized were interviewed. Early in October 1993, 163 interviews were suitable for analysis (response rate 54%). An analysis of non-responders revealed no significant difference as regards gender and housing, but persons aged 90 and older were under-represented. The general practitioners (n = 41) of the 163 elderly persons were interviewed about these persons (response: n = 127; 78%) and about influenza vaccination in general (response: n = 33; 82%). The vaccination coverage rates were 51% according to the elderly and 56% according to the GPs; those of elderly people with an indication (48% according to themselves and 64% according to the GP) 52% and 67%, respectively. Reasons for elderly people not to accept vaccination were that they considered vaccination unnecessary, that they felt well and wanted to avoid possible adverse effects. A doctor's recommendation to have vaccination done was a positive influence. GPs' motives not to vaccinate were absence of an indication and the elderly person's wish. Only two-thirds of those over 85 not living in a nursing home with an indication for influenza vaccination were indeed vaccinated. Information about the possible damage done by influenza and about the pros and cons of vaccination, together with a doctor's advice to be vaccinated appeared to have a positive effect on the vaccination coverage.

Responses to hepatitis B vaccine in isolated anti-HBc positive adults

PubMed Central

Yao, Jun; Ren, Wen; Chen, Yongdi; Jiang, Zhenggang; Shen, Lingzhi; Shan, Huan; Dai, Xuewei; Li, Jing; Liu, Ying; Qiu, Yan; Ren, Jingjing

2016-01-01

ABSTRACT Immune responses of isolated anti-HBc subjects are not well characterized in populations in China. This study aimed to evaluate immune responses to hepatitis B vaccination in isolated anti-HBc positive subjects. A cohort of 608 subjects were selected and separated into isolated anti-HBc (negative for HBsAg and anti-HBs, positive for anti-HBc) and control (negative for HBsAg, anti-HBs, and anti-HBc) groups, who were matched by age and sex. All subjects received 3 doses of hepatitis B vaccine (20μg) at months 0, 1, and 3, followed by testing for serological responses 1 month after the third vaccination. The positive seroprotection rate and geometric mean titer (GMT) for hepatitis B surface antibody (anti-HBs) of isolated anti-HBc subjects were significantly lower than those in the control group(86.2% vs.92.1%, P = 0.02; 47.26 vs.97.81 mIU/mL, P < 0.001). When stratified by age, positive seroprotection rate in the isolated anti-HBc group were 92%, 88.5% and 79.4% in the 20–34, 35–49, and 50–60 y old subgroups, respectively (χ2 = 5.919, P = 0.04). Additionally, the GMT level for anti-HBs in the isolated anti-HBc group for different age subgroups were 104.43, 47.87 and 31.79 mIU/mL respectively (χ2 = 19.44, P < 0.001). The GMT level for anti-HBc before vaccination were negatively correlated with GMT for anti-HBs after 3 doses of hepatitis B vaccine (r = −0.165, P < 0.001). In conclusion, isolated anti-HBc positive subjects can achieve good immune responses after hepatitis B vaccination, and the positive seroprotection rate and GMT level for anti-HBs were lower than the control group. Better responses could be observed in young adults, and significant negative correlations were found between GMT of anti-HBc before vaccination and GMT of anti-HBs after vaccination. PMID:27065099

Responses to hepatitis B vaccine in isolated anti-HBc positive adults.

PubMed

Yao, Jun; Ren, Wen; Chen, Yongdi; Jiang, Zhenggang; Shen, Lingzhi; Shan, Huan; Dai, Xuewei; Li, Jing; Liu, Ying; Qiu, Yan; Ren, Jingjing

2016-07-02

Immune responses of isolated anti-HBc subjects are not well characterized in populations in China. This study aimed to evaluate immune responses to hepatitis B vaccination in isolated anti-HBc positive subjects. A cohort of 608 subjects were selected and separated into isolated anti-HBc (negative for HBsAg and anti-HBs, positive for anti-HBc) and control (negative for HBsAg, anti-HBs, and anti-HBc) groups, who were matched by age and sex. All subjects received 3 doses of hepatitis B vaccine (20μg) at months 0, 1, and 3, followed by testing for serological responses 1 month after the third vaccination. The positive seroprotection rate and geometric mean titer (GMT) for hepatitis B surface antibody (anti-HBs) of isolated anti-HBc subjects were significantly lower than those in the control group(86.2% vs.92.1%, P = 0.02; 47.26 vs.97.81 mIU/mL, P < 0.001). When stratified by age, positive seroprotection rate in the isolated anti-HBc group were 92%, 88.5% and 79.4% in the 20-34, 35-49, and 50-60 y old subgroups, respectively (χ2 = 5.919, P = 0.04). Additionally, the GMT level for anti-HBs in the isolated anti-HBc group for different age subgroups were 104.43, 47.87 and 31.79 mIU/mL respectively (χ2 = 19.44, P < 0.001). The GMT level for anti-HBc before vaccination were negatively correlated with GMT for anti-HBs after 3 doses of hepatitis B vaccine (r = -0.165, P < 0.001). In conclusion, isolated anti-HBc positive subjects can achieve good immune responses after hepatitis B vaccination, and the positive seroprotection rate and GMT level for anti-HBs were lower than the control group. Better responses could be observed in young adults, and significant negative correlations were found between GMT of anti-HBc before vaccination and GMT of anti-HBs after vaccination.

Effect of hepatitis B vaccination in hepatitis B surface antibody-negative pregnant mothers on the vertical transmission of hepatitis B virus from father to infant.

PubMed

Cao, Li-Hua; Li, Yun-Ru; Wang, Shou-Yun; Liu, Zhi-Min; Sun, Shao-Chun; Xu, Dong-Bo; Zhang, Ji-Dong

2015-07-01

The aim of the present study was to investigate the effects of vaccination with the hepatitis B vaccine (HBVac) in HB surface antibody (HBsAb)-negative pregnant mothers on the vertical transmission of HB virus (HBV) from father to infant. All the fathers tested positive for the serum HBV DNA and HB surface antigen (HBsAg) markers. The pregnant females were divided into an observation group or a control group depending on whether their serum was HBsAb-negative or positive. A total of 93 healthy individuals without HBV infection were included in a blank group, while 96 females who were serum HBV marker-negative or HB core antibody (HBcAb)-positive/(HBsAb)-negative were included in the observation group. The control group comprised 89 females who all tested positive for serum HBsAb, HB envelope antibodies and HBcAb. In the observation group, the positive rate of HBV DNA in the newborns was 7.29% (7/96), the positive rate of HBsAg was 3.13% (3/96) and the positive rate of HBsAb was 81.3% (78/96). In the control group, the positive rates of HBV DNA, HBsAg and HBsAb in the newborns were 4.49% (4/89), 2.25% (2/89) and 89.9% (80/89), respectively. No statistically significant differences were observed between the two groups. Therefore, the results of the present study indicate that HBVac treatment for HBsAb-negative pregnant females may have a positive role in blocking the vertical transmission of HBV from father to infant, as long as the vaccination is able to induce the production of a sufficient quantity of HBsAb. The HBVac exhibited no difference compared with pre-pregnancy HBsAb in blocking the vertical transmission of HBV from father to infant.

HBsAg level and hepatitis B viral load correlation with focus on pregnancy

PubMed Central

Belopolskaya, Maria; Avrutin, Viktor; Firsov, Sergey; Yakovlev, Alexey

2015-01-01

Background Viral load measurement is necessary to estimate mother-to-child transmission risk for women with chronic hepatitis B (CHB), however, it is expensive. The present study aimed to investigate the relationship between HBsAg and hepatitis B virus (HBV) DNA levels, and to determine potential applications of HBsAg level monitoring for estimating viral load. Methods 85 patients with CHB (31 pregnant women, 26 non-pregnant women, 28 men) were included in the study. HBV DNA level was measured by real-time PCR, and HBsAg level by chemiluminescent immunoassay method. Dependency between viral load and HBsAg level was determined by Spearman correlation coefficient ρ. Results The correlation between HBsAg and HBV DNA levels was significant for all patients [ρ=0.3762 (P<0.0005; n=85)]. In the group of pregnant women, a low (unmeasurable) HBV DNA level led to a decrease in the Spearman coefficient ρ. In almost all cases a low level of the HBsAg corresponded to a low HBV DNA level. Only 2 patients had a low level of HBsAg and a relatively high viral load. By contrast, a high HBsAg level was observed in patients both with high and low viral load. Conclusions Correlation between HBsAg and HBV DNA levels is significant. In most cases, a low level of HBsAg indicates a low HBV DNA level, whereas a high HBsAg level does not always correspond to a high viral load. The measurement of HBV DNA level is necessary for pregnant women with a high HBsAg level. PMID:26127004

AG 85, a major secretion protein of Mycobacterium tuberculosis, can be identified in ancient bone.

PubMed

Schmidt-Schultz, Tyede H; Schultz, Michael

2015-06-01

For the confirmation of Ag 85 in ancient and recent ECM of native macerated human bone, five cases were investigated. In three individuals, highly positive results for Ag 85 were identified in Western blot: 1) a male from Arzhan, South Siberia, dating from the 7th century BC, 2) a male from Kirchberg in Hesse, Germany, dating from the 10th - 12th century AD and 3) a recent female with a proven diagnosis of TB. As a negative control, a recent male is presented who did not suffer from TB. In another recent male, Ag 85 could be identified only very weakly. From cases in the literature it is well-known that highly positive results for Ag 85 indicate active TB, however, weakly positive results indicate a silent initial infection with Mtb. Thus, apparently, also in ancient individuals, it might well be possible to differentiate between diseased persons and disease carriers using paleoproteomic techniques. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Current seroprevalence, vaccination and predictive value of liver enzymes for hepatitis B among refugees in Germany].

PubMed

Hampel, Annika; Solbach, Philipp; Cornberg, Markus; Schmidt, Reinhold E; Behrens, Georg M N; Jablonka, Alexandra

2016-05-01

Currently only vague estimates exist for the seroprevalence and vaccination status for viral hepatitis B (HBV) in refugees arriving in Germany during the current refugee crisis. To assess the prevalence of hepatitis B in refugees arriving in northern Germany in 2015. In a cross-sectional study in 793 patients from all age groups tests for serological markers of hepatitis B virus infection (HBsAg, anti-HBc) and liver enzymes (ALT, AST, bilirubin, γGT, alkaline phosphatase) were performed in August 2015 at six reception centers in northern Germany. In 258 patients anti-HBs antibodies were assessed additionally. Of the tested refugees, 76.7 % were male, the median age was 28.8 ± 11.4 years, and 7.8 % were children under the age of 18. The overall prevalence of HBsAg and total anti-HBc was 2.3 % and 14.0 % respectively (2.5 % and 14.5 % in men; 1.2 % and 13.5 % in women). Prevalence was highest in 35 to 49-year-old patients for HBsAg (3.1 %) and for refugees over 50 years for anti-HBc (38 %). No immunity to Hepatitis B was found in 62 %, 18.6 % had been vaccinated against Hepatitis B, while 50 % of children aged up to 15 years (n = 12) had been vaccinated. Positive predictive values of elevated AST and ALT for detection of HBsAg was 0 and 0.016, respectively. Only two patients with a positive HBsAg had elevated transaminases. This study showed a high prevalence of HBsAg in a German refugee sample in comparison to the general German population. Liver enzymes are not an appropriate tool for screening for hepatitis B virus infection.

Structural characterization by NMR of a double phosphorylated chimeric peptide vaccine for treatment of Alzheimer's disease.

PubMed

Ramírez-Gualito, Karla; Richter, Monique; Matzapetakis, Manolis; Singer, David; Berger, Stefan

2013-04-26

Rational design of peptide vaccines becomes important for the treatment of some diseases such as Alzheimer's disease (AD) and related disorders. In this study, as part of a larger effort to explore correlations of structure and activity, we attempt to characterize the doubly phosphorylated chimeric peptide vaccine targeting a hyperphosphorylated epitope of the Tau protein. The 28-mer linear chimeric peptide consists of the double phosphorylated B cell epitope Tau₂₂₉₋₂₃₇[pThr231/pSer235] and the immunomodulatory T cell epitope Ag85B₂₄₁₋₂₅₅ originating from the well-known antigen Ag85B of the Mycobacterium tuberculosis, linked by a four amino acid sequence -GPSL-. NMR chemical shift analysis of our construct demonstrated that the synthesized peptide is essentially unfolded with a tendency to form a β-turn due to the linker. In conclusion, the -GPSL- unit presumably connects the two parts of the vaccine without transferring any structural information from one part to the other. Therefore, the double phosphorylated epitope of the Tau peptide is flexible and accessible.

Efficacy of combined hepatitis B immunoglobulin and hepatitis B vaccine in blocking father-infant transmission of hepatitis B viral infection.

PubMed

Cao, L-H; Liu, Z-M; Zhao, P-L; Sun, S-C; Xu, D-B; Shao, M-H; Zhang, J-D

2015-05-04

The aim of this study was to examine the efficacy of combined immunization of hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine (HBVac) in blocking father-infant transmission of hepatitis B virus (HBV). Newborns positive at birth for blood HBV sur-face antigen (HBsAg) and/or HBV DNA were selected and immunized with HBIG combination HBVac. At 7 months, HBV markers and HBV DNA of each neonate were measured using electrochemiluminescence with the Cobas-e-411 Automatic Electrochemiluminescence Immuno-assay Analyzer and fluorescence quantitative polymerase chain reaction. Among all 7-month-old subjects, the negative conversion rates of HBV DNA and HBsAg were 48/61 (78.7%) and 19/41 (46.3%), respectively. Therefore, this study demonstrated that prompt combination injection of HBIG and HBVac can protect some of the HBV DNA- and/ or HBsAg-positive newborns from HBV.

Early childhood transmission of hepatitis B prior to the first hepatitis B vaccine dose is rare among babies born to HIV-infected and non-HIV infected mothers in Gulu, Uganda

PubMed Central

Van Geertruyden, J.P.; Ssenyonga, R.; Opio, C.K.; Kaducu, J.M.; Sempa, J.B.; Colebunders, R.; Ocama, P.

2017-01-01

Background Hepatitis B (HBV) in sub-Saharan Africa is believed to be horizontally acquired. However, because of the high HBV prevalence in northern Uganda, no hepatitis B vaccination at birth and no access to HBV immunoglobulin, we hypothesize that vertical transmission also could also play an important role. We therefore investigated the incidence of HBV among babies presenting for their first HBV vaccine dose in Gulu, Uganda. Methods We recruited mothers and their babies (at least 6-week old) presenting for their postnatal care and first HBV vaccine dose respectively. Socio-demographic and risk factors for HBV transmission were recorded. Mothers were tested for Hepatitis B core antibody (anti-HBc-IgG) and hepatitis B surface antigen (HBsAg). HBsAg-positive sera were tested for hepatitis B e antigen (HBeAg) and HBV viral load (HBVDNA). Babies were tested for HBsAg at presentation and at the last immunization visit. A sample of HBsAg-negative babies were tested for HBVDNA. Incident HBV infection was defined by either a positive HBsAg or HBVDNA test. Chi-square or fisher's exact tests were utilized to investigate associations and t-tests or Wilcoxon rank-sum test for continuous differences. Results We recruited 612 mothers, median age 23 years (IQR 20–28). 53 (8.7%) were HBsAg-positive and 339 (61.5%) were anti-HBc-IgG-positive. Ten (18.9%) of the HBsAg-positive mothers were HBeAg-positive. Median HBVDNA levels of HBV-infected mothers was 5.7log (IQR 4.6–7.0) IU/mL with 9 (17.6%) having levels ≥105 IU/mL. Eighty (13.3%) mothers were HIV-infected of whom 9 (11.5%) were co-infected with HBV. No baby tested HBsAg or HBVDNA positive. Conclusion Vertical transmission does not seem to contribute substantially to the high HBV endemicity in northern Uganda. The current practice of administering the first HBV vaccine to babies in Uganda at six weeks of age may be adequate in control of HBV transmission. PMID:28434689

Immunostimulatory activities of dendritic cells loaded with adenovirus vector carrying HBcAg/HBsAg

PubMed Central

Jia, Hongyu; Li, Chunling; Zhang, Yimin; Yu, Liang; Xiang, Dairong; Liu, Jun; Chen, Fengzhe; Han, Xiaochun

2015-01-01

Objective: This study is to investigate the immunostimulatory activities of dendritic cells (DCs) transfected with HBcAg and/or HBsAg recombinant adenovirus (rAd). Methods: DCs were transfected with rAd (DC/Ad-C+Ad-S, DC/Ad-C, and DC/Ad-S), or pulsed with HBcAg antigen (DC/HBcAg). Flow cytometry was used to detect the phenotype of DCs and the cytokine production of T lymphocytes. Mice were vaccinated with DCs transfected with rAd or pulsed with antigen, and DNA vaccine. Mixed lymphocyte reaction (MLR) was used to evaluate the T-cell stimulatory capacity, and HBcAg-specific cytotoxic T lymphocyte (CTL) activity was assessed. Results: Phenotypic analysis showed that DCs transfected with rAd or pulsed with HBcAg antigen exhibited mature phenotypes. MLR indicated no significant differences in stimulating T-cell proliferation between the DC/rAd and DC/HBcAg groups. When mixed with DCs, Th and Tc cells mainly secreted IFN-γ, indicating type I immune responses. In vaccinated mice, DCs transduced with rAd and pulsed with HBcAg induced significantly more IFN-γ secretion from Th cells, compared with DNA vaccine, indicating stronger Th1 response. Moreover, DCs transduced with rAd stimulated Tc cells to produce more IFN-γ, indicating stronger Tc1 response. In vaccinated mice, HBcAg-specific CTL activities were decreased in the following order: the DC/Ad-C+Ad-S, DC/Ad-C, DC/Ad-S, DC/HBcAg, and DNA vaccine groups. Conclusion: DCs transfected with rAd induce stronger Th1/Tc1 (type I) cell immune responses and specific CTL response than HBcAg-pulsed DCs or DNA vaccine. Our findings suggest that DCs transfected with rAd-C/rAd-S might provide an effective approach in the treatment of persistent hepatitis B virus infection. PMID:26064236

Compare the Difference of B-cell Epitopes of EgAgB1 and EgAgB3 Proteins Selected through Bioinformatic Analysis

NASA Astrophysics Data System (ADS)

An, Mengting; Zhang, Fengbo; Zhu, Yuejie; Zhao, Xiao; Ding, Jianbing

2018-01-01

Cystic echinococcosis, as a zoonosis, seriously endangers humans and animals, so early diagnosis of this disease is particularly important. Therefore, this study is to predict B-cell epitopes of EgAgB1 and EgAgB3 proteins by bioinformatics software. B-cell epitopes of EgAgB1 and EgAgB3 proteins are predicted using DNAStar and IEDB software. The results suggest that there are two potential B-cell epitopes in EgAgB1, which located in the 8-15 and 31-37 amino acid residue segments. And two potential B-cell epitopes in EgAgB2, located in the 20∼27 and 47∼53 amino acid residue segments. This study predicted the B-cell epitopes of EgAgB1 and EgAgB3 proteins, which laid the foundation for the early diagnosis of Cystic echinococcosis.

Efficacy of Neonatal HBV Vaccination on Liver Cancer and Other Liver Diseases over 30-Year Follow-up of the Qidong Hepatitis B Intervention Study: A Cluster Randomized Controlled Trial

PubMed Central

Fan, Chunsun; Zhan, Qimin; Wang, Yuting; Lu, Jianhua; Lu, Ling-ling; Ni, Zhengping; Huang, Fei; Yao, Hongyu; Zhu, Jian; Fan, Jian; Zhu, Yuanrong; Wu, Zhiyuan; Liu, Guoting; Gao, Wenhong; Zang, Mengya; Wang, Dongmei; Dai, Min; Hsia, Chu Chieh; Zhang, Yawei; Sun, Zongtang

2014-01-01

Background Neonatal hepatitis B vaccination has been implemented worldwide to prevent hepatitis B virus (HBV) infections. Its long-term protective efficacy on primary liver cancer (PLC) and other liver diseases has not been fully examined. Methods and Findings The Qidong Hepatitis B Intervention Study, a population-based, cluster randomized, controlled trial between 1985 and 1990 in Qidong, China, included 39,292 newborns who were randomly assigned to the vaccination group in which 38,366 participants completed the HBV vaccination series and 34,441 newborns who were randomly assigned to the control group in which the participants received neither a vaccine nor a placebo. However, 23,368 (67.8%) participants in the control group received catch-up vaccination at age 10–14 years. By December 2013, a total of 3,895 (10.2%) in the vaccination group and 3,898 (11.3%) in the control group were lost to follow-up. Information on PLC incidence and liver disease mortality were collected through linkage of all remaining cohort members to a well-established population-based tumor registry until December 31, 2013. Two cross-sectional surveys on HBV surface antigen (HBsAg) seroprevalence were conducted in 1996–2000 and 2008–2012. The participation rates of the two surveys were 57.5% (21,770) and 50.7% (17,204) in the vaccination group and 36.3% (12,184) and 58.6% (17,395) in the control group, respectively. Using intention-to-treat analysis, we found that the incidence rate of PLC and the mortality rates of severe end-stage liver diseases and infant fulminant hepatitis were significantly lower in the vaccination group than the control group with efficacies of 84% (95% CI 23%–97%), 70% (95% CI 15%–89%), and 69% (95% CI 34%–85%), respectively. The estimated efficacy of catch-up vaccination on HBsAg seroprevalence in early adulthood was 21% (95% CI 10%–30%), substantially weaker than that of the neonatal vaccination (72%, 95% CI 68%–75%). Receiving a booster at age

9 CFR 85.8 - Interstate movement of swine from a qualified negative gene-altered vaccinated herd.

Code of Federal Regulations, 2010 CFR

2010-01-01

... qualified negative gene-altered vaccinated herd. 85.8 Section 85.8 Animals and Animal Products ANIMAL AND... negative gene-altered vaccinated herd. Swine from a qualified negative gene-altered vaccinated herd, and... are from a qualified negative gene-altered vaccinated herd; (2) The date of the herd's last qualifying...

Hepatitis B Vaccine

MedlinePlus

... a combination product containing Haemophilus influenzae type b, Hepatitis B Vaccine) ... combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis, Hepatitis B, Polio Vaccine)

A universal vaccine for serogroup B meningococcus

PubMed Central

Giuliani, Marzia M.; Adu-Bobie, Jeannette; Comanducci, Maurizio; Aricò, Beatrice; Savino, Silvana; Santini, Laura; Brunelli, Brunella; Bambini, Stefania; Biolchi, Alessia; Capecchi, Barbara; Cartocci, Elena; Ciucchi, Laura; Di Marcello, Federica; Ferlicca, Francesca; Galli, Barbara; Luzzi, Enrico; Masignani, Vega; Serruto, Davide; Veggi, Daniele; Contorni, Mario; Morandi, Maurizio; Bartalesi, Alessandro; Cinotti, Vanda; Mannucci, Donatella; Titta, Francesca; Ovidi, Elisa; Welsch, Jo Anne; Granoff, Dan; Rappuoli, Rino; Pizza, Mariagrazia

2006-01-01

Meningitis and sepsis caused by serogroup B meningococcus are two severe diseases that still cause significant mortality. To date there is no universal vaccine that prevents these diseases. In this work, five antigens discovered by reverse vaccinology were expressed in a form suitable for large-scale manufacturing and formulated with adjuvants suitable for human use. The vaccine adjuvanted by aluminum hydroxide induced bactericidal antibodies in mice against 78% of a panel of 85 meningococcal strains representative of the global population diversity. The strain coverage could be increased to 90% and above by the addition of CpG oligonucleotides or by using MF59 as adjuvant. The vaccine has the potential to conquer one of the most devastating diseases of childhood. PMID:16825336

A universal vaccine for serogroup B meningococcus.

PubMed

Giuliani, Marzia M; Adu-Bobie, Jeannette; Comanducci, Maurizio; Aricò, Beatrice; Savino, Silvana; Santini, Laura; Brunelli, Brunella; Bambini, Stefania; Biolchi, Alessia; Capecchi, Barbara; Cartocci, Elena; Ciucchi, Laura; Di Marcello, Federica; Ferlicca, Francesca; Galli, Barbara; Luzzi, Enrico; Masignani, Vega; Serruto, Davide; Veggi, Daniele; Contorni, Mario; Morandi, Maurizio; Bartalesi, Alessandro; Cinotti, Vanda; Mannucci, Donatella; Titta, Francesca; Ovidi, Elisa; Welsch, Jo Anne; Granoff, Dan; Rappuoli, Rino; Pizza, Mariagrazia

2006-07-18

Meningitis and sepsis caused by serogroup B meningococcus are two severe diseases that still cause significant mortality. To date there is no universal vaccine that prevents these diseases. In this work, five antigens discovered by reverse vaccinology were expressed in a form suitable for large-scale manufacturing and formulated with adjuvants suitable for human use. The vaccine adjuvanted by aluminum hydroxide induced bactericidal antibodies in mice against 78% of a panel of 85 meningococcal strains representative of the global population diversity. The strain coverage could be increased to 90% and above by the addition of CpG oligonucleotides or by using MF59 as adjuvant. The vaccine has the potential to conquer one of the most devastating diseases of childhood.

Germinal Center B Cell and T Follicular Helper Cell Responses to Viral Vector and Protein-in-Adjuvant Vaccines

PubMed Central

Wang, Chuan; Hart, Matthew; Chui, Cecilia; Ajuogu, Augustine; Brian, Iona J.; de Cassan, Simone C.; Borrow, Persephone; Draper, Simon J.

2016-01-01

There is great interest in the development of Ab-inducing subunit vaccines targeting infections, including HIV, malaria, and Ebola. We previously reported that adenovirus vectored vaccines are potent in priming Ab responses, but uncertainty remains regarding the optimal approach for induction of humoral immune responses. In this study, using OVA as a model Ag, we assessed the magnitude of the primary and anamnestic Ag–specific IgG responses of mice to four clinically relevant vaccine formulations: replication-deficient adenovirus; modified vaccinia Ankara (a poxvirus); protein with alum; and protein in the squalene oil-in-water adjuvant Addavax. We then used flow cytometric assays capable of measuring total and Ag-specific germinal center (GC) B cell and follicular Th cell responses to compare the induction of these responses by the different formulations. We report that adenovirus vectored vaccines induce Ag insert–specific GC B cell and Ab responses of a magnitude comparable to those induced by a potent protein/squalene oil-in-water formulation whereas—despite a robust overall GC response—the insert-specific GC B cell and Ab responses induced by modified vaccinia Ankara were extremely weak. Ag-specific follicular Th cell responses to adenovirus vectored vaccines exceeded those induced by other platforms at day 7 after immunization. We found little evidence that innate immune activation by adenovirus may act as an adjuvant in such a manner that the humoral response to a recombinant protein may be enhanced by coadministering with an adenovirus lacking a transgene of interest. Overall, these studies provide further support for the use of replication-deficient adenoviruses to induce humoral responses. PMID:27412417

Safety and Immunogenicity of Adenovirus 35 Tuberculosis Vaccine Candidate in Adults with Active or Previous Tuberculosis. A Randomized Trial.

PubMed

van Zyl-Smit, Richard N; Esmail, Aliasgar; Bateman, Mary E; Dawson, Rodney; Goldin, Jonathan; van Rikxoort, Eva; Douoguih, Macaya; Pau, Maria Grazia; Sadoff, Jerald C; McClain, J Bruce; Snowden, Margaret Ann; Benko, Jacqueline; Hokey, David A; Rutkowski, Kathryn Tucker; Graves, Andrew; Shepherd, Barbara; Ishmukhamedov, Sadritdin; Kagina, Benjamin M N; Abel, Brian; Hanekom, Willem A; Scriba, Thomas J; Bateman, Eric D

2017-05-01

Administration of tuberculosis (TB) vaccines in participants with previous or current pulmonary TB may have the potential for causing harmful postvaccination immunologic (Koch-type) reactions. To assess the safety and immunogenicity of three dose levels of the AERAS-402 live, replication-deficient adenovirus 35-vectored TB candidate vaccine, containing three mycobacterial antigens, in individuals with current or previous pulmonary TB. We performed a phase II randomized, placebo-controlled, double-blinded dose-escalation study in an HIV-negative adult South African cohort (n = 72) with active pulmonary TB (on treatment for 1-4 mo) or pulmonary TB treated at least 12 months before study entry and considered cured. Safety endpoints included clinical assessment, flow volume curves, diffusing capacity of the lung for carbon monoxide, pulse oximetry, chest radiograph, and high-resolution thoracic computerized tomography scans. Cytokine expression by CD4 and CD8 T cells, after stimulation with Ag85A, Ag85B, and TB10.4 peptide pools, was examined by intracellular cytokine staining. No apparent temporal or dose-related changes in clinical status (specifically acute, Koch phenomenon-like reactions), lung function, or radiology attributable to vaccine were observed. Injection site reactions were mild or moderate. Hematuria (by dipstick only) occurred in 25 (41%) of 61 AERAS-402 recipients and 3 (27%) of 11 placebo recipients, although no gross hematuria was reported. AERAS-402 induced robust CD8 + and moderate CD4 + T-cell responses, mainly to Ag85B in both vaccine groups. Administration of the AERAS-402 candidate TB vaccine to participants with current or previous pulmonary TB induced a robust immune response and is not associated with clinically significant pulmonary complications. Clinical trial registered with www.clinicaltrials.gov (NCT 02414828) and in the South African National Clinical Trials Register ( www.sanctr.gov.za DOH 27-0808-2060).

Immunogenicity and safety of a high-dose hepatitis B vaccine among patients receiving methadone maintenance treatment: A randomized, double-blinded, parallel-controlled trial.

PubMed

Shi, Jing; Feng, Yongliang; Gao, Linying; Feng, Dan; Yao, Tian; Shi, Shan; Zhang, Yawei; Liang, Xiaofeng; Wang, Suping

2017-04-25

To explore whether the immunization with high-dose (60μg) hepatitis B vaccines in patients receiving methadone maintenance treatment (MMT) could yield a superior protection against hepatitis B infection than did the standard dose (20μg). We conducted a randomized, double-blinded, parallel-controlled trial in MMT patients. Patients with serologically negative hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) were randomized in a ratio of 1:1 to receive three intramuscular injections of 20μg or 60μg recombinant hepatitis B vaccine at months 0, 1, and 6. Serum HBsAg and anti-HBs were measured at months 7 and 12 post-vaccination to assess the immunogenicity. A total of 196 MMT patients were randomized and 195 received at least one injection (98 and 97 in 20 and 60μg vaccine groups, respectively). The 60μg vaccine group showed a seroconversion of anti-HBs of 87.3%, high-level response rate of 56.3%, and GMC of 742.9mIU/mL at month 7. While these results were numerically higher than the 20μg group, a statistical difference was not found. HIV infection and concomitant drug abuse were negatively associated with the robust immune responses. 7.7% of MMT patients receiving at least one dose of vaccine reported solicited adverse reactions within 7days after vaccination, 2.6% reported unsolicited adverse reactions within 28days after vaccination. None of the MMT patients reported serious adverse events or became HBsAg positive during the follow-up. The three-dose regimen of 60μg recombinant hepatitis B vaccine at months 0, 1, and 6 can yield a similar immunogenicity among MMT patients as compared to the 20μg vaccine. ClinicalTrials.gov identifier: NCT02991599. Copyright © 2017. Published by Elsevier Ltd.

Hepatitis B Virus Infection in Indonesia 15 Years After Adoption of a Universal Infant Vaccination Program: Possible Impacts of Low Birth Dose Coverage and a Vaccine-Escape Mutant.

PubMed

Purwono, Priyo Budi; Juniastuti; Amin, Mochamad; Bramanthi, Rendra; Nursidah; Resi, Erika Maria; Wahyuni, Rury Mega; Yano, Yoshihiko; Soetjipto; Hotta, Hak; Hayashi, Yoshitake; Utsumi, Takako; Lusida, Maria Inge

2016-09-07

A universal hepatitis B vaccination program for infants was adopted in Indonesia in 1997. Before its implementation, the prevalence of hepatitis B surface antigen (HBsAg)-positive individuals in the general population was approximately 5-10%. The study aimed to investigate the hepatitis B virus (HBV) serological status and molecular profile among children, 15 years after adoption of a universal infant vaccination program in Indonesia. According to the Local Health Office data in five areas, the percentages of children receiving three doses of hepatitis B vaccine are high (73.9-94.1%), whereas the birth dose coverage is less than 50%. Among 967 children in those areas, the seropositive rate of HBsAg in preschool- and school-aged children ranged from 2.1% to 4.2% and 0% to 5.9%, respectively. Of the 61 HBV DNA-positive samples, the predominant genotype/subtype was B/adw2 Subtype adw3 was identified in genotype C for the first time in this population. Six samples (11.5%) had an amino acid substitution within the a determinant of the S gene region, and one sample had T140I that was suggested as a vaccine-escape mutant type. The low birth dose coverage and the presence of a vaccine-escape mutant might contribute to the endemicity of HBV infection among children in Indonesia. © The American Society of Tropical Medicine and Hygiene.

Hepatitis B Virus Infection in Indonesia 15 Years after Adoption of a Universal Infant Vaccination Program: Possible Impacts of Low Birth Dose Coverage and a Vaccine-Escape Mutant

PubMed Central

Purwono, Priyo Budi; Juniastuti; Amin, Mochamad; Bramanthi, Rendra; Nursidah; Resi, Erika Maria; Wahyuni, Rury Mega; Yano, Yoshihiko; Soetjipto; Hotta, Hak; Hayashi, Yoshitake; Utsumi, Takako; Lusida, Maria Inge

2016-01-01

A universal hepatitis B vaccination program for infants was adopted in Indonesia in 1997. Before its implementation, the prevalence of hepatitis B surface antigen (HBsAg)–positive individuals in the general population was approximately 5–10%. The study aimed to investigate the hepatitis B virus (HBV) serological status and molecular profile among children, 15 years after adoption of a universal infant vaccination program in Indonesia. According to the Local Health Office data in five areas, the percentages of children receiving three doses of hepatitis B vaccine are high (73.9–94.1%), whereas the birth dose coverage is less than 50%. Among 967 children in those areas, the seropositive rate of HBsAg in preschool- and school-aged children ranged from 2.1% to 4.2% and 0% to 5.9%, respectively. Of the 61 HBV DNA–positive samples, the predominant genotype/subtype was B/adw2. Subtype adw3 was identified in genotype C for the first time in this population. Six samples (11.5%) had an amino acid substitution within the a determinant of the S gene region, and one sample had T140I that was suggested as a vaccine-escape mutant type. The low birth dose coverage and the presence of a vaccine-escape mutant might contribute to the endemicity of HBV infection among children in Indonesia. PMID:27402524

Acute Hepatitis B After the Implementation of Universal Vaccination in Italy: Results From 22 Years of Surveillance (1993-2014).

PubMed

Tosti, Maria Elena; Alfonsi, Valeria; Lacorte, Eleonora; Mele, Alfonso; Galli, Cristina; Zanetti, Alessandro Remo; Romanò, Luisa

2016-06-01

Hepatitis B vaccination has proven to be very safe and highly effective. This study assessed the proportion of successfully vaccinated individuals among cases with acute hepatitis B, the proportion of preventable cases if individuals were vaccinated as recommended, and the reasons for failures. We analyzed data reported to the Italian Surveillance System for Acute Viral Hepatitis from 1993 to 2014. A total of 362 of 11 311 (3.2%) cases with acute hepatitis B were vaccinated. Of the 277 cases for whom immunization data were available, 50 (18%) received a complete vaccination course according to the correct schedule and before exposure to hepatitis B virus. Molecular characterization of 17 of these cases showed that 6 were infected with S-gene mutants. Among the 10 949 unvaccinated cases, 213 (1.9%) escaped mandatory vaccination and 2821 (25.8%) were not vaccinated despite being at increased risk of infection. Among the latter, the most common risk factors were cohabitation with hepatitis B surface antigen (HBsAg) carriers, intravenous drug use, and homosexual/bisexual practices. Thirty-seven percent of the unvaccinated households with HBsAg carriers were aware of their risk. Lack of trust in the vaccination, negative attitude, and inaccurate beliefs followed by lack of or poor communication and low perceived severity of the disease were the most frequent reasons for vaccine hesitancy. Development of acute disease in successfully vaccinated individuals is a rare event. Further efforts are needed to enhance the vaccine coverage rate in individuals at increased risk of infection. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Effect of a polysaccharide from Poria cocos on humoral response in mice immunized by H1N1 influenza and HBsAg vaccines.

PubMed

Wu, Yajun; Li, Shuai; Li, Haixia; Zhao, Chunzhi; Ma, Hao; Zhao, Xiunan; Wu, Junhua; Liu, Kunlu; Shan, Junjie; Wang, Yuxia

2016-10-01

Poria cocos has a long history of medicinal use in China. Polysaccharides and their derivatives in the medicine exhibit many beneficial biological activities including anticancer, anti-inflammatory, antioxidant and antiviral activities. In this study, a new polysaccharide (PCP-II) was isolated from sclerotium of Poria cocos. Its physico-chemical characters were identified and its adjuvant activity was investigated in mice co-immunized with H1N1 influenza vaccine and hepatitis B surface antigen (HBsAg). The results revealed that PCP-II has a molecular weight of 29.0kDa. It was composed of fucose, mannose, glucose and galactose in molar ration of 1.00:1.63:0.16:6.29 respectively. Pharmacological data demonstrated that PCP-II increased antigen-specific antibody levels in mice immunized with influenza vaccine. PCP-II also elicited anti-HBsAg antibodies at significantly higher titers and generated robust and durable immunity compared to mice immunized with HBsAg-alum following two administrations. PCP-II improved proliferation of splenocytes, stimulated IL-12p70 and TNF-α productions in dendritic cells and macrophages respectively. These results suggested that PCP-II-adjuvanted vaccines enhanced humoral and cellular immunity. PCP-II could be developed as an efficacious adjuvant in human and animal vaccines. Copyright © 2016 Elsevier B.V. All rights reserved.

B cells from knock-in mice expressing broadly neutralizing HIV antibody b12 carry an innocuous B cell receptor responsive to HIV vaccine candidates.

PubMed

Ota, Takayuki; Doyle-Cooper, Colleen; Cooper, Anthony B; Doores, Katherine J; Aoki-Ota, Miyo; Le, Khoa; Schief, William R; Wyatt, Richard T; Burton, Dennis R; Nemazee, David

2013-09-15

Broadly neutralizing Abs against HIV protect from infection, but their routine elicitation by vaccination has not been achieved. To generate small animal models to test vaccine candidates, we have generated targeted transgenic ("knock-in") mice expressing, in the physiological Ig H and L chain loci, two well-studied broadly neutralizing Abs: 4E10, which interacts with the membrane proximal external region of gp41, and b12, which binds to the CD4 binding site on gp120. 4E10HL mice are described in the companion article (Doyle-Cooper et al., J. Immunol. 191: 3186-3191). In this article, we describe b12 mice. B cells in b12HL mice, in contrast to the case in 4E10 mice, were abundant and essentially monoclonal, retaining the b12 specificity. In cell culture, b12HL B cells responded avidly to HIV envelope gp140 trimers and to BCR ligands. Upon transfer to wild-type recipients, b12HL B cells responded robustly to vaccination with gp140 trimers. Vaccinated b12H mice, although generating abundant precursors and Abs with affinity for Env, were unable to rapidly generate neutralizing Abs, highlighting the importance of developing Ag forms that better focus responses to neutralizing epitopes. The b12HL and b12H mice should be useful in optimizing HIV vaccine candidates to elicit a neutralizing response while avoiding nonprotective specificities.

Molecular epidemiology and genotyping of hepatitis B virus of HBsAg-positive patients in Oman.

PubMed

Al Baqlani, Said Ali; Sy, Bui Tien; Ratsch, Boris A; Al Naamani, Khalid; Al Awaidy, Salah; Busaidy, Suleiman Al; Pauli, Georg; Bock, C-Thomas

2014-01-01

Hepatitis B virus (HBV) infection is a major global health burden with distinct geographic public health significance. Oman is a country with intermediate HBV carrier prevalence; however, little is known about the incidence of HBV variants in circulation. We investigated the HBV genotype distribution, the occurrence of antiviral resistance, and HBV surface antigen (HBsAg) escape mutations in HBsAg-positive patients in Oman. Serum samples were collected from 179 chronically HBV-infected patients enrolled in various gastroenterology clinics in Oman. HBV genotypes were determined by sequencing and phylogenetic analysis. Mutations in the HBV polymerase and the HBsAg gene were characterized by mutational analysis. HBV genotypes D (130/170; 76.47%) and A (32/170; 18.28%) are predominant in Oman. The HBV genotypes C and E were less frequent (each 1.18%), while the HBV genotypes B, G, F, and H were not detected. Four patients revealed HBV genotype mixtures (HBV-A/D and D/C). The analyses of vaccine escape mutations yield that 148/170 (87.06%) HBV sequences were wild type. 22/170 (12.94%) HBV sequences showed mutations in the "a" determinant of the HBsAg domain. Two patients showed the described HBV vaccine escape mutation sP120T. 8/146 (5.48%) HBV isolates harbored mutations in the HBV polymerase known to confer resistance against antiviral therapy. Especially the lamivudine resistance mutations rtL180M/rtM204V and rtM204I were detected. This study shows the distribution of HBV genotypes, therapy resistance, and vaccine escape mutations in HBV-infected patients in Oman. Our findings will have a major impact on therapy management and diagnostics of chronic HBV infections in Oman to control HBV infection in this intermediate HBV-endemic country.

Molecular Epidemiology and Genotyping of Hepatitis B Virus of HBsAg-Positive Patients in Oman

PubMed Central

Al Naamani, Khalid; Al Awaidy, Salah; Busaidy, Suleiman Al; Pauli, Georg; Bock, C.-Thomas

2014-01-01

Background Hepatitis B virus (HBV) infection is a major global health burden with distinct geographic public health significance. Oman is a country with intermediate HBV carrier prevalence; however, little is known about the incidence of HBV variants in circulation. We investigated the HBV genotype distribution, the occurrence of antiviral resistance, and HBV surface antigen (HBsAg) escape mutations in HBsAg-positive patients in Oman. Methods Serum samples were collected from 179 chronically HBV-infected patients enrolled in various gastroenterology clinics in Oman. HBV genotypes were determined by sequencing and phylogenetic analysis. Mutations in the HBV polymerase and the HBsAg gene were characterized by mutational analysis. Results HBV genotypes D (130/170; 76.47%) and A (32/170; 18.28%) are predominant in Oman. The HBV genotypes C and E were less frequent (each 1.18%), while the HBV genotypes B, G, F, and H were not detected. Four patients revealed HBV genotype mixtures (HBV-A/D and D/C). The analyses of vaccine escape mutations yield that 148/170 (87.06%) HBV sequences were wild type. 22/170 (12.94%) HBV sequences showed mutations in the “a” determinant of the HBsAg domain. Two patients showed the described HBV vaccine escape mutation sP120T. 8/146 (5.48%) HBV isolates harbored mutations in the HBV polymerase known to confer resistance against antiviral therapy. Especially the lamivudine resistance mutations rtL180M/rtM204V and rtM204I were detected. Conclusion This study shows the distribution of HBV genotypes, therapy resistance, and vaccine escape mutations in HBV-infected patients in Oman. Our findings will have a major impact on therapy management and diagnostics of chronic HBV infections in Oman to control HBV infection in this intermediate HBV-endemic country. PMID:24835494

Persistence of antibodies 20 y after vaccination with a combined hepatitis A and B vaccine

PubMed Central

Van Damme, Pierre; Leroux-Roels, Geert; Suryakiran, P.; Folschweiller, Nicolas; Van Der Meeren, Olivier

2017-01-01

ABSTRACT Vaccination is the most effective and well-tolerated method of conferring long-term protection against hepatitis A and B viruses (HAV; HBV). Long-term studies are required to characterize the duration of protection and need for boosters. Following primary immunization of 150 and 157 healthy adults with 3-doses of combined hepatitis A/hepatitis B vaccine (HAB; Twinrix™, GSK Vaccines, Belgium) at 0-1-6 months in 2 separate studies, we measured vaccine-induced antibody persistence against HAV and HBV annually for 20 y (Study A: NCT01000324; Study B: NCT01037114). Subjects with circulating anti-HAV antibodies < 15 mIU/mL or with anti-hepatitis B surface antigen < 10 mIU/mL were offered an additional monovalent hepatitis A and/or B vaccine dose (Havrix™/Engerix™-B, GSK Vaccines, Belgium). Applying the immunogenicity results from these studies, mathematical modeling predicted long-term persistence. After 20 y, 18 and 25 subjects in studies A and B, respectively, comprised the long-term according-to-protocol cohort for immunogenicity; 100% and 96.0% retained anti-HAV antibodies ≥ 15 mIU/mL, respectively; 94.4% and 92.0% had anti-HBs antibodies ≥ 10 mIU/mL, respectively. Between Years 16–20, 4 subjects who received a challenge dose of monovalent hepatitis A vaccine (N = 2) or hepatitis B vaccine (N = 2), all mounted a strong anamnestic response suggestive of immune memory despite low antibody levels. Mathematical modeling predicts that 40 y after vaccination ≥ 97% vaccinees will maintain anti-HAV ≥ 15 mIU/mL and ≥ 50% vaccinees will retain anti-HBs ≥ 10 mIU/mL. Immunogenicity data confirm that primary immunization with 3-doses of HAB induces persisting anti-HAV and anti-HBs specific antibodies in most adults for up to 20 y; mathematical modeling predicts even longer-term protection. PMID:28281907

Persistence of antibodies 20 y after vaccination with a combined hepatitis A and B vaccine.

PubMed

Van Damme, Pierre; Leroux-Roels, Geert; Suryakiran, P; Folschweiller, Nicolas; Van Der Meeren, Olivier

2017-05-04

Vaccination is the most effective and well-tolerated method of conferring long-term protection against hepatitis A and B viruses (HAV; HBV). Long-term studies are required to characterize the duration of protection and need for boosters. Following primary immunization of 150 and 157 healthy adults with 3-doses of combined hepatitis A/hepatitis B vaccine (HAB; Twinrix™, GSK Vaccines, Belgium) at 0-1-6 months in 2 separate studies, we measured vaccine-induced antibody persistence against HAV and HBV annually for 20 y (Study A: NCT01000324; Study B: NCT01037114). Subjects with circulating anti-HAV antibodies < 15 mIU/mL or with anti-hepatitis B surface antigen < 10 mIU/mL were offered an additional monovalent hepatitis A and/or B vaccine dose (Havrix™/Engerix™-B, GSK Vaccines, Belgium). Applying the immunogenicity results from these studies, mathematical modeling predicted long-term persistence. After 20 y, 18 and 25 subjects in studies A and B, respectively, comprised the long-term according-to-protocol cohort for immunogenicity; 100% and 96.0% retained anti-HAV antibodies ≥ 15 mIU/mL, respectively; 94.4% and 92.0% had anti-HBs antibodies ≥ 10 mIU/mL, respectively. Between Years 16-20, 4 subjects who received a challenge dose of monovalent hepatitis A vaccine (N = 2) or hepatitis B vaccine (N = 2), all mounted a strong anamnestic response suggestive of immune memory despite low antibody levels. Mathematical modeling predicts that 40 y after vaccination ≥ 97% vaccinees will maintain anti-HAV ≥ 15 mIU/mL and ≥ 50% vaccinees will retain anti-HBs ≥ 10 mIU/mL. Immunogenicity data confirm that primary immunization with 3-doses of HAB induces persisting anti-HAV and anti-HBs specific antibodies in most adults for up to 20 y; mathematical modeling predicts even longer-term protection.

Long-term effectiveness of plasma-derived hepatitis B vaccine 22-28 years after immunization in a hepatitis B virus endemic rural area: is an adult booster dose needed?

PubMed

Li, H; Li, G J; Chen, Q Y; Fang, Z L; Wang, X Y; Tan, C; Yang, Q L; Wang, F Z; Wang, F; Zhang, S; Bi, S L; Shen, L P

2017-04-01

Longan County is considered a highly endemic area for hepatitis B virus (HBV). The plasma-derived vaccine has been used in newborns in this area since 1987. A cross-sectional survey was conducted to evaluate the long-term effectiveness of this vaccine. In total, 1634 participants born during 1987-1993 and who had received a series of plasma-derived HB vaccinations at ages 0, 1, and 6 months were enrolled. Serological HBV markers were detected and compared with previous survey data. Overall the prevalence of hepatitis B surface antigen (HBsAg) in all participants was 3·79%; 3·47% of subjects who had received the first dose within 24 h were HBsAg positive, and 8·41% of subjects who had received a delayed first dose were also HBsAg positive. There were 1527 subjects identified who had received the first dose within 24 h and whose HBsAg and anti-HBc prevalence increased yearly after immunization, while the anti-HBs-positive rate and vaccine effectiveness declined. The geometric mean concentration of antibody in the anti-HB-positive participants was 55·13 mIU/ml and this declined after immunization. Fewer than 2·0% of participants had anti-HB levels ⩾1000 mIU/ml. The data show that the protective efficacy of the plasma-derived vaccinations declined and administration of HB vaccine within 24 h of birth was very important. To reduce the risk of HBV infection in this highly endemic area, a booster dose might be necessary if anti-HBs levels fall below 10 mIU/ml after age 18 years. Furthermore, studies on the immune memory induced by plasma-derived HB vaccine are needed.

Intranasal mucosal boosting with an adenovirus-vectored vaccine markedly enhances the protection of BCG-primed guinea pigs against pulmonary tuberculosis.

PubMed

Xing, Zhou; McFarland, Christine T; Sallenave, Jean-Michel; Izzo, Angelo; Wang, Jun; McMurray, David N

2009-06-10

Recombinant adenovirus-vectored (Ad) tuberculosis (TB) vaccine platform has demonstrated great potential to be used either as a stand-alone or a boost vaccine in murine models. However, Ad TB vaccine remains to be evaluated in a more relevant and sensitive guinea pig model of pulmonary TB. Many vaccine candidates shown to be effective in murine models have subsequently failed to pass the test in guinea pig models. Specific pathogen-free guinea pigs were immunized with BCG, AdAg85A intranasally (i.n), AdAg85A intramuscularly (i.m), BCG boosted with AdAg85A i.n, BCG boosted with AdAg85A i.m, or treated only with saline. The animals were then infected by a low-dose aerosol of M. tuberculosis (M.tb). At the specified times, the animals were sacrificed and the levels of infection in the lung and spleen were assessed. In separate studies, the long-term disease outcome of infected animals was monitored until the termination of this study. Immunization with Ad vaccine alone had minimal beneficial effects. Immunization with BCG alone and BCG prime-Ad vaccine boost regimens significantly reduced the level of M.tb infection in the tissues to a similar extent. However, while BCG alone prolonged the survival of infected guinea pigs, the majority of BCG-immunized animals succumbed by 53 weeks post-M.tb challenge. In contrast, intranasal or intramuscular Ad vaccine boosting of BCG-primed animals markedly improved the survival rate with 60% of BCG/Ad i.n- and 40% of BCG/Ad i.m-immunized guinea pigs still surviving by 74 weeks post-aerosol challenge. Boosting, particularly via the intranasal mucosal route, with AdAg85A vaccine is able to significantly enhance the long-term survival of BCG-primed guinea pigs following pulmonary M.tb challenge. Our results thus support further evaluation of this viral-vectored TB vaccine in clinical trials.

Genetic variation of hepatitis B surface antigen among acute and chronic hepatitis B virus infections in The Netherlands.

PubMed

Cremer, Jeroen; Hofstraat, Sanne H I; van Heiningen, Francoise; Veldhuijzen, Irene K; van Benthem, Birgit H B; Benschop, Kimberley S M

2018-05-24

Genetic variation within hepatitis B surface antigen (HBsAg), in particular within the major hydrophobic region (MHR), is related to immune/vaccine and test failures and can have a significant impact on the vaccination and diagnosis of acute infection. This study shows, for the first time, variation among acute cases and compares the amino acid variation within the HBsAg between acute and chronic infections. We analyzed the virus isolated from 1231 acute and 585 chronic cases reported to an anonymized public health surveillance database between 2004 and 2014 in The Netherlands. HBsAg analysis revealed the circulation of 6 genotypes (Gt); GtA was the dominant genotype followed by GtD among both acute (68.2% and 17.4%, respectively) and chronic (34.9% and 34.2%, respectively) cases. Variation was the highest among chronic strains compared to that among acute strains. Both acute and chronic GtD showed the highest variation compared to that of other genotypes (P < .01). Substitutions within the MHR were found in 8.5% of the acute strains and 18.6% of the chronic strains. Specific MHR substitutions described to have an impact on vaccine/immune escape and/or HBsAg test failure were found among 4.1% of the acute strains and 7.0% of the chronic strains. In conclusion, we show a high variation of HBsAg among acute and chronic hepatitis B virus-infected cases in The Netherlands, in particular among those infected with GtD, and compare, for the first time, variation in frequencies between acute and chronic cases. Additional studies on the impact of these variations on vaccination and test failure need to be conducted, as well as whether HBsAg false-negative variants have been missed. © 2018 The Authors. Journal of Medical Virology Published by Wiley Periodicals, Inc.

Hepatitis B infection control in Colombian Amazon after 15 years of hepatitis B vaccination. Effectiveness of birth dose and current prevalence.

PubMed

Garcia, Diego; Porras, Alexandra; Rico Mendoza, Alejadro; Alvis, Nelson; Navas, Maria Cristina; De La Hoz, Fernando; De Neira, Marlen; Osorio, Elkin; Valderrama, José Fernando

2018-05-03

Hepatitis B virus (HBV) infection is highly endemic in the Colombian Amazon basin. In Colombia, the universal hepatitis B vaccination in that area has been active since 1993. The program targets children aged under five years. Newborns receive at least three doses, and in 2001, HBV vaccine birth dose was included. This study aimed to evaluate the advances on HBV control in the Colombian Amazon. A population-based cross-sectional study was conducted in children less than 11 years old in rural areas of the Colombian Amazon, in order to assess the current levels of HBV prevalence and evaluate the effectiveness of HBV vaccination. Participants were selected from villages scattered along the Amazon, Putumayo and Loretoyaco Rivers. Blood samples were taken from children. All the samples were examined for surface antigen (HBsAg) and IgG antibodies against core antigen (AntiHBc) of HBV. Data on HBV vaccination status and other risk factors were also collected. Blood samples from 1275 children were included in the study. The positivity for IgG AntiHBC and HBsAg was 3.8% and 0.5%, respectively. It was observed that receiving a dose of HBV vaccine within 48 h after birth decreased the risk of HBV infection and carriage by 95%. Being born to an AntiHBc positive mother increased 8 times the risk of HBV infection (OR = 7.8 CI 95% 3.3-10.2) and 7 times the risk of HBsAg carriage (OR = 6.6 CI 95% 2.1-10.1). The prevalence of HBV infection and HBsAg carriage continues to decrease among children living in the Colombian Amazon. The high protective effectiveness of an HBV birth does suggest that perinatal transmission is important in endemic areas of Latin America, an aspect that has not been fully studied in the region. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Prokaryotic expression and immunological characteristics of Mycobacterium tuberculosis Rv1886c].

PubMed

Tao, Chengwu; Zhao, Dan; Dong, Hui; Shan, Fa; Lian, Kai; Pan, Zhiming; Chen, Xiang; Yin, Yuelan; Jiao, Xin'an

2014-03-04

Ag85B (Rv1886c) is secreted during the early stages of infection by Mycobacterium tuberculosis. The purpose of this study was probed into the immune response against Ag85B in vivo. Ag85B was prokaryotic expressed and identified, its immunological characteristics were evaluated with indirect-ELSIA, Sandwich-ELISA and Ag85B was mainly expressed in form of inclusion body enzyme-linked immunospot assay (ELISPOT). confirmed by SDS-PAGE. Western blot analysis shows that the fusion protein had good specific reaction with serum of tuberculosis patient and serum of mice immunized with LM-Ag85B. C57BL/6 mice were subcutaneously immunized with Ag85B, the production of IFN-gamma and IL-4 in the spleen cells was determined by Sandwich ELISA, the level of IFN-gamma was significantly higher than that of IL-4 (P < 0.001) in the Ag85B immunization group, it indicated the protein induced Th1-tendency immune responses. Furthermore, purified protein derivative (PPD) used as coating antigen, antibody titer against Ag85B in murine serum reached 1:6400, it was demonstrated that Ag85B could also induce humoral immune responses. Additionally, C57BL/6 mice were intravenously immunized with M. tb H37Rv and bacillus Calmette-Guérin (BCG) respectively for 42 days, M. tb H37Rv group intended to induce Ag85B specific Th1 type immune response, and its ability of eliciting cellular immunity was significantly stronger than BCG group (P < 0.001). Ag85B can affectively induce strongly Th1-tendency immune response and humoral response. Whereas, BCG prime vaccination only can elicit low levels of Ag85B(240-259) specific immune response. The study laid foundation for probing the pathogenic mechanism, the development of novel vaccine and the establishment of clinical diagnostic method.

Efficacy of intranasal LaAg vaccine against Leishmania amazonensis infection in partially resistant C57Bl/6 mice.

PubMed

Pratti, Juliana Elena Silveira; Ramos, Tadeu Diniz; Pereira, Joyce Carvalho; da Fonseca-Martins, Alessandra Marcia; Maciel-Oliveira, Diogo; Oliveira-Silva, Gabriel; de Mello, Mirian França; Chaves, Suzana Passos; Gomes, Daniel Claudio Oliveira; Diaz, Bruno Lourenço; Rossi-Bergmann, Bartira; de Matos Guedes, Herbert Leonel

2016-10-06

We have previously demonstrated that intranasal vaccination of highly susceptible BALB/c mice with whole Leishmania amazonensis antigens (LaAg) leads to protection against murine cutaneous leishmaniasis. Here, we evaluate the response of partially resistant C57BL/6 mice to vaccination as a more representative experimental model of human cutaneous leishmaniasis. C57BL/6 mice from different animal facilities were infected with L. amazonensis (Josefa strain) to establish the profile of infection. Intranasal vaccination was performed before the infection challenge with two doses of 10 μg of LaAg alone or associated with the adjuvant ADDAVAX® by instillation in the nostrils. The lesion progression was measured with a dial caliper and the parasite load by limited dilution assay in the acute and chronic phases of infection. Cytokines were quantified by ELISA in the homogenates of infected footpads. C57BL/6 mice from different animal facilities presented the same L. amazonensis infection profile, displaying a progressive acute phase followed by a controlled chronic phase. Parasites cultured in M199 and Schneider's media were equally infective. Intranasal vaccination with LaAg led to milder acute and chronic phases of the disease. The mechanism of protection was associated with increased production of IFN-gamma in the infected tissue as measured in the acute phase. Association with the ADDAVAX® adjuvant did not improve the efficacy of intranasal LaAg vaccination. Rather, ADDAVAX® reduced vaccination efficacy. This study demonstrates that the efficacy of adjuvant-free intranasal vaccination with LaAg is extendable to the more resistant C57Bl/6 mouse model of infection with L. amazonensis, and is thus not exclusive to the susceptible BALB/c model. These results imply that mucosal immunomodulation by LaAg leads to peripheral protection irrespective of the genetic background of the host.

Enoyl-Coenzyme A Hydratase and Antigen 85B of Mycobacterium habana Are Specifically Recognized by Antibodies in Sera from Leprosy Patients ▿

PubMed Central

Serafín-López, J.; Talavera-Paulin, M.; Amador-Molina, J. C.; Alvarado-Riverón, M.; Vilchis-Landeros, M. M.; Méndez-Ortega, P.; Fafutis-Morris, M.; Paredes-Cervantes, V.; López-Santiago, R.; León, C. I.; Guerrero, M. I.; Ribas-Aparicio, R. M.; Mendoza-Hernández, G.; Carreño-Martínez, C.; Estrada-Parra, S.; Estrada-García, I.

2011-01-01

Leprosy is an infectious disease caused by Mycobacterium leprae, which is a noncultivable bacterium. One of the principal goals of leprosy research is to develop serological tests that will allow identification and early treatment of leprosy patients. M. habana is a cultivable nonpathogenic mycobacterium and candidate vaccine for leprosy, and several antigens that cross-react between M. leprae and M. habana have been discovered. The aim of the present study was to extend the identification of cross-reactive antigens by identifying M. habana proteins that reacted by immunoblotting with antibodies in serum samples from leprosy patients but not with antibodies in sera from tuberculosis (TB) patients or healthy donors (HDs). A 28-kDa antigen that specifically reacted with sera from leprosy patients was identified. To further characterize this antigen, protein spots were aligned in two-dimensional polyacrylamide gels and Western blots. Spots cut out from the gels were then analyzed by mass spectrometry. Two proteins were identified: enoyl-coenzyme A hydratase (lipid metabolism; ML2498) and antigen 85B (Ag85B; mycolyltransferase; ML2028). These proteins represent promising candidates for the design of a reliable tool for the serodiagnosis of lepromatous leprosy, which is the most frequent form in Mexico. PMID:21613461

Overcoming immune tolerance in chronic hepatitis B by therapeutic vaccination.

PubMed

Dembek, Claudia; Protzer, Ulrike; Roggendorf, Michael

2018-05-08

The currently used nucleoside analogs (i.e. entecavir and tenofovir) with high barrier-to-resistance efficiently suppress viral replication, limit inflammation and reduce the sequelae of chronic hepatitis B, but cannot cure the disease and thus have to be applied long-term. Therapeutic vaccination as an approach to cure chronic hepatitis B has shown promising pre-clinical results, nevertheless the proof of its efficacy in clinical trials is still missing. This may be partially due to suboptimal vaccine design. A main obstacle in chronic hepatitis B, however, is the high load of viral antigens expressed and secreted, which has been proposed to cause antigen-specific immune tolerance. Reduction of the viral antigen load is therefore considered a key factor for success of immune-based therapies. Although nucleoside analogs do not reduce viral antigen expression, new antiviral strategies are becoming available. Targeting viral translation by siRNA or targeting release of HBsAg from infected hepatocytes by nucleic acid polymers both reduce the antigen load. They may be considered as pre-treatment for therapeutic vaccination to increase the potential to elicit an HBV-specific immune response able to control and cure chronic HBV infection. Copyright © 2018 Elsevier B.V. All rights reserved.

Protective efficacy of Zika vaccine in AG129 mouse model

PubMed Central

Sumathy, K.; Kulkarni, Bharathi; Gondu, Ravi Kumar; Ponnuru, Sampath Kumar; Bonguram, Nagaraju; Eligeti, Rakesh; Gadiyaram, Sindhuja; Praturi, Usha; Chougule, Bhushan; Karunakaran, Latha; Ella, Krishna M.

2017-01-01

Zika virus (ZIKV) is a mosquito-borne flavivirus that causes asymptomatic infection or presents only mild symptoms in majority of those infected. However, vaccination for ZIKV is a public health priority due to serious congenital and neuropathological abnormalities observed as a sequelae of the virus infection in the recent epidemics. We have developed an inactivated virus vaccine with the African MR 766 strain. Here we show that two doses of the vaccine provided 100% efficacy against mortality and disease following challenge with homotypic MR 766 and the heterotypic FSS 13025 ZIKV strains in the Type I and Type II interferon deficient AG129 mice. Two doses of the vaccine elicited high titer of neutralizing antibodies in Balb/c mice, and the vaccine antisera conferred protection against virus challenge in passively immunized mice. The studies were useful to rationalize vaccine doses for protective efficacy. Furthermore, the vaccine antisera neutralized the homotypic and heterotypic ZIKV strains in vitro with equivalent efficiency. Our study suggests a single ZIKV serotype, and that the development of an effective vaccine may not be limited by the choice of virus strain. PMID:28401907

Protective efficacy of Zika vaccine in AG129 mouse model.

PubMed

Sumathy, K; Kulkarni, Bharathi; Gondu, Ravi Kumar; Ponnuru, Sampath Kumar; Bonguram, Nagaraju; Eligeti, Rakesh; Gadiyaram, Sindhuja; Praturi, Usha; Chougule, Bhushan; Karunakaran, Latha; Ella, Krishna M

2017-04-12

Zika virus (ZIKV) is a mosquito-borne flavivirus that causes asymptomatic infection or presents only mild symptoms in majority of those infected. However, vaccination for ZIKV is a public health priority due to serious congenital and neuropathological abnormalities observed as a sequelae of the virus infection in the recent epidemics. We have developed an inactivated virus vaccine with the African MR 766 strain. Here we show that two doses of the vaccine provided 100% efficacy against mortality and disease following challenge with homotypic MR 766 and the heterotypic FSS 13025 ZIKV strains in the Type I and Type II interferon deficient AG129 mice. Two doses of the vaccine elicited high titer of neutralizing antibodies in Balb/c mice, and the vaccine antisera conferred protection against virus challenge in passively immunized mice. The studies were useful to rationalize vaccine doses for protective efficacy. Furthermore, the vaccine antisera neutralized the homotypic and heterotypic ZIKV strains in vitro with equivalent efficiency. Our study suggests a single ZIKV serotype, and that the development of an effective vaccine may not be limited by the choice of virus strain.

Safety and immunogenicity of a modified process hepatitis B vaccine in healthy neonates.

PubMed

Minervini, Gianmaria; McCarson, Barbara J; Reisinger, Keith S; Martin, Jason C; Stek, Jon E; Atkins, Barbara M; Nadig, Karin B; Liska, Vladimir; Schödel, Florian P; Bhuyan, Prakash K

2012-02-14

A manufacturing process using a modified adjuvant was developed to optimize the consistency and immunogenicity for recombinant hepatitis B vaccine (control: RECOMBIVAX-HB™). This modified process hepatitis B vaccine (mpHBV), which was previously shown to have an acceptable safety and immunogenicity profile in young adults, has now been studied in newborn infants. Healthy 1-10-day-old neonates (N=566) received 3 intramuscular doses (5μg hepatitis B surface antigen [HBsAg] per dose) of either mpHBV or control at Day 1, and Months 1 and 6. Serum antibody to HBsAg (anti-HBs) was assayed at Month 7 (1 month Postdose 3). Anti-HBs geometric mean titers (GMTs) and seroprotection rates (SPRs) (% of subjects with an anti-HBs titer ≥10mIU/mL) were compared at Month 7. After each dose, injection-site adverse experiences (AEs) and axillary temperatures were recorded for 5 days; systemic AEs were recorded for Days 1-14. Month 7 SPR was 97.9% for the mpHBV group and 98.9% for the control. The GMT was 843.7mIU/mL for the mpHBV group and 670.1mIU/mL for the control. The GMT ratio (mpHBV/control) was 1.26 (95% confidence interval [CI]: 0.94, 1.69), meeting the prespecified non-inferiority criteria. The percentages of subjects reporting any AE, injection-site AEs, or systemic AEs were similar across the 2 vaccination groups. There were no serious AEs. The safety profile of mpHBV was comparable to that of the control vaccine. The geometric mean antibody titer for mpHBV was higher than control vaccine in this infant population, but the difference did not meet the predefined statistical criterion for superiority. Copyright © 2012 Elsevier Ltd. All rights reserved.

Comparison of the immunogenicity and protection against bovine tuberculosis following immunization by BCG-priming and boosting with adenovirus or protein based vaccines.

PubMed

Dean, G; Whelan, A; Clifford, D; Salguero, F J; Xing, Z; Gilbert, S; McShane, H; Hewinson, R G; Vordermeier, M; Villarreal-Ramos, B

2014-03-05

There is a requirement for vaccines or vaccination strategies that confer better protection against TB than the current live attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccine for use in cattle. Boosting with recombinant viral vectors expressing mycobacterial proteins, such as Ag85A, has shown a degree of promise as a strategy for improving on the protection afforded by BCG. Experiments in small animal models have indicated that broadening the immune response to include mycobacterial antigens other than Ag85A, such as Rv0288, induced by boosting with Ad5 constructs has a direct effect on the protection afforded against TB. Here, we compared the immunogenicity and protection against challenge with M. bovis afforded by boosting BCG-vaccinated cattle with a human type 5 (Ad5)-based vaccine expressing the mycobacterial antigens Ag85A (Ad5-85A); or Ag85A, Rv0251, Rv0287 and Rv0288 (Ad5-TBF); or with protein TBF emulsified in adjuvant (Adj-TBF). Boosting with TBF broaden the immune response. The kinetics of Ad5-TBF and Adj-TBF were shown to be different, with effector T cell responses from the latter developing more slowly but being more durable than those induced by Ad5-TBF. No increase in protection compared to BCG alone was afforded by Ad5-TBF or Adj-TBF by gross pathology or bacteriology. Using histopathology, as a novel parameter of protection, we show that boosting BCG vaccinated cattle with Ad5-85A induced significantly better protection than BCG alone. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Clinical and Virological Characteristics of Chronic Hepatitis B Patients with Coexistence of HBsAg and Anti-HBs.

PubMed

Liu, Yong; Zhang, Le; Zhou, Jin-Yong; Pan, Jinshun; Hu, Wei; Zhou, Yi-Hua

2016-01-01

Coexistence of hepatitis B surface antigen (HBsAg) and antibody against HBsAg (anti-HBs) comprises an atypical serological profile in patients with chronic hepatitis B virus (HBV) infection. In this study, in total 94 patients with coexisting HBsAg and anti-HBs and 94 age- and sex-matched patients with positive HBsAg were characterized by quantitatively measuring HBsAg and HBV DNA, sequencing large S genes, and observing clinical features. Compared with common hepatitis B patients, the patients with coexisting HBsAg and anti-HBs had lower HBsAg and HBV DNA levels. These two groups had similar rate of pre-S deletion mutations. However, in patients with coexisting HBsAg and anti-HBs, more amino acid substitutions in the a determinant of S gene were observed in HBV genotype C, but not in genotype B. Fourteen patients with coexisting HBsAg and anti-HBs were followed up for an average of 15.5 months. There were no significant changes in the levels of HBsAg, anti-HBs, HBV DNA and ALT over the follow-up period. Compared with the baseline sequences, amino acid substitutions in the MHR of HBsAg occurred in 14.3% (2/14) patients. In conclusion, coexistence of HBsAg and anti-HBs may be associated with higher frequency of mutations in the a determinant of HBV genotype C.

Development of candidate combination vaccine for hepatitis E and hepatitis B: a liposome encapsulation approach.

PubMed

Shrivastava, Shubham; Lole, Kavita S; Tripathy, Anuradha S; Shaligram, Umesh S; Arankalle, Vidya A

2009-11-05

To reduce extra injections, cost and ensure better coverage, use of combination vaccines is preferable. An attempt was made to evaluate the encapsulation of hepatitis E virus neutralizing epitope (NE) region and hepatitis B virus surface antigen (HBsAg) in liposomes as DNAs, proteins and DNA+protein. Mice groups were immunized with different liposome-encapsulated formulations and monitored for anti-HEV and anti-HBs titres, IgG subtypes, antigen-specific lymphocyte proliferation and cytokine levels. The protective levels of anti-HBs and in vitro virus-binding capacity of anti-HEV antibodies were assessed. Liposome-encapsulated DNA either singly or in combination did not elicit antibody response. Anti-HEV and anti-HBs IgG titres of individual component of protein alone (Lipo-E-P/Lipo-B-P) or DNA+protein formulations (Lipo-E-DP/Lipo-B-DP) were comparable to respective titres in combination vaccine of protein (Lipo-BE-P) and DNA+protein formulations (Lipo-BE-DP). IgG1 levels were significantly higher in Lipo-BE-P group whereas, equivalent levels of IgG1 and IgG2a were observed in Lipo-BE-DP group against both components of the vaccine. Combination vaccine group showed mixed Th1/Th2 cytokine profile. Liposome entrapped NE and HBsAg in protein and DNA+protein formats induce excellent immune response to both the components and need to be evaluated in higher animals.

10 year assessment of infant hepatitis B vaccination program, in the Loyalty Islands (New Caledonia).

PubMed

Berlioz-Arthaud, Alain; Perolat, Philippe; Buisson, Yves

2003-06-20

To evaluate the decrease of hepatitis B prevalence in New Caledonia 10 years after the implementation of a neonatal vaccination program and discuss the need of any booster in preadolescents. A survey was conducted in the Loyalty Islands, involving 593 children aged 8-11 years. Serological profiles were determined using three parameters: antibodies to core and surface antigens and HBs Ag. The vaccine coverage rate is 93 and 89% of the children are protected against hepatitis B. However, 8% of them did have contact with the virus and 1.3% are carriers. Thirty-eight percent of the vaccinated children had their first injection later than the age of 3 months. This study attests that the neonatal immunisation is accepted and followed. The prevalence reduction is not as great as expected, probably due to excess delay in primary vaccination. Hepatitis B eradication could be achieved in New Caledonia by starting immunisation at birth, and by implementing a global catch-up program among preadolescents.

IgA response and protection following nasal vaccination of chickens with Newcastle disease virus DNA vaccine nanoencapsulated with Ag@SiO2 hollow nanoparticles

PubMed Central

Zhao, Kai; Rong, Guangyu; Hao, Yan; Yu, Lu; Kang, Hong; Wang, Xin; Wang, Xiaohua; Jin, Zheng; Ren, Zhiyu; Li, Zejun

2016-01-01

Newcastle disease caused by ND virus (NDV) is a highly contagious disease of birds. Vaccine for effective protection of poultry animals from NDV infection is urgently needed. Mucosal immunity plays a very important role in the antiviral immune response. In this study, a NDV F gene-containing DNA vaccine encapsulated in Ag@SiO2 hollow nanoparticles (pFDNA-Ag@SiO2-NPs) with an average diameter of 500 nm were prepared to assess the mucosal immune response. These nanoparticles exhibited low cytotoxicity and did not destroy the bioactivity of plasmid DNA, which could be expressed in vitro. The plasmid DNA was sustainably released after an initial burst release. In vivo immunization showed that the intranasal immunization of chickens with pFDNA-Ag@SiO2-NPs induced high titers of serum antibody, significantly promoted lymphocyte proliferation and induced higher expression levels of IL-2 and IFN-γ in a dose-dependent manner. These results indicated that the Ag@SiO2 hollow nanoparticles could serve as an efficient and safe delivery carrier for NDV DNA vaccine to induce mucosal immunity. This study has provided promising results for the further development of mucosal vaccines encapsulated in inorganic nanoparticles. PMID:27170532

IgA response and protection following nasal vaccination of chickens with Newcastle disease virus DNA vaccine nanoencapsulated with Ag@SiO2 hollow nanoparticles

NASA Astrophysics Data System (ADS)

Zhao, Kai; Rong, Guangyu; Hao, Yan; Yu, Lu; Kang, Hong; Wang, Xin; Wang, Xiaohua; Jin, Zheng; Ren, Zhiyu; Li, Zejun

2016-05-01

Newcastle disease caused by ND virus (NDV) is a highly contagious disease of birds. Vaccine for effective protection of poultry animals from NDV infection is urgently needed. Mucosal immunity plays a very important role in the antiviral immune response. In this study, a NDV F gene-containing DNA vaccine encapsulated in Ag@SiO2 hollow nanoparticles (pFDNA-Ag@SiO2-NPs) with an average diameter of 500 nm were prepared to assess the mucosal immune response. These nanoparticles exhibited low cytotoxicity and did not destroy the bioactivity of plasmid DNA, which could be expressed in vitro. The plasmid DNA was sustainably released after an initial burst release. In vivo immunization showed that the intranasal immunization of chickens with pFDNA-Ag@SiO2-NPs induced high titers of serum antibody, significantly promoted lymphocyte proliferation and induced higher expression levels of IL-2 and IFN-γ in a dose-dependent manner. These results indicated that the Ag@SiO2 hollow nanoparticles could serve as an efficient and safe delivery carrier for NDV DNA vaccine to induce mucosal immunity. This study has provided promising results for the further development of mucosal vaccines encapsulated in inorganic nanoparticles.

Functional Analysis of the α-1,3-Glucan Synthase Genes agsA and agsB in Aspergillus nidulans: AgsB Is the Major α-1,3-Glucan Synthase in This Fungus

PubMed Central

Yoshimi, Akira; Sano, Motoaki; Inaba, Azusa; Kokubun, Yuko; Fujioka, Tomonori; Mizutani, Osamu; Hagiwara, Daisuke; Fujikawa, Takashi; Nishimura, Marie; Yano, Shigekazu; Kasahara, Shin; Shimizu, Kiminori; Yamaguchi, Masashi; Kawakami, Kazuyoshi; Abe, Keietsu

2013-01-01

Although α-1,3-glucan is one of the major cell wall polysaccharides in filamentous fungi, the physiological roles of α-1,3-glucan remain unclear. The model fungus Aspergillus nidulans possesses two α-1,3-glucan synthase (AGS) genes, agsA and agsB. For functional analysis of these genes, we constructed several mutant strains in A. nidulans: agsA disruption, agsB disruption, and double-disruption strains. We also constructed several CagsB strains in which agsB expression was controlled by the inducible alcA promoter, with or without the agsA-disrupting mutation. The agsA disruption strains did not show markedly different phenotypes from those of the wild-type strain. The agsB disruption strains formed dispersed hyphal cells under liquid culture conditions, regardless of the agsA genetic background. Dispersed hyphal cells were also observed in liquid culture of the CagsB strains when agsB expression was repressed, whereas these strains grew normally in plate culture even under the agsB-repressed conditions. Fractionation of the cell wall based on the alkali solubility of its components, quantification of sugars, and 13C-NMR spectroscopic analysis revealed that α-1,3-glucan was the main component of the alkali-soluble fraction in the wild-type and agsA disruption strains, but almost no α-1,3-glucan was found in the alkali-soluble fraction derived from either the agsB disruption strain or the CagsB strain under the agsB-repressed conditions, regardless of the agsA genetic background. Taken together, our data demonstrate that the two AGS genes are dispensable in A. nidulans, but that AgsB is required for normal growth characteristics under liquid culture conditions and is the major AGS in this species. PMID:23365684

rBCG30-Induced Immunity and Cross-Protection against Mycobacterium leprae Challenge Are Enhanced by Boosting with the Mycobacterium tuberculosis 30-Kilodalton Antigen 85B

PubMed Central

Gillis, Thomas P.; Tullius, Michael V.

2014-01-01

Leprosy remains a major global health problem and typically occurs in regions in which tuberculosis is endemic. Vaccines are needed that protect against both infections and do so better than the suboptimal Mycobacterium bovis BCG vaccine. Here, we evaluated rBCG30, a vaccine previously demonstrated to induce protection superior to that of BCG against Mycobacterium tuberculosis and Mycobacterium bovis challenge in animal models, for efficacy against Mycobacterium leprae challenge in a murine model of leprosy. rBCG30 overexpresses the M. tuberculosis 30-kDa major secretory protein antigen 85B, which is 85% homologous with the M. leprae homolog (r30ML). Mice were sham immunized or immunized intradermally with BCG or rBCG30 and challenged 2.5 months later by injection of viable M. leprae into each hind footpad. After 7 months, vaccine efficacy was assessed by enumerating the M. leprae bacteria per footpad. Both BCG and rBCG30 induced significant protection against M. leprae challenge. In the one experiment in which a comparison between BCG and rBCG30 was feasible, rBCG30 induced significantly greater protection than did BCG. Immunization of mice with purified M. tuberculosis or M. leprae antigen 85B also induced protection against M. leprae challenge but less so than BCG or rBCG30. Notably, boosting rBCG30 with M. tuberculosis antigen 85B significantly enhanced r30ML-specific immune responses, substantially more so than boosting BCG, and significantly augmented protection against M. leprae challenge. Thus, rBCG30, a vaccine that induces improved protection against M. tuberculosis, induces cross-protection against M. leprae that is comparable or potentially superior to that induced by BCG, and boosting rBCG30 with antigen 85B further enhances immune responses and protective efficacy. PMID:25001602

rBCG30-induced immunity and cross-protection against Mycobacterium leprae challenge are enhanced by boosting with the Mycobacterium tuberculosis 30-kilodalton antigen 85B.

PubMed

Gillis, Thomas P; Tullius, Michael V; Horwitz, Marcus A

2014-09-01

Leprosy remains a major global health problem and typically occurs in regions in which tuberculosis is endemic. Vaccines are needed that protect against both infections and do so better than the suboptimal Mycobacterium bovis BCG vaccine. Here, we evaluated rBCG30, a vaccine previously demonstrated to induce protection superior to that of BCG against Mycobacterium tuberculosis and Mycobacterium bovis challenge in animal models, for efficacy against Mycobacterium leprae challenge in a murine model of leprosy. rBCG30 overexpresses the M. tuberculosis 30-kDa major secretory protein antigen 85B, which is 85% homologous with the M. leprae homolog (r30ML). Mice were sham immunized or immunized intradermally with BCG or rBCG30 and challenged 2.5 months later by injection of viable M. leprae into each hind footpad. After 7 months, vaccine efficacy was assessed by enumerating the M. leprae bacteria per footpad. Both BCG and rBCG30 induced significant protection against M. leprae challenge. In the one experiment in which a comparison between BCG and rBCG30 was feasible, rBCG30 induced significantly greater protection than did BCG. Immunization of mice with purified M. tuberculosis or M. leprae antigen 85B also induced protection against M. leprae challenge but less so than BCG or rBCG30. Notably, boosting rBCG30 with M. tuberculosis antigen 85B significantly enhanced r30ML-specific immune responses, substantially more so than boosting BCG, and significantly augmented protection against M. leprae challenge. Thus, rBCG30, a vaccine that induces improved protection against M. tuberculosis, induces cross-protection against M. leprae that is comparable or potentially superior to that induced by BCG, and boosting rBCG30 with antigen 85B further enhances immune responses and protective efficacy. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Vaccination against group B streptococcus.

PubMed

Heath, Paul T; Feldman, Robert G

2005-04-01

Streptococcus agalactiae (Group B streptococcus) is an important cause of disease in infants, pregnant women, the elderly and in immunosuppressed adults. An effective vaccine is likely to prevent the majority of infant disease (both early and late onset), as well as Group B streptococcus-related stillbirths and prematurity, to avoid the current real and theoretical limitations of intrapartum antibiotic prophylaxis, and to be cost effective. The optimal time to administer such a vaccine would be in the third trimester of pregnancy. The main limitations on the production of a Group B streptococcus vaccine are not technical or scientific, but regulatory and legal. A number of candidates including capsular conjugate vaccines using traditional carrier proteins such as tetanus toxoid and mutant diphtheria toxin CRM197, as well as Group B streptococcus-specific proteins such as C5a peptidase, protein vaccines using one or more Group B streptococcus surface proteins and mucosal vaccines, have the potential to be successful vaccines. The capsular conjugate vaccines using tetanus and CRM197 carrier proteins are the most advanced candidates, having already completed Phase II human studies including use in the target population of pregnant women (tetanus toxoid conjugate), however, no definitive protein conjugates have yet been trialed. However, unless the regulatory environment is changed specifically to allow the development of a Group B streptococcus vaccine, it is unlikely that one will ever reach the market.

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

Intradermal vaccination of adults with three low doses (2 micrograms) of recombinant hepatitis B vaccine. II. Persistence of immunity and induction of immunologic memory.

PubMed

Elisbão, Maria do Carmo M; Baldy, José Luís da S; Bonametti, Ana Maria; Reiche, Edna Maria V; Morimoto, Helena K; Pontello, Rubens; Matsuo, Tiemi; Ferelle, Antônio; Neves, Jayme

2003-12-01

Of the 110 dentists who had presented seroconversion 50 days after the intradermal application of three 2 micrograms doses of the Belgian recombinant vaccine against hepatitis B (HB), administered eight years before at an interval of one month between the 1st and 2nd doses and of five months between the 2nd and 3rd doses, 51 were included for the assessment of the persistence of immunity. None of the dentists had hepatitis or had received HB vaccine during this period. All subjects were submitted to serological tests for the detection of the following markers of hepatitis B virus (HBV) infection: HBsAg, anti-HBc, HBeAg, anti-HBe, and anti-HBs, with no HBsAg, anti-HBc, HBeAg or anti-HBe being detected. A microparticle enzyme immunoassay (MEIA) revealed the presence of anti-HBs at protective titers (> or = 10 mIU/ml) in 42 dentists (82.4%), with the anti-HBs titer being higher than 100 mIU/ml in 36 of them (70.6%) (good responders), between 10 and 100 mIU/ml in 6 (11.8%) (poor responders), and lower than 10 mIU/ml in 9 (17.6%) (non-responders). According to clinical data and serological tests, none of the dentists had presented disease or latent HBV infection during the eight years following the first vaccination. A 2 micrograms booster dose was administered intradermally to eight dentists with anti-HBs titers lower than 10 mIU/ml (non-responders) and to six dentists with titers ranging from 10 to 100 mIU/ml (poor responders); the determination of anti-HBs one month later demonstrated the occurrence of seroconversion in the eight non-responders and an increase in anti-HBs titer in the six poor responders. In summary, the present results demonstrated the prolonged persistence of protection against HBV infection and the development of immunologic memory provided by vaccination against HB--with intradermal application of three 2 micrograms doses of the Belgian recombinant vaccine at 0, 1, and 6 months--carried out eight years before in 51 dentists.

Efficacy and effectiveness of infant vaccination against chronic hepatitis B in the Gambia Hepatitis Intervention Study (1986-90) and in the nationwide immunisation program.

PubMed

Peto, Thomas J; Mendy, Maimuma E; Lowe, Yamundow; Webb, Emily L; Whittle, Hilton C; Hall, Andrew J

2014-01-07

Gambian infants were not routinely vaccinated against hepatitis B virus (HBV) before 1986. During 1986-90 the Gambia Hepatitis Intervention Study (GHIS) allocated 125,000 infants, by area, to vaccination or not and thereafter all infants were offered the vaccine through the nationwide immunisation programme. We report HBV serology from samples of GHIS vaccinees and unvaccinated controls, and from children born later. During 2007-08, 2670 young adults born during the GHIS (1986-90) were recruited from 80 randomly selected villages and four townships. Only 28% (753/2670) could be definitively linked to their infant HBV vaccination records (255 fully vaccinated, 23 partially vaccinated [1-2 doses], 475 not vaccinated). All were tested for current HBV infection (HBV surface antigen [HBsAg]) and, if HBsAg-negative, evidence of past infection (HBV core-protein antibody [anti-HBc]). HBsAg-positive samples (each with two age- and sex-matched HBsAg-negative samples) underwent liver function tests. In addition, 4613 children born since nationwide vaccination (in 1990-2007) were tested for HBsAg. Statistical analyses ignore clustering. Comparing fully vaccinated vs unvaccinated GHIS participants, current HBV infection was 0.8% (2/255) vs 12.4% (59/475), p < 0.0001, suggesting 94% (95% CI 77-99%) vaccine efficacy. Among unvaccinated individuals, the prevalence was higher in males (p = 0.015) and in rural areas (p = 0.009), but adjustment for this did not affect estimated vaccine efficacy. Comparing fully vaccinated vs unvaccinated participants, anti-HBc was 27.4% (70/255) vs 56.0% (267/475), p < 0.00001. Chronic active hepatitis was not common: the proportion of HBsAg-positive subjects with abnormal liver function tests (ALT > 2 ULN) was 4.1%, compared with 0.2% in those HBsAg-negative. The prevalence of antibodies to hepatitis C virus was low (0.5%, 13/2592). In children born after the end of GHIS, HBsAg prevalence has remained low; 1.4% (15/1103) in those born between 1990

An improved Abbott ARCHITECT assay for the detection of hepatitis B virus surface antigen (HBsAg).

PubMed

Lou, Sheng C; Pearce, Sandra K; Lukaszewska, Teresa X; Taylor, Russell E; Williams, Gregg T; Leary, Thomas P

2011-05-01

The sensitive and accurate detection of hepatitis B virus surface antigen (HBsAg) is critical to the identification of infection and the prevention of transfusion transmitted disease. Improvement in HBsAg assay sensitivity is essential to reduce the window to detect an acute HBV infection. Additionally, the sensitive detection of HBsAg mutants that continue to evolve due to vaccine escape, immune selection and an error prone reverse transcriptase is a necessity. A fully automated HBsAg prototype assay on the Abbott ARCHITECT instrument was developed to improve sensitivity and mutant detection. This magnetic microparticle-based assay utilizes anti-HBsAg monoclonal antibodies to capture antigen present in serum or plasma. Captured antigen is then detected using anti-HBsAg antibody conjugated with the chemiluminescent compound, acridinium. The sensitivity of the ARCHITECT HBsAg prototype assay was improved as compared to the current ARCHITECT, PRISM, and competitor HBsAg assays. The enhancement in assay sensitivity was demonstrated by the use of commercially available HBV seroconversion panels. The prototype assay detected more panel members (185 of 383) vs. the current ARCHITECT (171), PRISM (181), or competitor HBsAg assays (73/140 vs. 62/140, respectively). The ARCHITECT prototype assay also efficiently detected all mutants evaluated. Finally, the sensitivity improvement did not compromise the specificity of the assay (99.94%). An improved Abbott ARCHITECT HBsAg prototype assay with enhanced detection of HBsAg and HBsAg mutants, as well as equivalent specificity was developed for the detection, diagnosis, and management of HBV infection. Copyright © 2011 Elsevier B.V. All rights reserved.

Pre-vaccination inflammation and B-cell signalling predict age-related hyporesponse to hepatitis B vaccination

PubMed Central

Fourati, Slim; Cristescu, Razvan; Loboda, Andrey; Talla, Aarthi; Filali, Ali; Railkar, Radha; Schaeffer, Andrea K.; Favre, David; Gagnon, Dominic; Peretz, Yoav; Wang, I-Ming; Beals, Chan R.; Casimiro, Danilo R.; Carayannopoulos, Leonidas N.; Sékaly, Rafick-Pierre

2016-01-01

Aging is associated with hyporesponse to vaccination, whose mechanisms remain unclear. In this study hepatitis B virus (HBV)-naive older adults received three vaccines, including one against HBV. Here we show, using transcriptional and cytometric profiling of whole blood collected before vaccination, that heightened expression of genes that augment B-cell responses and higher memory B-cell frequencies correlate with stronger responses to HBV vaccine. In contrast, higher levels of inflammatory response transcripts and increased frequencies of pro-inflammatory innate cells correlate with weaker responses to this vaccine. Increased numbers of erythrocytes and the haem-induced response also correlate with poor response to the HBV vaccine. A transcriptomics-based pre-vaccination predictor of response to HBV vaccine is built and validated in distinct sets of older adults. This moderately accurate (area under the curve≈65%) but robust signature is supported by flow cytometry and cytokine profiling. This study is the first that identifies baseline predictors and mechanisms of response to the HBV vaccine. PMID:26742691

Hepatitis B and C status among health care workers in the five main hospitals in eastern Libya.

PubMed

Elzouki, Abdel-Nasser; Elgamay, Salwa M; Zorgani, Abdeulaziz; Elahmer, Omer

2014-01-01

The aim of the present study was to determine the frequency of hepatitis B and C transmission to health care workers (HCWs) in five major hospitals in eastern Libya and to analyze how the risk of these infections are affected by the type of occupation, hospital work place and working period. From July 2008 to June 2009, 601 HCWs (mean age: 32.90 ± 8.85 years) were tested for HBV and HCV markers using ELISA techniques. Polymerase chain reaction (PCR) was performed on all positive samples of HBsAg and Anti-HCV antibody to determine the level of HBV-DNA and HCV-RNA viremia, respectively. The overall frequency of HBsAg positivity was 1.8%. Anti-HBc, HBeAg and Anti-HBe antibodies were found in 8.5%, 0.7% and 8.0% of samples, respectively. The HBV-DNA level was positive in 55% of all HBsAg-positive samples. Approximately half of the HCWs (51.4%) were Anti-HBs antibody positive. The overall positivity rate of Anti-HCV antibodies was 2.0%, and HCV-RNA was positive in 33.3% of these samples. Overall, 52% of HCWs reported receiving full vaccination doses (three doses) against HBV infection. Among them, anti-HBs positivity was approximately 98.0%. 3.9% of those who never received any HBV vaccination dose were HBsAg positive, compared to 1.3% HBsAg positive in those HCWs who had received one or two doses of hepatitis B vaccine (p=0.01 for all comparisons). Nurses and nurse-aides had the highest rates of both HBsAg and Anti-HCV among the studied HCWs (HBsAg: 2.1% and 3.2%; Anti-HCV: 3.2% and 4.9%, respectively). It is noteworthy that doctors also had a relatively high prevalence rate of Anti-HCV (2.2%). Obstetric wards, isolation room, dialysis units and dentist work places had higher frequencies of HBV. HCV was found to be higher in the medical and surgical wards (the prevalence varied between 3% and 5.6%). There was no significant difference between HBsAg status and the work period of HCWs. In conclusion, universal precautions should be applied for the care of all patients

Effects of vaccine-acquired polyclonal anti-HBs antibodies on the prevention of HBV infection of non-vaccine genotypes.

PubMed

Kato, Masaki; Hamada-Tsutsumi, Susumu; Okuse, Chiaki; Sakai, Aiko; Matsumoto, Nobuyuki; Sato, Masaaki; Sato, Toshiyuki; Arito, Mitsumi; Omoteyama, Kazuki; Suematsu, Naoya; Okamoto, Kazuki; Kato, Takanobu; Itoh, Fumio; Sumazaki, Ryo; Tanaka, Yasuhito; Yotsuyanagi, Hiroshi; Kato, Tomohiro; Kurokawa, Manae Suzuki

2017-09-01

In universal hepatitis B (HB) vaccination, single vaccine-derived polyclonal anti-HBs antibodies (anti-HBs) need to inhibit infection of HB viruses (HBV) of non-vaccine genotypes. We experimentally addressed this issue. Anti-HBs-positive sera were obtained by vaccination with genotype A- or C-derived HBs antigen (HBsAg, gtA-sera or gtC-sera). Their reactivity to genotype A- and C-derived HBsAg (gtA-Ag and gtC-Ag) was measured by ELISA. The capacity of sera to neutralize HBV was evaluated using an in vitro infection model. Of 135 anti-gtA-Ag-reactive gtA-sera, 134 (99.3%) were anti-gtC-Ag-reactive. All (100%) 120 anti-gtC-Ag-reactive gtC-sera were anti-gtA-Ag-reactive. The reactivity to gtA-Ag was strongly correlated with that to gtC-Ag (gtA-sera, ρ = 0.989; gtC-sera, ρ = 0.953; p < 0.01). In gtA-sera (n = 10), anti-HBs to gtA-Ag were less completely absorbed with gtC-Ag (96.4%) than with gtA-Ag (100%, p < 0.05). Similarly, in gtC-sera (n = 10), anti-HBs to gtC-Ag were less completely absorbed with gtA-Ag (96.0%) than with gtC-Ag (100%, p < 0.01). Thus, 3.6 and 4.0% of anti-HBs in gtA-sera and gtC-sera were vaccine genotype HBsAg-specific, respectively. In the neutralization test, gtA-sera (n = 4) and gtC-sera (n = 3) with anti-HBs titers adjusted to 100 mIU/mL equally inhibited genotype C HBV infection (92.8 vs. 95.4%, p = 0.44). However, at 30 mIU/mL, the gtA-sera less effectively inhibited infection than the gtC-sera (60.2 vs. 90.2%, p < 0.05). Vaccination with genotype A- or C-derived HBsAg provided polyclonal anti-HBs that sufficiently bound to non-vaccine genotype HBsAg. However, a small portion of anti-HBs were specific to the vaccine genotype HBsAg. High anti-HBs titers would be required to prevent HBV infection of non-vaccine genotypes. UMIN/CTR UMIN000014363.

[Anti-hepatitis B surface antigen titres in vaccinated dentistry students at Damascus University].

PubMed

Srour, I H; Mashlah, A

2012-06-01

Dental practice carries considerable danger for acquiring bloodborne pathogens such as hepatitis B virus (HBV). Vaccination against this virus is an important approach to reducing the infection. Post-vaccination test to confirm the seroconversion is important also. Over the period 1 March-31 May 2010, we assessed the efficacy of HBV vaccination among 91 fourth-year dental students at Damascus University, who were vaccinated under the mandatory Faculty of Dentistry programme. Anti-HBsAg antibody titres were determined in the blood samples using an enzyme immunoassay to measure; > or = 10 IU/mm was considered an adequate response titer. Seven of the 91 dentistry students (7.7%) had anti-HBs antibody titre < 10 mlU/mL. The frequency of unresponsiveness was significantly higherwith smoking (P = 0.012) and alcohol consumption (P = 0.014). Anti-HBs test should be included in routine immunization services of the School of Dentistry at Damascus University.

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

A window of opportunity: declining rates of hepatitis B virus infection among injection drug users in Rio de Janeiro, and prospects for targeted hepatitis B vaccination.

PubMed

Oliveira, Sabrina A N; Hacker, Mariana A; Oliveira, M Lourdes A; Yoshida, Clara F T; Telles, Paulo R; Bastos, Francisco I

2005-01-01

To measure hepatitis B virus (HBV) infection rates among injection drug users in Rio de Janeiro, Brazil, and to report their knowledge of and attitudes toward hepatitis and HBV vaccination. 609 injection drug users recruited in Rio de Janeiro between 1999 and 2001 answered a questionnaire and were tested for hepatitis B and other blood-borne infections. Questions covered sociodemographic information, alcohol and illicit drug consumption, drug injection and sexual practices, medical history, and knowledge about HIV, AIDS and viral hepatitis. The prevalence of HBV infection was 27.1%, with 3.4% of the sample positive for HbsAg (active infection) and 0.8% positive for anti-HBs (indicating previous HBV vaccination). Most interviewees (81.3%) were aware of at least one form of viral hepatitis and received information from many different sources. In agreement with laboratory findings, 96.7% of the interviewees stated they had never been vaccinated against hepatitis B, but almost all unvaccinated interviewees (97.8%) said they would volunteer to be vaccinated if HBV vaccination were available. Few of the injection drug users surveyed had ever been vaccinated against HBV. Although most were aware of the risks posed by viral hepatitis, this awareness seldom translated into consistent behavioral change. The participants' willingness to be vaccinated against HBV suggests that the implementation of vaccination for this population may help decrease rates of hepatitis B infection.

Serodiagnostic potential of immuno-PCR using a cocktail of mycobacterial antigen 85B, ESAT-6 and cord factor in tuberculosis patients.

PubMed

Singh, Netrapal; Sreenivas, Vishnubhatla; Sheoran, Abhishek; Sharma, Suman; Gupta, Krishna B; Khuller, Gopal K; Mehta, Promod K

2016-01-01

A novel indirect immuno-polymerase chain reaction (I-PCR) assay was developed for the detection of circulating anti-Ag85B (antigen 85B, Rv1886c), anti-ESAT-6 (early secretory antigenic target-6, Rv3875) and anti-cord factor (trehalose 6,6'-dimycolate) antibodies from the sera samples of pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) patients and the results were compared with an analogous enzyme-linked immunosorbent assay (ELISA). We covalently attached the amino-modified reporter DNA to the dithiothreitol (DTT)-reduced anti-human IgG antibody through a chemical linker succinimidyl 4-[N-maleimidomethyl]-cyclohexane-1-carboxylate (SMCC). The detection of cocktail of anti-Ag85B, anti-ESAT-6 and anti-cord factor antibodies was found to be superior to the detection of individual antibodies. The sensitivities of 89.5% and 77.5% with I-PCR and 70.8% and 65% with ELISA were observed in smear-positive and smear-negative PTB cases, respectively with high specificity (90.9%). On the other hand, a sensitivity of 77.5% with I-PCR and 65% with ELISA was observed in EBTB cases. The detection of cocktail of antibodies by I-PCR is likely to improve the utility of existing algorithms for TB diagnosis. Copyright © 2015 Elsevier B.V. All rights reserved.

Experience with hepatitis A and B vaccines.

PubMed

Davis, Jeffrey P

2005-10-01

The lengthy history of efforts to understand the pathogenesis and means of preventing and controlling both hepatitis A and B is noteworthy for many exceptional scientific achievements. Among these are the development of vaccines to prevent the spread of infection through induction of active immunity to hepatitis A virus (HAV) and hepatitis B virus (HBV). The first plasma-derived hepatitis B vaccine was licensed in the United States in 1981 and was replaced by recombinant hepatitis B vaccines in 1986 and 1989. Vaccines to prevent HAV infection were licensed in the United States in 1995 and 1996. Subsequently, combination vaccines that included both hepatitis A and B vaccine components, or the hepatitis B component in combination with other commonly administered vaccines, were licensed in the United States. Despite significant reductions in hepatitis-related morbidity and mortality that have resulted from widespread use of these vaccines, vaccine-preventable morbidity and mortality still occur. The purposes of this article are to review clinical trial and other experience with hepatitis A and B vaccines in healthy individuals as well as in those with chronic liver disease, infected with the human immunodeficiency virus, or requiring hemodialysis; describe the impact that these vaccines and national recommendations for vaccination have had on reducing the incidence of HAV and HBV infection; and recommend expansion of these recommendations to include universal vaccination of adults as a means of further reducing the burden of viral hepatitis.

A decision analytic model for prevention of hepatitis B virus infection in Sub-Saharan Africa using birth-dose vaccination.

PubMed

Anderson, Sarah; Harper, Lorie M; Dionne-Odom, Jodie; Halle-Ekane, Gregory; Tita, Alan T N

2018-04-01

To compare prenatal maternal hepatitis B virus (HBV) screening and infant vaccination strategies to inform policy on HBV prevention in Sub-Saharan Africa. A decision analytic model was created using previously published data to assess the ability of three intervention strategies to prevent HBV infection by age 10 years. Strategy 1 comprised of universal vaccination with a pentavalent vaccine (HBV, diphtheria, tetanus, pertussis, and Haemophilus influenzae) at age 6 weeks. Strategy 2 comprised of universal HBV vaccine at birth plus pentavalent vaccine. Strategy 3 comprised of maternal prenatal HBV screening and targeted HBV vaccine at birth for all exposed infants plus pentavalent vaccine. The reference strategy provided neither maternal screening nor infant vaccination. Rates of HBV infection and costs were compared. The reference strategy had an HBV infection rate of 2360 per 10 000 children. The HBV infection rate for strategy 1 was 813 per 10 000 children vaccinated (1547 cases prevented). Strategies 2 and 3 prevented an additional 384 cases and 362 cases, respectively. Inclusion of HBV vaccination at birth was the preferred approach at a willingness-to-pay threshold of US$150. Including a birth-dose HBV vaccine in the standard schedule was both cost-effective and prevented additional infections. © 2018 International Federation of Gynecology and Obstetrics.

Antigen 85C Inhibition Restricts Mycobacterium tuberculosis Growth through Disruption of Cord Factor Biosynthesis

PubMed Central

Warrier, Thulasi; Tropis, Marielle; Werngren, Jim; Diehl, Anne; Gengenbacher, Martin; Schlegel, Brigitte; Schade, Markus; Oschkinat, Hartmut; Daffe, Mamadou; Hoffner, Sven; Eddine, Ali Nasser

2012-01-01

The antigen 85 (Ag85) protein family, consisting of Ag85A, -B, and -C, is vital for Mycobacterium tuberculosis due to its role in cell envelope biogenesis. The mycoloyl transferase activity of these proteins generates trehalose dimycolate (TDM), an envelope lipid essential for M. tuberculosis virulence, and cell wall arabinogalactan-linked mycolic acids. Inhibition of these enzymes through substrate analogs hinders growth of mycobacteria, but a link to mycolic acid synthesis has not been established. In this study, we characterized a novel inhibitor of Ag85C, 2-amino-6-propyl-4,5,6,7-tetrahydro-1-benzothiophene-3-carbonitrile (I3-AG85). I3-AG85 was isolated from a panel of four inhibitors that exhibited structure- and dose-dependent inhibition of M. tuberculosis division in broth culture. I3-AG85 also inhibited M. tuberculosis survival in infected primary macrophages. Importantly, it displayed an identical MIC against the drug-susceptible H37Rv reference strain and a panel of extensively drug-resistant/multidrug-resistant M. tuberculosis strains. Nuclear magnetic resonance analysis indicated binding of I3-AG85 to Ag85C, similar to its binding to the artificial substrate octylthioglucoside. Quantification of mycolic acid-linked lipids of the M. tuberculosis envelope showed a specific blockade of TDM synthesis. This was accompanied by accumulation of trehalose monomycolate, while the overall mycolic acid abundance remained unchanged. Inhibition of Ag85C activity also disrupted the integrity of the M. tuberculosis envelope. I3-AG85 inhibited the division of and reduced TDM synthesis in an M. tuberculosis strain deficient in Ag85C. Our results indicate that Ag85 proteins are promising targets for novel antimycobacterial drug design. PMID:22290959

Viral booster vaccines improve Mycobacterium bovis BCG-induced protection against bovine tuberculosis.

PubMed

Vordermeier, H Martin; Villarreal-Ramos, Bernardo; Cockle, Paul J; McAulay, Martin; Rhodes, Shelley G; Thacker, Tyler; Gilbert, Sarah C; McShane, Helen; Hill, Adrian V S; Xing, Zhou; Hewinson, R Glyn

2009-08-01

Previous work with small-animal laboratory models of tuberculosis has shown that vaccination strategies based on heterologous prime-boost protocols using Mycobacterium bovis bacillus Calmette-Guérin (BCG) to prime and modified vaccinia virus Ankara strain (MVA85A) or recombinant attenuated adenoviruses (Ad85A) expressing the mycobacterial antigen Ag85A to boost may increase the protective efficacy of BCG. Here we report the first efficacy data on using these vaccines in cattle, a natural target species of tuberculous infection. Protection was determined by measuring development of disease as an end point after M. bovis challenge. Either Ad85A or MVA85A boosting resulted in protection superior to that given by BCG alone: boosting BCG with MVA85A or Ad85A induced significant reduction in pathology in four/eight parameters assessed, while BCG vaccination alone did so in only one parameter studied. Protection was particularly evident in the lungs of vaccinated animals (median lung scores for naïve and BCG-, BCG/MVA85A-, and BCG/Ad85A-vaccinated animals were 10.5, 5, 2.5, and 0, respectively). The bacterial loads in lymph node tissues were also reduced after viral boosting of BCG-vaccinated calves compared to those in BCG-only-vaccinated animals. Analysis of vaccine-induced immunity identified memory responses measured by cultured enzyme-linked immunospot assay as well as in vitro interleukin-17 production as predictors of vaccination success, as both responses, measured before challenge, correlated positively with the degree of protection. Therefore, this study provides evidence of improved protection against tuberculosis by viral booster vaccination in a natural target species and has prioritized potential correlates of vaccine efficacy for further evaluation. These findings also have implications for human tuberculosis vaccine development.

Effect of HBIG combined with hepatitis B vaccine on blocking HBV transmission between mother and infant and its effect on immune cells.

PubMed

Gong, Junling; Liu, Xing

2018-01-01

The effect of hepatitis B immune globulin (HBIG) combined with hepatitis B vaccine on blocking hepatitis B virus (HBV) transmission between mother and infant and its effect on immune cells were studied. Ninety newborn infants confirmed to be HBV surface antigen (HBsAg)-positive were divided equally into three groups. Group A newborns received the hepatitis B vaccine at 0, 1 and 6 months after birth (10 µg/time). Group B newborns received an intramuscular injection of 100 IU HBIG 2 h after birth before the same treatment as group A. Mothers of group C newborns received three gluteus maxinus injections of 200 IU HBIG. The newborns in group C got the same treatment as group B. The blocking effect of HBV transmission between mother and infant was evaluated, and cell immune function was assessed. There were significant differences in comparison of blocking success rates between group A and B, and between group A and C as well (p<0.05). At the end of 12 months follow-up, the CD4 + level and CD4 + /CD8 + ratio in group C were higher thanthose in group A and B (p<0.05). In addition, the level of CD8 + T lymphocyte in group C was lower than those in group A and B (p<0.05). In comparison of levels of CD4 + T lymphocyte at the end of 12 months follow-up and 24 h after birth, the differences were significant (p<0.05) in bothgroup B and C. The differences of IFN-γ levels betweengroups B/C and group A were significant (p<0.05). Forthose newborn infants born to mothers who were positivefor both HBsAg and HBeAg, HBIG intervention formothers during late pregnancy, together with combinedtreatment of HBIG and hepatitis B vaccine for infants, gavebetter blocking result of HBV transmission.

Hepatitis B vaccine booster dose: low-dose recombinant hepatitis B vaccines as a booster dose.

PubMed

Bryan, J P; MacArthy, P; Rudock, A; Fogarty, J P; Dowd, H; Legters, L J; Perine, P L

1997-06-01

The timing and best regimen for a booster dose of hepatitis B vaccine have not been determined. Two studies were conducted to determine the response to a booster dose of 5 micrograms recombinant hepatitis B vaccine. In the first study, a 5 micrograms (0.5 ml) dose of Recombivax HB was administered intramuscularly 38 months after the initial dose to 71 volunteers. In a second study, we offered a 5 micrograms dose recombinant hepatitis B vaccine, either Recombivax HB (0.5 ml) or Engerix B (0.25 ml), to students who had previously been immunized with three doses of vaccine. In the first study, among the 44 persons for whom postbooster sera were available, the geometric mean concentration of anti-hepatitis B surface antigens increased from 42 to 2090 mIU/ml after the 5 micrograms (0.5 ml) dose of Recombivax. In the second study, after a 5 micrograms (0.5 ml) dose of Recombivax, the geometric mean concentration increased from 43 to 990 mIU/ml (n = 48), and in the group that received a 5 micrograms (0.25 ml) dose of Engerix B, the concentration increased from 83 to 2337 mIU/ml (n = 45) (p = 0.18 for postdose concentrations). A 5 micrograms dose of recombinant vaccine results in an excellent booster response at a cost one fourth to one half that of a full 1 ml dose of vaccine.

Analysis of hepatitis B surface antigen (HBsAg) using high-sensitivity HBsAg assays in hepatitis B virus carriers in whom HBsAg seroclearance was confirmed by conventional assays.

PubMed

Ozeki, Itaru; Nakajima, Tomoaki; Suii, Hirokazu; Tatsumi, Ryoji; Yamaguchi, Masakatsu; Kimura, Mutsuumi; Arakawa, Tomohiro; Kuwata, Yasuaki; Ohmura, Takumi; Hige, Shuhei; Karino, Yoshiyasu; Toyota, Joji

2018-02-01

We investigated the utility of high-sensitivity hepatitis B surface antigen (HBsAg) assays compared with conventional HBsAg assays. Using serum samples from 114 hepatitis B virus (HBV) carriers in whom HBsAg seroclearance was confirmed by conventional HBsAg assays (cut-off value, 0.05 IU/mL), the amount of HBsAg was re-examined by high-sensitivity HBsAg assays (cut-off value, 0.005 IU/mL). Cases negative for HBsAg in both assays were defined as consistent cases, and cases positive for HBsAg in the high-sensitivity HBsAg assay only were defined as discrepant cases. There were 55 (48.2%) discrepant cases, and the range of HBsAg titers determined by high-sensitivity HBsAg assays was 0.005-0.056 IU/mL. Multivariate analysis showed that the presence of nucleos(t)ide analog therapy, liver cirrhosis, and negative anti-HBs contributed to the discrepancies between the two assays. Cumulative anti-HBs positivity rates among discrepant cases were 12.7%, 17.2%, 38.8%, and 43.9% at baseline, 1 year, 3 years, and 5 years, respectively, whereas the corresponding rates among consistent cases were 50.8%, 56.0%, 61.7%, and 68.0%, respectively. Hepatitis B virus DNA negativity rates were 56.4% and 81.4% at baseline, 51.3% and 83.3% at 1 year, and 36.8% and 95.7% at 3 years, among discrepant and consistent cases, respectively. Hepatitis B surface antigen reversion was observed only in discrepant cases. Re-examination by high-sensitivity HBsAg assays revealed that HBsAg was positive in approximately 50% of cases. Cumulative anti-HBs seroconversion rates and HBV-DNA seroclearance rates were lower in these cases, suggesting a population at risk for HBsAg reversion. © 2017 The Japan Society of Hepatology.

Safety and immunogenicity of a fully liquid vaccine containing five-component pertussis-diphtheria-tetanus-inactivated poliomyelitis-Haemophilus influenzae type b conjugate vaccines administered at two, four, six and 18 months of age

PubMed Central

Gold, Ronald; Barreto, Luis; Ferro, Santiago; Thippawong, John; Guasparini, Roland; Meekison, William; Russell, Margaret; Mills, Elaine; Harrison, Dana; Lavigne, Pierre

2007-01-01

OBJECTIVE The safety, immunogenicity and lot consistency of a fully liquid, five-component acellular pertussis combination vaccine, comprised of diphteria, tetanus and acellular pertussis, inactivated polio vaccine, Haemophilus influenzae type b (DTaP-IPV-Hib [Pediacel, sanofi pasteur, Canada]) were assessed and compared with that of Hib vaccine reconstituted with the five-component acellular pertussis combination vaccine (DTaP-IPV//Hib, Pentacel [sanofi pasteur, Canada]). METHODS Infants were recruited at vaccine study centres in Montreal, Quebec; Simon Fraser Health Region, British Columbia, and southern Alberta after the protocol had been approved by the relevant institutional ethics committees. Written informed consent was obtained from the parents or guardians of all subjects. At two months of age, the infants were randomly assigned to receive one of three consecutive production lots of DTaP-IPV-Hib by intramuscular injection. Reactions to vaccinations were assessed by parental observation and through telephone interviews conducted by study nurses. Blood samples were obtained at two, six, seven, 18 and 19 months of age for measurement of antibodies to vaccine antigens. RESULTS: Most injection site and systemic reactions were mild or moderate, and of brief duration. All infants were protected against tetanus, diphtheria and all three polio serotypes after both primary and booster vaccinations. Antibody responses to pertussis antigens were similar to those observed in Swedish infants, in whom the five-component vaccine was shown to be 85% effective. Proportions of infants with antipolyribosylribitol phosphate antibody of 0.15 μg/mL or greater and 1.0 μg/mL or greater, were 97.9% and 88.9%, respectively, following primary immunization, and 100% and 99% following booster vaccination. Safety and immunogenicity results with both reconstituted and fully liquid combination vaccines were comparable. CONCLUSIONS The fully liquid combination vaccine was comparable in

Progress in vaccination towards hepatitis B control and elimination in the Region of the Americas.

PubMed

Ropero Álvarez, Alba Maria; Pérez-Vilar, Silvia; Pacis-Tirso, Carmelita; Contreras, Marcela; El Omeiri, Nathalie; Ruiz-Matus, Cuauhtémoc; Velandia-González, Martha

2017-04-17

Over recent decades, the Region of the Americas has made significant progress towards hepatitis B elimination. We summarize the countries/territories' efforts in introducing and implementing hepatitis B (HB) vaccination and in evaluating its impact on HB virus seroprevalence. We collected information about HB vaccination schedules, coverage estimates, and year of vaccine introduction from countries/territories reporting to the Pan American Health Organization/World Health Organization (PAHO/WHO) through the WHO/UNICEF Joint Reporting Form on Immunization. We obtained additional information regarding countries/territories vaccination recommendations and strategies through communications with Expanded Program on Immunization (EPI) managers and national immunization survey reports. We identified vaccine impact studies conducted and published in the Americas. As of October 2016, all 51 countries/territories have included infant HB vaccination in their official immunization schedule. Twenty countries, whose populations represent over 90% of the Region's births, have included nationwide newborn HB vaccination. We estimated at 89% and 75%, the regional three-dose series and the birth dose HB vaccination coverage, respectively, for 2015. The impact evaluations of infant HB immunization programs in the Region have shown substantial reductions in HB surface antigen (HBsAg) seroprevalence. The achievements of vaccination programs in the Americas suggest that the elimination of perinatal and early childhood HB transmission could be feasible in the short-term. Moreover, the data gathered indicate that the Region may have already achieved the 2020 WHO goal for HB control.

Antigen Availability Shapes T Cell Differentiation and Function during Tuberculosis.

PubMed

Moguche, Albanus O; Musvosvi, Munyaradzi; Penn-Nicholson, Adam; Plumlee, Courtney R; Mearns, Helen; Geldenhuys, Hennie; Smit, Erica; Abrahams, Deborah; Rozot, Virginie; Dintwe, One; Hoff, Søren T; Kromann, Ingrid; Ruhwald, Morten; Bang, Peter; Larson, Ryan P; Shafiani, Shahin; Ma, Shuyi; Sherman, David R; Sette, Alessandro; Lindestam Arlehamn, Cecilia S; McKinney, Denise M; Maecker, Holden; Hanekom, Willem A; Hatherill, Mark; Andersen, Peter; Scriba, Thomas J; Urdahl, Kevin B

2017-06-14

CD4 T cells are critical for protective immunity against Mycobacterium tuberculosis (Mtb), the cause of tuberculosis (TB). Yet to date, TB vaccine candidates that boost antigen-specific CD4 T cells have conferred little or no protection. Here we examined CD4 T cell responses to two leading TB vaccine antigens, ESAT-6 and Ag85B, in Mtb-infected mice and in vaccinated humans with and without underlying Mtb infection. In both species, Mtb infection drove ESAT-6-specific T cells to be more differentiated than Ag85B-specific T cells. The ability of each T cell population to control Mtb in the lungs of mice was restricted for opposite reasons: Ag85B-specific T cells were limited by reduced antigen expression during persistent infection, whereas ESAT-6-specific T cells became functionally exhausted due to chronic antigenic stimulation. Our findings suggest that different vaccination strategies will be required to optimize protection mediated by T cells recognizing antigens expressed at distinct stages of Mtb infection. Copyright © 2017 Elsevier Inc. All rights reserved.

Sero-epidemiology of hepatitis B markers in the population of Tuscany, Central Italy, 20 years after the implementation of universal vaccination

PubMed Central

Boccalini, Sara; Pellegrino, Elettra; Tiscione, Emila; Pesavento, Giovanna; Bechini, Angela; Levi, Miriam; Rapi, Stefano; Mercurio, Stefano; Mannelli, Francesco; Peruzzi, Marta; Berardi, Cesare; Bonanni, Paolo

2013-01-01

Italy was one of the first industrialized countries to introduce a program of universal vaccination against hepatitis B in 1991. Twenty years later we verified the impact of universal immunisation on the epidemiology of hepatitis B infection by analyzing the prevalence of specific viral markers (anti-HBs, anti-HBc and HBsAg). The ELISA tests were performed on residual blood samples collected by 0.05% of the resident population aged 1-50 years in Tuscany (Italy). About 63% of subjects aged < 30 years were anti-HBs positive compared to about 25% in older subjects, without differences between genders. About 22% of subjects over 40 years were anti-HBc-positive compared to 5% in the younger age groups. The number of HBsAg-positive subjects was almost 10 fold higher in the unvaccinated age groups than in the cohorts involved in the universal vaccination program. The results of our study show the persisting high anti-HBs reactivity in vaccinated cohorts, while HBV markers related to natural exposure or persistent infection remain remarkably higher in older age groups. This sero-epidemiological study supports with prevalence data the downward incidence trend of acute hepatitis B highlighted by epidemiological surveillance systems, and corroborates the forecast for elimination of hepatitis B in Italy in a few decades. PMID:23354158

Prevalence of hepatitis A and B markers and vaccine indication in cirrhotic patients evaluated for liver transplantation in Spain.

PubMed

Aoufi, S; Pascasio, J M; Sousa, J M; Sayago, M; Ferrer, M T; Gómez-Delgado, E; De la Cruz, M D; Alamo, J M; Gómez-Bravo, M A; Bernardos, A; Márquez, J L

2008-11-01

Vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV) is generally recommended for patients with chronic liver disease and those evaluated for liver transplantation in the absence of immunity. HAV and HBV infections after liver transplantation are frequent and associated with a worse prognosis. The data suggest that the number of patients with chronic liver disease without naturally acquired immunity against HAV and HBV is substantial, and that new vaccination strategies are needed. The aim of this study was to determine the level of immunity from hepatitis A and B infections and the need for HBV and HAV vaccination among cirrhotic patients evaluated for liver transplantation. We studied HBV and HAV serological markers (HbsAg, anti-HBc, anti-HBs, IgG anti-HAV) in 451 cirrhotic patients evaluated for liver transplantation to investigate the association with gender, age, and etiology of cirrhosis. Negative HBV markers were observed in 57% of patients with 43% displaying one positive HBV marker: HBsAg (+), 9.5%; anti-HBc (+)/anti-HBs (-), 11.5%; anti-HBc (-)/anti-HBs(+), 4.2%; anti-HBc(+)/anti-HBs(+), 17.7%. HBV vaccine indication established in 68.5% of patients was greater among women and hepatitis C virus-negative patients. No differences were observed in age or cause of cirrhosis. HAV vaccination indicated in 6.7% of patients (IgG anti-HVA-negative) was greater among patients with negative HBV markers (9.3% vs 3.3%, P = .018) and younger patients (25.3% of patients vaccine among cirrhotic patients evaluated for liver transplantation, as is time for HAV vaccine, especially among patients younger than 45 years of age.

Vaccines for Leprosy and Tuberculosis: Opportunities for Shared Research, Development, and Application

PubMed Central

Coppola, Mariateresa; van den Eeden, Susan J. F.; Robbins, Naoko; Wilson, Louis; Franken, Kees L. M. C.; Adams, Linda B.; Gillis, Tom P.; Ottenhoff, Tom H. M.; Geluk, Annemieke

2018-01-01

Tuberculosis (TB) and leprosy still represent significant public health challenges, especially in low- and lower middle-income countries. Both poverty-related mycobacterial diseases require better tools to improve disease control. For leprosy, there has been an increased emphasis on developing tools for improved detection of infection and early diagnosis of disease. For TB, there has been a similar emphasis on such diagnostic tests, while increased research efforts have also focused on the development of new vaccines. Bacille Calmette–Guérin (BCG), the only available TB vaccine, provides insufficient and inconsistent protection to pulmonary TB in adults. The impact of BCG on leprosy, however, is significant, and the introduction of new TB vaccines that might replace BCG could, therefore, have serious impact also on leprosy. Given the similarities in antigenic makeup between the pathogens Mycobacterium tuberculosis (Mtb) and M. leprae, it is well possible, however, that new TB vaccines could cross-protect against leprosy. New TB subunit vaccines currently evaluated in human phase I and II studies indeed often contain antigens with homologs in M. leprae. In this review, we discuss pre-clinical studies and clinical trials of subunit or whole mycobacterial vaccines for TB and leprosy and reflect on the development of vaccines that could provide protection against both diseases. Furthermore, we provide the first preclinical evidence of such cross-protection by Mtb antigen 85B (Ag85B)-early secretory antigenic target (ESAT6) fusion recombinant proteins in in vivo mouse models of Mtb and M. leprae infection. We propose that preclinical integration and harmonization of TB and leprosy research should be considered and included in global strategies with respect to cross-protective vaccine research and development. PMID:29535713

High Antigen Dose Is Detrimental to Post-Exposure Vaccine Protection against Tuberculosis.

PubMed

Billeskov, Rolf; Lindenstrøm, Thomas; Woodworth, Joshua; Vilaplana, Cristina; Cardona, Pere-Joan; Cassidy, Joseph P; Mortensen, Rasmus; Agger, Else Marie; Andersen, Peter

2017-01-01

Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), causes 1.8M deaths annually. The current vaccine, BCG, has failed to eradicate TB leaving 25% of the world's population with latent Mtb infection (LTBI), and 5-10% of these people will reactivate and develop active TB. An efficient therapeutic vaccine targeting LTBI could have an enormous impact on global TB incidence, and could be an important aid in fighting multidrug resistance, which is increasing globally. Here we show in a mouse model using the H56 (Ag85B-ESAT-6-Rv2660) TB vaccine candidate that post-exposure, but not preventive, vaccine protection requires low vaccine antigen doses for optimal protection. Loss of protection from high dose post-exposure vaccination was not associated with a loss of overall vaccine response magnitude, but rather with greater differentiation and lower functional avidity of vaccine-specific CD4 T cells. High vaccine antigen dose also led to a decreased ability of vaccine-specific CD4 T cells to home into the Mtb-infected lung parenchyma, a recently discovered important feature of T cell protection in mice. These results underscore the importance of T cell quality rather than magnitude in TB-vaccine protection, and the significant role that antigen dosing plays in vaccine-mediated protection.

Improving birth dose coverage of hepatitis B vaccine.

PubMed Central

Hipgrave, David B.; Maynard, James E.; Biggs, Beverley-Ann

2006-01-01

Administration of a birth dose of hepatitis B vaccine (HepB vaccine) to neonates is recommended to prevent mother-to-infant transmission and chronic infection with the hepatitis B virus (HBV). Although manufacturers recommend HepB vaccine distribution and storage at 2-8 degrees C, recognition of the heat stability of hepatitis B surface antigen stimulated research into its use after storage at, or exposure to, ambient or high temperatures. Storage of HepB vaccine at ambient temperatures would enable birth dosing for neonates delivered at home in remote areas or at health posts lacking refrigeration. This article reviews the current evidence on the thermostability of HepB vaccine when stored outside the cold chain (OCC). The reports reviewed show that the vaccines studied were safe and effective whether stored cold or OCC. Field and laboratory data also verifies the retained potency of the vaccine after exposure to heat. The attachment of a highly stable variety of a vaccine vial monitor (measuring cumulative exposure to heat) on many HepB vaccines strongly supports policies allowing their storage OCC, when this will benefit birth dose coverage. We recommend that this strategy be introduced to improve birth dose coverage, especially in rural and remote areas. Concurrent monitoring and evaluation should be undertaken to affirm the safe implementation of this strategy, and assess its cost, feasibility and effect on reducing HBV infection rates. Meanwhile, release of manufacturer data verifying the potency of currently available HepB vaccines after exposure to heat will increase confidence in the use of vaccine vial monitors as a managerial tool during storage of HepB vaccine OCC. PMID:16501717

[Immunobiologic characteristics of a recombinant Listeria monocytogenes expressing Mycobacterium tuberculosis antigens].

PubMed

Yin, Yuelan; Zhao, Dan; Kang, Meiqin; Tan, Weijun; Lian, Kai; Hu, Maozhi; Chen, Xiang; Pan, Zhiming; Jiao, Xin'an

2013-12-04

Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis complex. Hence, novel vaccines against TB are urgently needed and important to the public health. Immunobiologic characteristics of a recombinant attenuated Listeria monocytogenes strain LMdeltahly: :Ag85b-esat-6 was evaluated. LMdeltahly: :Ag85b-esat-6 had lost the hemolytic activity. It was completely cleared from the livers and spleens of mice 5 days after inoculation via intravenous route. Furthermore, the LD50 of the recombinant strain increased by 4 Logs comparing to that of the parent strain. Histopathology reveals no obvious pathological changes following administration of the recombinant strain to mice, indicating its safety. In addition, the potential protective immune response was evaluated on C57BL/6 mice via intravenous immunization route. The results indicate that the antigen delivered by the recombination LM could induce Th1 type immune response and elicit strong cytotoxic lymphocyte effect against Ag85B-ESAT-6. Thus, LMdeltahly::Ag85b-esat-6 had high safety to mice, and could be used as a novel vaccines candidate for preventing tuberculosis.

9 CFR 85.8 - Interstate movement of swine from a qualified negative gene-altered vaccinated herd.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Interstate movement of swine from a... (INCLUDING POULTRY) AND ANIMAL PRODUCTS PSEUDORABIES § 85.8 Interstate movement of swine from a qualified negative gene-altered vaccinated herd. Swine from a qualified negative gene-altered vaccinated herd, and...

9 CFR 85.8 - Interstate movement of swine from a qualified negative gene-altered vaccinated herd.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Interstate movement of swine from a... (INCLUDING POULTRY) AND ANIMAL PRODUCTS PSEUDORABIES § 85.8 Interstate movement of swine from a qualified negative gene-altered vaccinated herd. Swine from a qualified negative gene-altered vaccinated herd, and...

9 CFR 85.8 - Interstate movement of swine from a qualified negative gene-altered vaccinated herd.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Interstate movement of swine from a... (INCLUDING POULTRY) AND ANIMAL PRODUCTS PSEUDORABIES § 85.8 Interstate movement of swine from a qualified negative gene-altered vaccinated herd. Swine from a qualified negative gene-altered vaccinated herd, and...

9 CFR 85.8 - Interstate movement of swine from a qualified negative gene-altered vaccinated herd.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Interstate movement of swine from a... (INCLUDING POULTRY) AND ANIMAL PRODUCTS PSEUDORABIES § 85.8 Interstate movement of swine from a qualified negative gene-altered vaccinated herd. Swine from a qualified negative gene-altered vaccinated herd, and...

Process of assay selection and optimization for the study of case and control samples from a phase IIb efficacy trial of a candidate tuberculosis vaccine, MVA85A.

PubMed

Harris, Stephanie A; Satti, Iman; Matsumiya, Magali; Stockdale, Lisa; Chomka, Agnieszka; Tanner, Rachel; O'Shea, Matthew K; Manjaly Thomas, Zita-Rose; Tameris, Michele; Mahomed, Hassan; Scriba, Thomas J; Hanekom, Willem A; Fletcher, Helen A; McShane, Helen

2014-07-01

The first phase IIb safety and efficacy trial of a new tuberculosis vaccine since that for BCG was completed in October 2012. BCG-vaccinated South African infants were randomized to receive modified vaccinia virus Ankara, expressing the Mycobacterium tuberculosis antigen 85A (MVA85A), or placebo. MVA85A did not significantly boost the protective effect of BCG. Cryopreserved samples provide a unique opportunity for investigating the correlates of the risk of tuberculosis disease in this population. Due to the limited amount of sample available from each infant, preliminary work was necessary to determine which assays and conditions give the most useful information. Peripheral blood mononuclear cells (PBMC) were stimulated with antigen 85A (Ag85A) and purified protein derivative from M. tuberculosis in an ex vivo gamma interferon (IFN-γ) enzyme-linked immunosorbent spot assay (ELISpot) and a Ki67 proliferation assay. The effects of a 2-h or overnight rest of thawed PBMC on ELISpot responses and cell populations were determined. Both the ELISpot and Ki67 assays detected differences between the MVA85A and placebo groups, and the results correlated well. The cell numbers and ELISpot responses decreased significantly after an overnight rest, and surface flow cytometry showed a significant loss of CD4(+) and CD8(+) T cells. Of the infants tested, 50% had a positive ELISpot response to a single pool of flu, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) (FEC) peptides. This pilot work has been essential in determining the assays and conditions to be used in the correlate study. Moving forward, PBMC will be rested for 2 h before assay setup. The ELISpot assay, performed in duplicate, will be selected over the Ki67 assay, and further work is needed to evaluate the effect of high FEC responses on vaccine-induced immunity and susceptibility to tuberculosis disease. Copyright © 2014 Harris et al.

In situ solid-state fabrication of hybrid AgCl/AgI/AgIO3 with improved UV-to-visible photocatalytic performance.

PubMed

Xie, Jing; Cao, Yali; Jia, Dianzeng; Li, Yizhao; Wang, Kun; Xu, Hui

2017-09-28

The AgCl/AgI/AgIO 3 composites were synthesized through a one-pot room-temperature in situ solid-state approach with the feature of convenient and eco-friendly. The as-prepared composites exhibit superior photocatalytic performance than pure AgIO 3 for the degradation of methyl orange (MO) under both UV and visible light irradiation. The photodegradation rate toward MO of the AgCl/AgI/AgIO 3 photocatalyst can reach 100% after 12 min irradiation under UV light, or 85.4% after 50 min irradiation under visible light, being significantly higher than AgCl, AgI, AgIO 3 and AgI/AgIO 3 . In addition, the AgCl/AgI/AgIO 3 photocatalyst possesses strong photooxidation ability for the degradation of rhodamine B (RhB), methylene blue (MB), phenol, bisphenol A (BPA) and tetracycline hydrochloride under visible light irradiation. The reactive species capture experiments confirmed that the h + and •O 2- play an essential role during the photocatalytic process under UV light or visible light irradiation. The enhanced effect may be beneficial from the enhanced light adsorption in full spectrum and increased separation efficiency of photogenerated hole-electron pairs, which can be ascribed to the synergistic effect among AgCl, AgI and AgIO 3 nanoplates in AgCl/AgI/AgIO 3 composites.

Simultaneous Subcutaneous and Intranasal Administration of a CAF01-Adjuvanted Chlamydia Vaccine Elicits Elevated IgA and Protective Th1/Th17 Responses in the Genital Tract

PubMed Central

Wern, Jeanette Erbo; Sorensen, Maria Rathmann; Olsen, Anja Weinreich; Andersen, Peter; Follmann, Frank

2017-01-01

The selection of any specific immunization route is critical when defining future vaccine strategies against a genital infection like Chlamydia trachomatis (C.t.). An optimal Chlamydia vaccine needs to elicit mucosal immunity comprising both neutralizing IgA/IgG antibodies and strong Th1/Th17 responses. A strategic tool to modulate this immune profile and mucosal localization of vaccine responses is to combine parenteral and mucosal immunizations routes. In this study, we investigate whether this strategy can be adapted into a two-visit strategy by simultaneous subcutaneous (SC) and nasal immunization. Using a subunit vaccine composed of C.t. antigens (Ags) adjuvanted with CAF01, a Th1/Th17 promoting adjuvant, we comparatively evaluated Ag-specific B and T cell responses and efficacy in mice following SC and simultaneous SC and nasal immunization (SIM). We found similar peripheral responses with regard to interferon gamma and IL-17 producing Ag-specific splenocytes and IgG serum levels in both vaccine strategies but in addition, the SIM protocol also led to Ag-specific IgA responses and increased B and CD4+ T cells in the lung parenchyma, and in lower numbers also in the genital tract (GT). Following vaginal infection with C.t., we observed that SIM immunization gave rise to an early IgA response and IgA-secreting plasma cells in the GT in contrast to SC immunization, but we were not able to detect more rapid recruitment of mucosal T cells. Interestingly, although SIM vaccination in general improved mucosal immunity we observed no improved efficacy against genital infection compared to SC, a finding that warrants for further investigation. In conclusion, we demonstrate a novel vaccination strategy that combines systemic and mucosal immunity in a two-visit strategy. PMID:28567043

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.

Minipigs as an Animal Model for Dermal Vaccine Delivery

PubMed Central

Ploemen, Ivo HJ; Hirschberg, Hoang JHB; Kraan, Heleen; Zeltner, Adrian; van Kuijk, Sandra; Lankveld, Danielle PK; Royals, Michael; Kersten, Gideon FA; Amorij, Jean-Pierre

2014-01-01

Appropriate animal models for intradermal vaccine delivery are scarce. Given the high similarity of their skin anatomy to that of humans, minipigs may be a suitable model for dermal vaccine delivery. Here we describe the immunization of Göttingen minipigs by using intradermal and intramuscular delivery of hepatitis B surface antigen (HBsAg). Intradermal vaccine delivery by needle and syringe and by needle-free jet injection induced humoral antiHBsAg responses. Priming immunization by using the disposable syringe jet injector (DSJI) resulted in a higher antibody titer than did conventional intradermal immunization and a titer comparable to that after intramuscular vaccination with HBsAg and Al(OH)3 adjuvant. This study highlights the utility of the minipig model in vaccine studies assessing the efficacy of conventional and novel methods of dermal delivery. Moreover, we include suggestions regarding working with minipigs during dermal vaccine delivery studies, thereby fostering future work in this area of vaccinology. PMID:24512961

7 CFR 301.85-2b - Exempted articles. 1

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 5 2014-01-01 2014-01-01 false Exempted articles. 1 301.85-2b Section 301.85-2b... § 301.85-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines and other provisions of this subpart. (a) The following articles are...

7 CFR 301.85-2b - Exempted articles. 1

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 5 2011-01-01 2011-01-01 false Exempted articles. 1 301.85-2b Section 301.85-2b... § 301.85-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines and other provisions of this subpart. (a) The following articles are...

7 CFR 301.85-2b - Exempted articles. 1

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Exempted articles. 1 301.85-2b Section 301.85-2b... § 301.85-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines and other provisions of this subpart. (a) The following articles are...

7 CFR 301.85-2b - Exempted articles. 1

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 5 2013-01-01 2013-01-01 false Exempted articles. 1 301.85-2b Section 301.85-2b... § 301.85-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines and other provisions of this subpart. (a) The following articles are...

7 CFR 301.85-2b - Exempted articles. 1

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 5 2012-01-01 2012-01-01 false Exempted articles. 1 301.85-2b Section 301.85-2b... § 301.85-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines and other provisions of this subpart. (a) The following articles are...

Hepatitis B virus infections in families in which the mothers are negative but the fathers are positive for HBsAg.

PubMed

Takegoshi, Kunio; Zhang, Wei

2006-10-01

We studied a total of 37 families, in which HBsAg was positive in either or both of father and mother, to assess intra-familial transmission of hepatitis B virus (HBV). The HBsAg positive rate for children with HBsAg-negative mothers was significantly lower than that with positive mothers (4 of 31, 12.9% versus 18 of 32, 56.3%, p<0.01) of course. However, there were three families in which the infection source for children was thought to be fathers, not mothers, i.e., of eight children in these three families with HBsAg +/- father/mother pairs, 4 (50%) were positive for both HBsAg and HBV DNA of genotypes identical to those of their fathers, and another child was positive for HBcAb despite being negative for HBsAg. Interestingly, moreover, all the mothers in these three families were HBcAb-positive even though HBsAg-negative, suggesting that not only father-to-child but also inter-spouse HBV transmission might have occurred. With these findings we would suggest that all the family members with HBsAg-positive fathers should receive HBV vaccine, let alone for those with HBsAg-positive mothers.

Analysis of B Cell Repertoire Dynamics Following Hepatitis B Vaccination in Humans, and Enrichment of Vaccine-specific Antibody Sequences.

PubMed

Galson, Jacob D; Trück, Johannes; Fowler, Anna; Clutterbuck, Elizabeth A; Münz, Márton; Cerundolo, Vincenzo; Reinhard, Claudia; van der Most, Robbert; Pollard, Andrew J; Lunter, Gerton; Kelly, Dominic F

2015-12-01

Generating a diverse B cell immunoglobulin repertoire is essential for protection against infection. The repertoire in humans can now be comprehensively measured by high-throughput sequencing. Using hepatitis B vaccination as a model, we determined how the total immunoglobulin sequence repertoire changes following antigen exposure in humans, and compared this to sequences from vaccine-specific sorted cells. Clonal sequence expansions were seen 7 days after vaccination, which correlated with vaccine-specific plasma cell numbers. These expansions caused an increase in mutation, and a decrease in diversity and complementarity-determining region 3 sequence length in the repertoire. We also saw an increase in sequence convergence between participants 14 and 21 days after vaccination, coinciding with an increase of vaccine-specific memory cells. These features allowed development of a model for in silico enrichment of vaccine-specific sequences from the total repertoire. Identifying antigen-specific sequences from total repertoire data could aid our understanding B cell driven immunity, and be used for disease diagnostics and vaccine evaluation.

A Randomized Controlled Trial to Evaluate a Potential Hepatitis B Booster Vaccination Strategy Using Combined Hepatitis A and B Vaccine.

PubMed

Li, Fangjun; Hu, Yuansheng; Zhou, Youming; Chen, Lixin; Xia, Wei; Song, Yufei; Tan, Zhengliang; Gao, Lidong; Yang, Zhong; Zeng, Gang; Han, Xing; Li, Junhua; Li, Jing

2017-05-01

Booster doses could play a major role in no responders or low responders to primary hepatitis B (HB) vaccine. Planed time point for hepatitis A vaccination in China provides a good opportunity to carry out HB booster dose by using combined hepatitis A and B vaccine. A randomized, double-blinded clinical trial was conducted to compare the immunogenicity and safety of toddlers 18-24 months of age receiving 3 different vaccination regimens: 2 doses of inactivated hepatitis A vaccine (group 1), 1 dose of inactivated hepatitis A vaccine plus 1 dose of combined hepatitis A and B vaccine (group 2) or 2 doses of combined hepatitis A and B vaccine (group 3). All 3 groups showed 100% seroprotection for antihepatitis A virus antibody after vaccination. Seroprotection rate for anti-HB antibody before vaccination ranged from 79.5% to 92.9% in the 3 groups. After second inoculation, anti-HBs seroprotection increased from 92.9% to 100% in group 2 with postvaccination geometric mean concentration (GMC) of 2258.3 mIU/mL and from 79.5% to 98.9% in group 3 with postvaccination GMC of 2055.3 mIU/mL. The adverse events were not statistically different among groups (P = 0.345). Combined hepatitis A and B vaccine could stimulate high level of both antihepatitis A virus and anti-HBs antibodies and not increase adverse events, providing a new choice for HB booster.

Conservation in gene encoding Mycobacterium tuberculosis antigen Rv2660 and a high predicted population coverage of H56 multistage vaccine in South Africa.

PubMed

Perez-Martinez, Angy P; Ong, Edison; Zhang, Lixin; Marrs, Carl F; He, Yongqun; Yang, Zhenhua

2017-11-01

H56/AERAS-456+IC31 (H56), composed of two early secretion proteins, Ag85B and ESAT-6, and a latency associated protein, Rv2660, and the IC31 Intercell adjuvant, is a new fusion subunit vaccine candidate designed to induce immunity against both new infection and reactivation of latent tuberculosis infection. Efficacy of subunit vaccines may be affected by the diversity of vaccine antigens among clinical strains and the extent of recognition by the diverse HLA molecules in the recipient population. Although a previous study showed the conservative nature of Ag85B- and ESAT-6-encoding genes, genetic diversity of Rv2660c that encodes RV2660 is largely unknown. The population coverage of H56 as a whole yet remains to be assessed. The present study was conducted to address these important knowledge gaps. DNA sequence analysis of Rv2660c found no variation among 83 of the 84 investigated clinical strains belonging to four genetic lineages. H56 was predicted to have as high as 99.6% population coverage in the South Africa population using the Immune Epitope Database (IEDB) Population Coverage Tool. Further comparison of H56 population coverage between South African Blacks and Caucasians based on the phenotypic frequencies of binding MHC Class I and Class II supertype alleles found that all of the nine MHC-I and six of eight MHC-II human leukocyte antigen (HLA) supertype alleles analyzed were significantly differentially expressed between the two subpopulations. This finding suggests the presence of race-specific functional binding motifs of MHC-I and MHC-II HLA alleles, which, in turn, highlights the importance of including diverse populations in vaccine clinical evaluation. In conclusion, H56 vaccine is predicted to have a promising population coverage in South Africa; this study demonstrates the utility of integrating comparative genomics and bioinformatics in bridging animal and clinical studies of novel TB vaccines. Copyright © 2017 Elsevier B.V. All rights reserved.

Quick assessment of the influence of the Hepatitis B vaccine event on children's vaccination.

PubMed

Yue, Chenyan; Sun, Xiaojin; Wei, Ning; Yu, Wenzhou; Cui, Fuqiang; Wang, Huaqing; Li, Li; Zhang, Lijie; Shi, Guoqing; An, Zhijie

2016-10-02

From December 2013 to January 2014, a large number of medias in China reported negative information about Hepatitis B vaccine (HepB) safety issues using eye-catching titles, such as "3 infants in Hunan inoculated with HepB occurred adverse event, and 2 died," and that caused crisis of confidence in vaccination, which we called "HepB event." The progress of "HepB event" could be divided into 3 stages which were initiation, peak and ending stages. In order to evaluate the influence of "HepB event" on the attitudes of participants toward Hepatitis B vaccine safety and their intention of vaccinating their children in different stages, and provide evidence for authority departments as soon as possible to take measures to prevent decrease of HepB coverage rate, a quick field investigation was carried out. Using convenience sampling methods during the initiation, peak and ending stages of the "HepB event." In the 3 stages of the "HepB event," the awareness rate of the event among participants was rapidly rising, showing that the participants paid great attention to the event, and the information was spread very quickly. The proportion of participants who knew the event but thought that the Hepatitis B vaccine was unsafe were 31%, 37% and 26% respectively in 3 stages. In addition, the acceptance of vaccination by the participants was influenced, the proportion of participants who would like to delay or reject vaccinating their children was up to 43% in the peak stage of the event. The "HepB event" had impacted on the participants' confidence in the safety of Hepatitis B vaccine. For such event, relevant authority departments need effectively communicate with the media and the public, and promptly issue positive information and the investigation result, thereby reducing the negative impact of the event, and improve the vaccine confidence among the public.

Characterisation of Antigen B Protein Species Present in the Hydatid Cyst Fluid of Echinococcus canadensis G7 Genotype

PubMed Central

Folle, Ana Maite; Kitano, Eduardo S.; Lima, Analía; Gil, Magdalena; Cucher, Marcela; Mourglia-Ettlin, Gustavo; Iwai, Leo K.; Rosenzvit, Mara; Batthyány, Carlos

2017-01-01

The larva of cestodes belonging to the Echinococcus granulosus sensu lato (s.l.) complex causes cystic echinococcosis (CE). It is a globally distributed zoonosis with significant economic and public health impact. The most immunogenic and specific Echinococcus-genus antigen for human CE diagnosis is antigen B (AgB), an abundant lipoprotein of the hydatid cyst fluid (HF). The AgB protein moiety (apolipoprotein) is encoded by five genes (AgB1-AgB5), which generate mature 8 kDa proteins (AgB8/1-AgB8/5). These genes seem to be differentially expressed among Echinococcus species. Since AgB immunogenicity lies on its protein moiety, differences in AgB expression within E. granulosus s.l. complex might have diagnostic and epidemiological relevance for discriminating the contribution of distinct species to human CE. Interestingly, AgB2 was proposed as a pseudogene in E. canadensis, which is the second most common cause of human CE, but proteomic studies for verifying it have not been performed yet. Herein, we analysed the protein and lipid composition of AgB obtained from fertile HF of swine origin (E. canadensis G7 genotype). AgB apolipoproteins were identified and quantified using mass spectrometry tools. Results showed that AgB8/1 was the major protein component, representing 71% of total AgB apolipoproteins, followed by AgB8/4 (15.5%), AgB8/3 (13.2%) and AgB8/5 (0.3%). AgB8/2 was not detected. As a methodological control, a parallel analysis detected all AgB apolipoproteins in bovine fertile HF (G1/3/5 genotypes). Overall, E. canadensis AgB comprised mostly AgB8/1 together with a heterogeneous mixture of lipids, and AgB8/2 was not detected despite using high sensitivity proteomic techniques. This endorses genomic data supporting that AgB2 behaves as a pseudogene in G7 genotype. Since recombinant AgB8/2 has been found to be diagnostically valuable for human CE, our findings indicate that its use as antigen in immunoassays could contribute to false negative results in

Characterisation of Antigen B Protein Species Present in the Hydatid Cyst Fluid of Echinococcus canadensis G7 Genotype.

PubMed

Folle, Ana Maite; Kitano, Eduardo S; Lima, Analía; Gil, Magdalena; Cucher, Marcela; Mourglia-Ettlin, Gustavo; Iwai, Leo K; Rosenzvit, Mara; Batthyány, Carlos; Ferreira, Ana María

2017-01-01

The larva of cestodes belonging to the Echinococcus granulosus sensu lato (s.l.) complex causes cystic echinococcosis (CE). It is a globally distributed zoonosis with significant economic and public health impact. The most immunogenic and specific Echinococcus-genus antigen for human CE diagnosis is antigen B (AgB), an abundant lipoprotein of the hydatid cyst fluid (HF). The AgB protein moiety (apolipoprotein) is encoded by five genes (AgB1-AgB5), which generate mature 8 kDa proteins (AgB8/1-AgB8/5). These genes seem to be differentially expressed among Echinococcus species. Since AgB immunogenicity lies on its protein moiety, differences in AgB expression within E. granulosus s.l. complex might have diagnostic and epidemiological relevance for discriminating the contribution of distinct species to human CE. Interestingly, AgB2 was proposed as a pseudogene in E. canadensis, which is the second most common cause of human CE, but proteomic studies for verifying it have not been performed yet. Herein, we analysed the protein and lipid composition of AgB obtained from fertile HF of swine origin (E. canadensis G7 genotype). AgB apolipoproteins were identified and quantified using mass spectrometry tools. Results showed that AgB8/1 was the major protein component, representing 71% of total AgB apolipoproteins, followed by AgB8/4 (15.5%), AgB8/3 (13.2%) and AgB8/5 (0.3%). AgB8/2 was not detected. As a methodological control, a parallel analysis detected all AgB apolipoproteins in bovine fertile HF (G1/3/5 genotypes). Overall, E. canadensis AgB comprised mostly AgB8/1 together with a heterogeneous mixture of lipids, and AgB8/2 was not detected despite using high sensitivity proteomic techniques. This endorses genomic data supporting that AgB2 behaves as a pseudogene in G7 genotype. Since recombinant AgB8/2 has been found to be diagnostically valuable for human CE, our findings indicate that its use as antigen in immunoassays could contribute to false negative results in

High Antigen Dose Is Detrimental to Post-Exposure Vaccine Protection against Tuberculosis

PubMed Central

Billeskov, Rolf; Lindenstrøm, Thomas; Woodworth, Joshua; Vilaplana, Cristina; Cardona, Pere-Joan; Cassidy, Joseph P.; Mortensen, Rasmus; Agger, Else Marie; Andersen, Peter

2018-01-01

Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), causes 1.8M deaths annually. The current vaccine, BCG, has failed to eradicate TB leaving 25% of the world’s population with latent Mtb infection (LTBI), and 5–10% of these people will reactivate and develop active TB. An efficient therapeutic vaccine targeting LTBI could have an enormous impact on global TB incidence, and could be an important aid in fighting multidrug resistance, which is increasing globally. Here we show in a mouse model using the H56 (Ag85B-ESAT-6-Rv2660) TB vaccine candidate that post-exposure, but not preventive, vaccine protection requires low vaccine antigen doses for optimal protection. Loss of protection from high dose post-exposure vaccination was not associated with a loss of overall vaccine response magnitude, but rather with greater differentiation and lower functional avidity of vaccine-specific CD4 T cells. High vaccine antigen dose also led to a decreased ability of vaccine-specific CD4 T cells to home into the Mtb-infected lung parenchyma, a recently discovered important feature of T cell protection in mice. These results underscore the importance of T cell quality rather than magnitude in TB-vaccine protection, and the significant role that antigen dosing plays in vaccine-mediated protection. PMID:29379507

Overview of expression of hepatitis B surface antigen in transgenic plants.

PubMed

Guan, Zheng-jun; Guo, Bin; Huo, Yan-lin; Guan, Zheng-ping; Wei, Ya-hui

2010-10-28

Hepatitis B virus (HBV), a pathogen for chronic liver infection, afflicts more than 350 million people world-wide. The effective way to control the virus is to take HBV vaccine. Hepatitis B surface antigen (HBsAg) is an effective protective antigen suitable for vaccine development. At present, "edible" vaccine based on transgenic plants is one of the most promising directions in novel types of vaccines. HBsAg production from transgenic plants has been carried out, and the transgenic plant expression systems have developed from model plants (such as tobacco, potato and tomato) to other various plant platforms. Crude or purified extracts of transformed plants have been found to conduct immunological responses and clinical trials for hepatitis B, which gave the researches of plant-based HBsAg production a big boost. The aim of this review was to summarize the recent data about plant-based HBsAg development including molecular biology of HBsAg gene, selection of expression vector, the expression of HBsAg gene in plants, as well as corresponding immunological responses in animal models or human. Copyright © 2010 Elsevier Ltd. All rights reserved.

Freeze-thaw stress of Alhydrogel ® alone is sufficient to reduce the immunogenicity of a recombinant hepatitis B vaccine containing native antigen.

PubMed

Clapp, Tanya; Munks, Michael W; Trivedi, Ruchit; Kompella, Uday B; Braun, LaToya Jones

2014-06-24

Preventing losses in vaccine potency due to accidental freezing has recently become a topic of interest for improving vaccines. All vaccines with aluminum-containing adjuvants are susceptible to such potency losses. Recent studies have described excipients that protect the antigen from freeze-induced inactivation, prevent adjuvant agglomeration and retain potency. Although these strategies have demonstrated success, they do not provide a mechanistic understanding of freeze-thaw (FT) induced potency losses. In the current study, we investigated how adjuvant frozen in the absence of antigen affects vaccine immunogenicity and whether preventing damage to the freeze-sensitive recombinant hepatitis B surface antigen (rHBsAg) was sufficient for maintaining vaccine potency. The final vaccine formulation or Alhydrogel(®) alone was subjected to three FT-cycles. The vaccines were characterized for antigen adsorption, rHBsAg tertiary structure, particle size and charge, adjuvant elemental content and in-vivo potency. Particle agglomeration of either vaccine particles or adjuvant was observed following FT-stress. In vivo studies demonstrated no statistical differences in IgG responses between vaccines with FT-stressed adjuvant and no adjuvant. Adsorption of rHBsAg was achieved; regardless of adjuvant treatment, suggesting that the similar responses were not due to soluble antigen in the frozen adjuvant-containing formulations. All vaccines with adjuvant, including the non-frozen controls, yielded similar, blue-shifted fluorescence emission spectra. Immune response differences could not be traced to differences in the tertiary structure of the antigen in the formulations. Zeta potential measurements and elemental content analyses suggest that FT-stress resulted in a significant chemical alteration of the adjuvant surface. This data provides evidence that protecting a freeze-labile antigen from subzero exposure is insufficient to maintain vaccine potency. Future studies should

[Vaccination against hepatitis B. Impact of vaccination programmes after 20 years of use in Spain. Is it time for a change?].

PubMed

Arístegui Fernández, Javier; Díez-Domingo, Javier; Marés Bermúdez, Josep; Martinón Torres, Federico

2015-02-01

The highest incidence rate of hepatitis B (HB) in Spain is detected in adults between 20 and 54 years old, whereas the incidence in children under 1 year old is almost nil. The low prevalence of HB in children under 1 year is mainly due to the success of gestational screening strategies for the detection of HBsAg(+) in pregnant women, and vaccination campaigns during childhood. Currently, in Spain, the last dose of the HB included in the national childhood immunization program is administered at 6 months of age, although some studies show that delaying the age of the administration of the last dose of HB vaccine and increasing the time between doses, may improve immune memory by offering greater protection against this virus in the adulthood. In this article, the impact of HB vaccination in Spain is reviewed, and other potential vaccination strategies in our environment are discussed, such as extending the interval between doses, and administering the last dose in the second year of life, adapting the valid strategy in Spain to the current epidemiological context in order to reduce the prevalence of HB in adulthood. Copyright © 2015. Published by Elsevier España.

UK parents’ attitudes towards meningococcal group B (MenB) vaccination: a qualitative analysis

PubMed Central

Jackson, Cath; Yarwood, Joanne; Saliba, Vanessa

2017-01-01

Objectives (1) To explore existing knowledge of, and attitudes, to group B meningococcal disease and serogroup B meningococcal (MenB) vaccine among parents of young children. (2) To seek views on their information needs. Design Cross-sectional qualitative study using individual and group interviews conducted in February and March 2015, prior to the introduction of MenB vaccine (Bexsero) into the UK childhood immunisation schedule. Setting Community centres, mother and toddler groups, parents’ homes and workplaces in London and Yorkshire. Participants 60 parents of children under 2 years of age recruited via mother and baby groups and via an advert posted to a midwife-led Facebook group. Results Although recognising the severity of meningitis and septicaemia, parents’ knowledge of group B meningococcal disease and MenB vaccine was poor. While nervous about fever, most said they would take their child for MenB vaccination despite its link to fever. Most parents had liquid paracetamol at home. Many were willing to administer it after MenB vaccination as a preventive measure, although some had concerns. There were mixed views on the acceptability of four vaccinations at the 12-month booster visit; some preferred one visit, while others favoured spreading the vaccines over two visits. Parents were clear on the information they required before attending the immunisation appointment. Conclusions The successful implementation of the MenB vaccination programme depends on its acceptance by parents. In view of parents’ recognition of the severity of meningitis and septicaemia, and successful introduction of other vaccines to prevent bacterial meningitis and septicaemia, the MenB vaccination programme is likely to be successful. However, the need for additional injections, the likelihood of post-immunisation fever and its management are issues about which parents will need information and reassurance from healthcare professionals. Public Health England has developed

Occupational risks and hepatitis B vaccination status of dental auxiliaries in Nigeria.

PubMed

Azodo, C C; Ehigiator, O; Ojo, M A

2010-01-01

To assess the occupational exposure to needlestick and sharps injuries and hepatitis B vaccination status among dental auxiliaries. A descriptive cross-sectional survey of 83 dental auxiliaries was conducted that included 12 technologists, 11 therapists, 53 nurses/surgical assistants, and 7 record officers. The survey included demography, history of needlestick and sharps injury, hepatitis B vaccination, knowledge and attitude towards HIV-infected patients, and the dental auxiliaries' information needs on HIV-related issues. Of the 83 dental auxiliaries, 34 (41%) had experienced needlestick and sharps injury in the last 12 months. At the time of the study, only 43 (51.8%) had been immunized against hepatitis B. 62 (74.7%) of the respondents thought that it was easier to contract HIV than hepatitis B through needlestick in a dental clinic. 21 (25.3%) would not assist dentists treating HIV-positive patients. However, 76 (91.6%), a majority, agreed that they needed more information on HIV-related issues, with 59 (71.1%) specifying a single area of need and 17 (20.5%) more than one area of need. The single areas of need specified in descending order were infection control (n = 22, 26.5%), HIV counseling (n = 12, 14.5%), oral manifestations of HIV/AIDS (n = 11, 13.3%), postexposure prophylaxis (n = 9, 10.8%), and antiretroviral therapy (n = 5, 6.0%). The data from this survey underscore the urgent need for educational interventions to encourage safe work practices. Hepatitis B vaccination, HIV-related knowledge and proper postexposure prophylaxis are needed to prevent occupational transmission of blood-borne viruses. Copyright 2010 S. Karger AG, Basel.

Diabetes and Hepatitis B Vaccination

MedlinePlus

Diabetes and Hepatitis B Vaccination Information for Diabetes Educators What is hepatitis B? Hepatitis B is a contagious liver disease that results from infection with the hepatitis B virus. When first infected, a person can develop ...

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

[Effectiveness of rapid hepatitis B vaccination with different vaccine dosages and types in adults].

PubMed

Nie, L; Pang, X H; Zhang, Z; Ma, J X; Liu, X Y; Qiu, Q; Liang, Y; Li, Q; Zhang, W

2017-09-10

Objective: To evaluate the effectiveness of rapid hepatitis B vaccination with different vaccine dosages and types in adults. Methods: Adults who were aged ≥20 years, negative in the detections of 5 HBV serum markers or only anti-HBc positive were selected from Chaoyang district of Beijing. They were divided into 4 community-based specific groups and given three doses of 10 μg HepB-SCY vaccine, 20 μg HepB-SCY vaccine, 20 μg HepB-CHO vaccine and 10 μg HepB-HPY vaccine respectively at month 0, 1, and 2. Their blood samples were collected within 1-2 months after completing the three dose vaccination to test anti-HBs level by using chemiluminesent microparticle immunoassay. A face to face questionnaire survey was conducted, and χ (2) test, Mantel- Haensel χ (2) test, Kruskal-Wallis rank test and multiple logistic regression analysis were performed. Results: A total of 1 772 participants completed vaccination and observation. Their average age was 48.5 years, and 62.75 % of them were females. The anti-HBs positive rates in the groups of 10 μg HepB-SCY, 20 μg HepB-SCY, 20 μg HepB-CHO and 10 μg HepB-HPY vaccines were 79.49 % , 84.34 % , 82.50 % and 74.15 %, respectively ( P =0.005), and the geometric mean titers (GMT) were39.53 mIU/ml, 62.37 mIU/ml, 48.18 mIU/ml and 33.64 mIU/ml respectively ( P =0.025). The overall anti-HBs positive rate and GMT were 79.01 % and 41.18 mIU/ml. The anti-HBs GMT of 4 groups declined with age. The differences in anti-HBs GMT among 4 groups minimized with age. The result of logistic modeling indicated that vaccine type and dosage, age and smoking were associated with anti-HBs statistically after controlling the variables of"only anti-HBc positive or not"and"history of hepatitis B vaccination". Conclusion: Hepatitis B vaccination at dosage of 20 μg based on 0-1-2 month rapid schedule could achieved anti-HBs positive rates>80 % in middle aged and old people, which can be used as supplement of 0-1-6 month routine schedule.

Prediction of linear B-cell epitopes of hepatitis C virus for vaccine development

PubMed Central

2015-01-01

Background High genetic heterogeneity in the hepatitis C virus (HCV) is the major challenge of the development of an effective vaccine. Existing studies for developing HCV vaccines have mainly focused on T-cell immune response. However, identification of linear B-cell epitopes that can stimulate B-cell response is one of the major tasks of peptide-based vaccine development. Owing to the variability in B-cell epitope length, the prediction of B-cell epitopes is much more complex than that of T-cell epitopes. Furthermore, the motifs of linear B-cell epitopes in different pathogens are quite different (e. g. HCV and hepatitis B virus). To cope with this challenge, this work aims to propose an HCV-customized sequence-based prediction method to identify B-cell epitopes of HCV. Results This work establishes an experimentally verified dataset comprising the B-cell response of HCV dataset consisting of 774 linear B-cell epitopes and 774 non B-cell epitopes from the Immune Epitope Database. An interpretable rule mining system of B-cell epitopes (IRMS-BE) is proposed to select informative physicochemical properties (PCPs) and then extracts several if-then rule-based knowledge for identifying B-cell epitopes. A web server Bcell-HCV was implemented using an SVM with the 34 informative PCPs, which achieved a training accuracy of 79.7% and test accuracy of 70.7% better than the SVM-based methods for identifying B-cell epitopes of HCV and the two general-purpose methods. This work performs advanced analysis of the 34 informative properties, and the results indicate that the most effective property is the alpha-helix structure of epitopes, which influences the connection between host cells and the E2 proteins of HCV. Furthermore, 12 interpretable rules are acquired from top-five PCPs and achieve a sensitivity of 75.6% and specificity of 71.3%. Finally, a conserved promising vaccine candidate, PDREMVLYQE, is identified for inclusion in a vaccine against HCV. Conclusions This work

Immunogenicity of a novel, bivalent, plant-based oral vaccine against hepatitis B and human immunodeficiency viruses.

PubMed

Shchelkunov, Sergei N; Salyaev, Rurik K; Pozdnyakov, Sergei G; Rekoslavskaya, Natalia I; Nesterov, Andrei E; Ryzhova, Tatiana S; Sumtsova, Valentina M; Pakova, Natalia V; Mishutina, Uliana O; Kopytina, Tatiana V; Hammond, Rosemarie W

2006-07-01

A synthetic chimeric gene, TBI-HBS, encoding the immunogenic ENV and GAG epitopes of human immunodeficiency virus (HIV-1) and the surface protein antigen (HBsAg) of hepatitis B virus (HBV), was expressed in tomato plants. Tomato fruits containing the TBI-HBS antigen were fed to experimental mice and, on days 14 and 28 post-feeding, high levels of HIV- and HBV-specific antibodies were present in the serum and feces of the test animals. Intraperitoneal injection of a DNA vaccine directing synthesis of the same TBI-HBsAg antigen boosted the antibody response to HIV in the blood serum; however, it had no effect on the high level of antibodies produced to HBV.

Challenge with a hepatitis B vaccine in two cohorts of 4-7-year-old children primed with hexavalent vaccines: an open-label, randomised trial in Italy.

PubMed

Zanetti, Alessandro; Parlato, Antonino; Romanò, Luisa; Desole, Maria Giuseppina; Ferrera, Giuseppe; Giurdanella, Filippo; Zuliani, Massimo; Richard, Patrick; Thomas, Stéphane; Fiquet, Anne

2012-08-24

The anamnestic response to a challenge dose of vaccine can assess immune memory and protection against hepatitis B infection. This study investigated responses to a challenge dose of monovalent hepatitis B vaccine in children immunised with three doses of either Hexavac or Infanrix-Hexa during infancy. This open-label, randomised, controlled, four-arm study enrolled 410 healthy children aged 4-7 years who had received either Hexavac (n=201) or Infanrix-Hexa (n=209) at 3, 5 and 11 months of life. Children received a single intramuscular challenge dose of either hepatitis B vaccine, HBVaxPro (Hexavac, n=34; Infanrix-Hexa, n=28) or Engerix-B (Hexavac, n=167; Infanrix-Hexa, n=181). Hepatitis B surface antibody (anti-HBs) concentrations were measured before and 1 month after the challenge vaccine dose. The analysis was descriptive and no formal hypothesis was tested. One month post-challenge, 91.2% of children in the Hexavac group (95% confidence interval [CI] 86.3, 94.8) and 98.0% (95% CI 94.9, 99.4) in the Infanrix-Hexa group had anti-HBs concentrations ≥10 mIU/ml (primary endpoint). In a post hoc analysis, most children with pre-challenge anti-HBs concentration <10 mIU/ml achieved anti-HBs concentrations ≥10 mIU/ml (Hexavac group, 85.3% [95% CI 77.6, 91.2]; Infanrix-Hexa group, 91.9% [95% CI 78.1, 98.3]). Both challenge vaccines were well tolerated. These data suggest that immune memory persists for long-term (5 years) after a primary vaccination in infancy with a hexavalent vaccine (Hexavac or Infanrix-Hexa). Copyright © 2012 Elsevier Ltd. All rights reserved.

Seroprotection against Vaccine-Preventable Diseases amongst Health Care Workers in a Community Hospital, Qatar.

PubMed

Guanche Garcell, H; Villanueva Arias, A; Guilarte García, E; Alfonso Serrano, R N

2016-10-01

Health care workers (HCW) are at high risk of contracting various infectious diseases and play a dual role in the transmission of infections in health care facilities. To determine the seroprotection against hepatitis B, measles, rubella, and varicella among HCWs in a community hospital in Qatar. This is a cross-sectional survey conducted in a 75-bed community hospital in Dukhan, Qatar. From August 2012 to December 2015, 705 HCWs were tested for the presence of IgG antibodies for measles, rubella, and varicella, and also for hepatitis B surface antigen (HBsAg). They were also asked about previous history of hepatitis B vaccination. 595 (84.4%) HCWs received a full hepatitis B vaccination schedule; 110 (15.6%) received a single dose. The full schedule was reported with higher frequency by nurses (90.2%) compared to physicians (74.1%) or technicians (79.7%). Those aged ≥30 years (90.4%) and <20 years of work experience had received a full vaccination schedule more frequently than younger and less experienced HCWs. Female HCWs (87.8%) received full schedule more frequently than males (78.8%). 73.4% of the staff had seroprotection against heaptitis B, with the lowest anti-HBsAg titers observed in physicians (58.8%) compared with other categories; males (64.9%) were less protected than females. The seropositivity was 85.6%(95% CI 82.4% to 88.4%) for measles, 94.7% (95% CI 92.2% to 97.3%) for rubella, and 92.2% (95% CI 89.7% to 94.7%) for varicella. HCWs, particularly physicians, are not enough protected against hepatitis B. The seroprotection against measles, rubella, and varicella.

Exploring Covalent Allosteric Inhibition of Antigen 85C from Mycobacterium tuberculosis by Ebselen Derivatives

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

Goins, Christopher M.; Dajnowicz, Steven; Thanna, Sandeep

Previous studies identified ebselen as a potent in vitro and in vivo inhibitor of the Mycobacterium tuberculosis ( Mtb) antigen 85 (Ag85) complex, comprising three homologous enzymes required for the biosynthesis of the mycobacterial cell wall. In this study, the Mtb Ag85C enzyme was cocrystallized with azido and adamantyl ebselen derivatives, resulting in two crystallographic structures of 2.01 and 1.30 Å resolution, respectively. Both structures displayed the anticipated covalent modification of the solvent accessible, noncatalytic Cys209 residue forming a selenenylsulfide bond. Continuous difference density for both thiol modifiers allowed for the assessment of interactions that influence ebselen binding and inhibitormore » orientation that were unobserved in previous Ag85C ebselen structures. The k inact/ K I values for ebselen, adamantyl ebselen, and azido ebselen support the importance of observed constructive chemical interactions with Arg239 for increased in vitro efficacy toward Ag85C. To better understand the in vitro kinetic properties of these ebselen derivatives, the energetics of specific protein–inhibitor interactions and relative reaction free energies were calculated for ebselen and both derivatives using density functional theory. These studies further support the different in vitro properties of ebselen and two select ebselen derivatives from our previously published ebselen library with respect to kinetics and protein–inhibitor interactions. In both structures, the α9 helix was displaced farther from the enzyme active site than the previous Ag85C ebselen structure, resulting in the restructuring of a connecting loop and imparting a conformational change to residues believed to play a role in substrate binding specific to Ag85C. These notable structural changes directly affect protein stability, reducing the overall melting temperature by up to 14.5 °C, resulting in the unfolding of protein at physiological temperatures. Additionally

Exploring Covalent Allosteric Inhibition of Antigen 85C from Mycobacterium tuberculosis by Ebselen Derivatives

DOE PAGES

Goins, Christopher M.; Dajnowicz, Steven; Thanna, Sandeep; ...

2017-03-13

Previous studies identified ebselen as a potent in vitro and in vivo inhibitor of the Mycobacterium tuberculosis ( Mtb) antigen 85 (Ag85) complex, comprising three homologous enzymes required for the biosynthesis of the mycobacterial cell wall. In this study, the Mtb Ag85C enzyme was cocrystallized with azido and adamantyl ebselen derivatives, resulting in two crystallographic structures of 2.01 and 1.30 Å resolution, respectively. Both structures displayed the anticipated covalent modification of the solvent accessible, noncatalytic Cys209 residue forming a selenenylsulfide bond. Continuous difference density for both thiol modifiers allowed for the assessment of interactions that influence ebselen binding and inhibitormore » orientation that were unobserved in previous Ag85C ebselen structures. The k inact/ K I values for ebselen, adamantyl ebselen, and azido ebselen support the importance of observed constructive chemical interactions with Arg239 for increased in vitro efficacy toward Ag85C. To better understand the in vitro kinetic properties of these ebselen derivatives, the energetics of specific protein–inhibitor interactions and relative reaction free energies were calculated for ebselen and both derivatives using density functional theory. These studies further support the different in vitro properties of ebselen and two select ebselen derivatives from our previously published ebselen library with respect to kinetics and protein–inhibitor interactions. In both structures, the α9 helix was displaced farther from the enzyme active site than the previous Ag85C ebselen structure, resulting in the restructuring of a connecting loop and imparting a conformational change to residues believed to play a role in substrate binding specific to Ag85C. These notable structural changes directly affect protein stability, reducing the overall melting temperature by up to 14.5 °C, resulting in the unfolding of protein at physiological temperatures. Additionally

Exploring Covalent Allosteric Inhibition of Antigen 85C from Mycobacterium tuberculosis by Ebselen Derivatives.

PubMed

Goins, Christopher M; Dajnowicz, Steven; Thanna, Sandeep; Sucheck, Steven J; Parks, Jerry M; Ronning, Donald R

2017-05-12

Previous studies identified ebselen as a potent in vitro and in vivo inhibitor of the Mycobacterium tuberculosis (Mtb) antigen 85 (Ag85) complex, comprising three homologous enzymes required for the biosynthesis of the mycobacterial cell wall. In this study, the Mtb Ag85C enzyme was cocrystallized with azido and adamantyl ebselen derivatives, resulting in two crystallographic structures of 2.01 and 1.30 Å resolution, respectively. Both structures displayed the anticipated covalent modification of the solvent accessible, noncatalytic Cys209 residue forming a selenenylsulfide bond. Continuous difference density for both thiol modifiers allowed for the assessment of interactions that influence ebselen binding and inhibitor orientation that were unobserved in previous Ag85C ebselen structures. The k inact /K I values for ebselen, adamantyl ebselen, and azido ebselen support the importance of observed constructive chemical interactions with Arg239 for increased in vitro efficacy toward Ag85C. To better understand the in vitro kinetic properties of these ebselen derivatives, the energetics of specific protein-inhibitor interactions and relative reaction free energies were calculated for ebselen and both derivatives using density functional theory. These studies further support the different in vitro properties of ebselen and two select ebselen derivatives from our previously published ebselen library with respect to kinetics and protein-inhibitor interactions. In both structures, the α9 helix was displaced farther from the enzyme active site than the previous Ag85C ebselen structure, resulting in the restructuring of a connecting loop and imparting a conformational change to residues believed to play a role in substrate binding specific to Ag85C. These notable structural changes directly affect protein stability, reducing the overall melting temperature by up to 14.5 °C, resulting in the unfolding of protein at physiological temperatures. Additionally, this structural

Nanocomposite of exfoliated bentonite/g-C3N4/Ag3PO4 for enhanced visible-light photocatalytic decomposition of Rhodamine B.

PubMed

Ma, Jianfeng; Huang, Daiqin; Zhang, Wenyi; Zou, Jing; Kong, Yong; Zhu, Jianxi; Komarneni, Sridhar

2016-11-01

Novel visible-light-driven heterojunction photocatalyst comprising exfoliated bentonite, g-C3N4 and Ag3PO4 (EB/g-C3N4/Ag3PO4) was synthesized by a facile and green method. The composites EB/g-C3N4/Ag3PO4 were characterized by X-ray diffraction, Transmission electron microscopy, Fourier transform infrared spectroscopy, UV-Vis diffuse reflectance spectroscopy and the Brunauer, Emmett, and Teller (BET) surface area method. Under visible light irradiation, EB/g-C3N4/Ag3PO4 composites displayed much higher photocatalytic activity than that of either pure g-C3N4 or pure Ag3PO4 in the degradation of Rhodamine B (RhB). Among the hybrid photocatalysts, EB/g-C3N4/Ag3PO4 composite containing 20 wt% Ag3PO4 exhibited the highest photocatalytic activity for the decolorization of RhB. Under the visible-light irradiation, the RhB dye was completely decolorized in less than 60 min. The enhanced photocatalytic performance is attributed to the stable structure, enlarged surface area, strong adsorbability, strong light absorption ability, and high-efficiency separation rate of photoinduced electron-hole pairs. Our finding paves a way to design highly efficient and stable visible-light-induced photocatalysts for practical applications in wastewater treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

The status of hepatitis B control in the African region

PubMed Central

Breakwell, Lucy; Tevi-Benissan, Carol; Childs, Lana; Mihigo, Richard; Tohme, Rania

2017-01-01

The World Health Organization (WHO) African Region has approximately 100 million people with chronic hepatitis B virus (HBV) infection. This review describes the status of hepatitis B control in the Region. We present hepatitis B vaccine (HepB) coverage data and from available data in the published literature, the impact of HepB vaccination on hepatitis B surface antigen (HBsAg) prevalence, a marker of chronic infection, among children, HBsAg prevalence in pregnant women, and risk of perinatal transmission. Lastly, we describe challenges with HepB birth dose (HepB-BD) introduction reported in the Region, and propose strategies to increase coverage. In 2015, regional three dose HepB coverage was 76%, and 16(34%) of 47 countries reported ≥ 90% coverage. Overall, 11 countries introduced HepB-BD; only nine provide universal HepB-BD, and of these, five reported ≥ 80% coverage. From non-nationally representative serosurveys among children, HBsAg prevalence was lower among children born after HepB introduction compared to those born before HepB introduction. However, some studies still found HBsAg prevalence to be above 2%. From limited surveys among pregnant women, the median HBsAg prevalence varied by country, ranging from 1.9% (Madagascar) to 16.1% (Niger); hepatitis B e antigen (HBeAg) prevalence among HBsAg-positive women ranged from 3.3% (Zimbabwe) to 28.5% (Nigeria). Studies in three countries indicated that the risk of perinatal HBV transmission was associated with HBeAg expression or high HBV DNA viral load. Major challenges for timely HepB-BD administration were poor knowledge of or lack of national HepB-BD vaccination guidelines, high prevalence of home births, and unreliable vaccine supply. Overall, substantial progress has been made in the region. However, countries need to improve HepB3 coverage and some countries might need to consider introducing the HepB-BD to help achieve the regional hepatitis B control goal of < 2% HBsAg prevalence among children

Immunogenicity of Sci-B-Vac (a Third-Generation Hepatitis B Vaccine) in HIV-Positive Adults.

PubMed

Alon, Danny; Stein, Gideon Y; Hadas-Golan, Vered; Tau, Luba; Brosh, Tal; Turner, Dan

2017-03-01

Guidelines recommend hepatitis B virus (HBV) vaccination of all adults positive for human immunodeficiency virus (HIV). Immune responses to single-antigen HBV vaccine among HIV-positive patients are low when compared with HIV-negative adults. Sci-B-Vac™ is a recombinant third-generation HBV that may be advantageous in this population. To examine the immune responses to Sci-B-Vac among HIV-positive adults. We conducted a prospective cohort study involving HIV-positive adults who had negative HBV serology (HBSAg, HBSAb, HBcoreAb). Sci-B-Vac at 10 µg/dose was administered intramuscularly upon recruitment and after 1 and 6 months. HBSAb levels were checked 1 month after each dose; a level > 10 mlU/ml was considered protective. Data regarding age, gender, CD4 level, and viral load were collected. The study group comprised 31 patients. Average CD4 count was 503 ± 281 cells/ml, and average viral load was 44 copies/ml. Median interquartile range (IQR) HBVAb titers after the first, second and third immunizations were 0 (0, 3.5), 30 (6, 126) and 253 (81, 408) mlU/ml. Significant titer elevations were found between the second and third immunizations (P = 0.0003). The rate of patients considered protected was 16% after the first, 65% after the second (P < 0.0001), and 84% after the third dose (P = 0.045). No adverse events were reported. More patients under the age of 40 years responded to the first immunization (28% vs. 0%, P = 0.038). CD4 level had no influence on immunization rates. Sci-B-Vac might achieve better immunization rates among HIV-positive adults compared to the single-antigen vaccine and thus deserves further evaluation in a randomized, double-blind study in this population.

Hepatitis B vaccine - what you need to know

MedlinePlus

... is taken in its entirety from the CDC Hepatitis B Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... statements/hep-b.html CDC review information for Hepatitis B VIS: Page last reviewed: July 20, 2016 Page ...

The effects of different dosage levels of hepatitis B vaccine as booster on anti-HBs-negative children 5-15 y after primary immunization; China, 2009-2010.

PubMed

Chen, Yongdi; Lv, Huakun; Gu, Hua; Cui, Fujiang; Wang, Fuzhen; Yao, Jun; Xia, Shichang; Liang, Xiaofeng

2014-01-01

The changes in lgG antibody levels to hepatitis B surface antigen (HBsAg) and in antibody to HBsAg (anti-HBs) seroconversion rates due to different dosages of hepatitis B vaccine (HepB) were compared in 2106 children. Children who had been previously vaccinated as infants with HepB were revaccinated at 5-15 y of age, after which the antibody titers were determined. After the first booster dose, the anti-HBs seroconversion rate (defined as an anti-HBs ≥10 mIU/ml) with 10 μg of HepB (93.6%) was significantly greater than the rate with 5 µg of HepB (90.3%) (P<0.05); the anti-HBs seroconversion rate in 10-15-y-old boys vaccinated with 10 μg of HepB (90.9%) was significantly greater than the rate with 5 µg of HepB (84.3%) (P<0.05). The anti-HBs seroconversion rates after the third booster dose with 5 or 10 μg of HepB were greater than those after the first booster dose (99.6% and 99.7%, vs. 90.3% and 93.6%, P<0.05); as was the corresponding GMTs (658 ± 4 mIU/ml and 2599 ± 3 mIU/ml, vs. 255 ± 11 mIU/ml and 877 ± 11 mIU/ml [P<0.05]). The immunization effects of booster vaccination with 3 doses of HepB with 5 or 10 µg are effective; a single booster dose with 10 µg of HepB for 10-15-y-old boys and with 5 or 10 µg of HepB for 5-9 y old boys and for 5-15-y-old girls are effective in generating protective antibody against HBV; however, for anti-HBs-negative children after a single dose of booster, 3 doses are needed.

Targeting Mycobacterium tuberculosis Antigens to Dendritic Cells via the DC-Specific-ICAM3-Grabbing-Nonintegrin Receptor Induces Strong T-Helper 1 Immune Responses

PubMed Central

Velasquez, Lis Noelia; Stüve, Philipp; Gentilini, Maria Virginia; Swallow, Maxine; Bartel, Judith; Lycke, Nils Yngve; Barkan, Daniel; Martina, Mariana; Lujan, Hugo D.; Kalay, Hakan; van Kooyk, Yvette; Sparwasser, Tim D.; Berod, Luciana

2018-01-01

Tuberculosis remains a major global health problem and efforts to develop a more effective vaccine have been unsuccessful so far. Targeting antigens (Ags) to dendritic cells (DCs) in vivo has emerged as a new promising vaccine strategy. In this approach, Ags are delivered directly to DCs via antibodies that bind to endocytic cell-surface receptors. Here, we explored DC-specific-ICAM3-grabbing-nonintegrin (DC-SIGN) targeting as a potential vaccine against tuberculosis. For this, we made use of the hSIGN mouse model that expresses human DC-SIGN under the control of the murine CD11c promoter. We show that in vitro and in vivo delivery of anti-DC-SIGN antibodies conjugated to Ag85B and peptide 25 of Ag85B in combination with anti-CD40, the fungal cell wall component zymosan, and the cholera toxin-derived fusion protein CTA1-DD induces strong Ag-specific CD4+ T-cell responses. Improved anti-mycobacterial immunity was accompanied by increased frequencies of Ag-specific IFN-γ+ IL-2+ TNF-α+ polyfunctional CD4+ T cells in vaccinated mice compared with controls. Taken together, in this study we provide the proof of concept that the human DC-SIGN receptor can be efficiently exploited for vaccine purposes to promote immunity against mycobacterial infections. PMID:29662482

Immunogenicity of transgenic plant-derived hepatitis B surface antigen.

PubMed Central

Thanavala, Y; Yang, Y F; Lyons, P; Mason, H S; Arntzen, C

1995-01-01

The focus of the Children's Vaccine Initiative is to encourage the discovery of technology that will make vaccines more readily available to developing countries. Our strategy has been to genetically engineer plants so that they can be used as inexpensive alternatives to fermentation systems for production of subunit antigens. In this paper we report on the immunological response elicited in vivo by using recombinant hepatitis B surface antigen (rHBsAg) purified from transgenic tobacco leaves. The anti-hepatitis B response to the tobacco-derived rHBsAg was qualitatively similar to that obtained by immunizing mice with yeast-derived rHBsAg (commercial vaccine). Additionally, T cells obtained from mice primed with the tobacco-derived rHBsAg could be stimulated in vitro by the tobacco-derived rHBsAg, yeast-derived rHBsAg, and by a synthetic peptide that represents part of the a determinant located in the S region (139-147) of HBsAg. Further support for the integrity of the T-cell epitope of the tobacco-derived rHBsAg was obtained by testing the ability of the primed T cells to proliferate in vitro after stimulation with a monoclonal anti-idiotype and an anti-idiotype-derived peptide, both of which mimic the group-specific a determinant of HBsAg. In total, we have conclusively demonstrated that both B- and T-cell epitopes of HBsAg are preserved when the antigen is expressed in a transgenic plant. PMID:7724566

Meningococcal B Vaccination (4CMenB) in Infants and Toddlers

PubMed Central

Esposito, Susanna; Tagliabue, Claudia; Bosis, Samantha

2015-01-01

Neisseria meningitidis is a Gram-negative pathogen that actively invades its human host and leads to the development of life-threatening pathologies. One of the leading causes of death in the world, N. meningitidis can be responsible for nearly 1,000 new infections per 100,000 subjects during an epidemic period. The bacterial species are classified into 12 serogroups, five of which (A, B, C, W, and Y) cause the majority of meningitides. The three purified protein conjugate vaccines currently available target serogroups A, C, W, and Y. Serogroup B has long been a challenge but the discovery of the complete genome sequence of an MenB strain has allowed the development of a specific four-component vaccine (4CMenB). This review describes the pathogenetic role of N. meningitidis and the recent literature concerning the new meningococcal vaccine. PMID:26351647

Meningococcal B vaccination: real-world experience and future perspectives

PubMed Central

Kuhdari, Parvanè; Valente, Nicoletta; Gabutti, Giovanni

2016-01-01

Invasive meningococcal disease (IMD) represents a severe risk for health. It can be considered the most dangerous vaccine-preventable disease due to the high probability of related permanent sequelae and death. The introduction in many countries of the conjugate vaccines against A, C, W135, and Y meningococcal serogroups influenced significantly the impact of the disease. Recently, the difficulties in obtaining an effective vaccine against meningococcal serogroup B (MenB) have been get over through the reverse vaccinology, enabling the recognition of some antigens providing a response against most of circulating MenB strains worldwide. The new 4cMenB vaccine is recommended in Europe, Canada, Australia, the USA, and some Latin American countries. Even if sound data on efficacy and safety profile are available, the results in terms of effectiveness are still limited. The management of the MenB outbreaks in two US universities demonstrated the ability to quickly achieve high vaccination coverage rates and no new cases among immunized subjects were assessed. It is desirable that the opportunity to complete preventive intervention against IMD offered by the new 4cMenB vaccine should be recognized and that this vaccine is included in the vaccination schedule to complete the panel of immunization against Neisseria meningitidis. PMID:27309042

Old and new adjuvants for hepatitis B vaccines.

PubMed

Leroux-Roels, Geert

2015-02-01

The safety and immunogenicity profiles of currently available recombinant hepatitis B vaccines are excellent. However, it remains a real challenge to induce protective immunity in the target groups that respond poorly or not at all to conventional vaccines. Ideally, a hepatitis B vaccine can be developed that conveys lifelong protection against infection rapidly after the injection of a single dose. Although this goal is far from being reached, important improvements have been made. Novel vaccine adjuvants have been developed that enhance the immunogenicity of recombinant hepatitis B vaccines while maintaining a good safety profile. The different adjuvants and adjuvant systems that are discussed herein have all been thoroughly evaluated in clinical trials and some have reached or are close to reach the market.

Excellent response rate to a double dose of the combined hepatitis A and B vaccine in previous nonresponders to hepatitis B vaccine.

PubMed

Cardell, Kristina; Akerlind, Britt; Sällberg, Matti; Frydén, Aril

2008-08-01

Hepatitis B vaccine has been shown to be highly efficient in preventing hepatitis B. However, 5%-10% of individuals fail to develop protective levels (>or=10 mIU/mL) of antibodies to hepatitis B surface antigen (anti-HBs) and are considered to be nonresponders. A total of 48 nonresponders and 20 subjects naive to the HBV vaccine received a double dose of combined hepatitis A and B vaccine (Twinrix) at 0, 1, and 6 months. The levels of anti-HBs and antibodies to hepatitis A virus (anti-HAV) were determined before vaccination and 1 month after each dose. Among 44 nonresponders, protective anti-HBs levels were found in 26 (59%) after the first dose and in 42 (95%) after the third dose. Among the control subjects, the corresponding figures were 10% and 100%, respectively. All subjects seroconverted to anti-HAV. The titers of both anti-HBs and anti-HAV were lower in the previously nonresponsive subjects (P< .01). Revaccination of nonresponders to the standard hepatitis B vaccine regimen with a double dose of the combined hepatitis A and B vaccine was highly effective. This is most likely explained by the increased dose, a positive bystander effect conferred by the hepatitis A vaccine, or both.

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.

HBeAg and hepatitis B virus DNA as outcome predictors during therapy with peginterferon alfa-2a for HBeAg-positive chronic hepatitis B.

PubMed

Fried, Michael W; Piratvisuth, Teerha; Lau, George K K; Marcellin, Patrick; Chow, Wan-Cheng; Cooksley, Graham; Luo, Kang-Xian; Paik, Seung Woon; Liaw, Yun-Fan; Button, Peter; Popescu, Matei

2008-02-01

The aims of this study were to evaluate the usefulness of quantitative hepatitis B e antigen (HBeAg) values for predicting HBeAg seroconversion in patients treated with peginterferon alfa-2a and to assess the dynamic changes in quantitative HBeAg during therapy, compared with conventional measures of serum hepatitis B virus DNA. Data were analyzed from a large, randomized, multinational phase III registration trial involving 271 HBV-infected HBeAg-positive patients who received peginterferon alfa-2a plus oral placebo for 48 weeks. HBeAg levels were measured serially during therapy using a microparticle enzyme immunoassay validated with in-house reference standards obtained from the Paul Ehrlich Institute (PEIU/mL). In patients who achieved HBeAg seroconversion, levels of HBeAg consistently decreased during treatment and remained at their lowest level during the 24 weeks of posttreatment follow-up. After 24 weeks of treatment, 4% of patients with the highest levels of HBeAg (>or=100 PEIU/mL) achieved HBeAg seroconversion, yielding a negative predictive value of 96%, which was greater than that obtained for levels of HBV DNA (86%). Late responders to peginterferon alfa-2a could also be differentiated from nonresponders by continued decrease in HBeAg values, which were not evident by changes in HBV DNA. These analyses suggest quantitative HBeAg is a useful adjunctive measurement for predicting HBeAg seroconversion in patients treated with peginterferon when considering both sensitivity and specificity compared with serum HBV DNA.

Detection of hepatitis B virus (HBV) genotype E carried--even in the presence of high titers of anti-HBs antibodies--by an Argentinean patient of African descent who had received vaccination against HBV.

PubMed

Mathet, Verónica L; Cuestas, María L; Ruiz, Vanesa; Minassian, María L; Rivero, Cintia; Trinks, Julieta; Daleoso, Graciela; León, Liliana M; Sala, Andrea; Libellara, Beatriz; Corach, Daniel; Oubiña, José R

2006-09-01

Genotype E hepatitis B virus (HBV) was detected in two Argentine sisters exhibiting an African mitochondrial lineage. One of them (who had been vaccinated against HBV) exhibited anti-HBs cocirculating antibodies without HBsAg escape mutants, while her unvaccinated sister showed a D144A HBsAg escape mutant without anti-HBs antibodies. Both sisters carried an unusual L209V substitution within HBsAg.

Immunomodulation therapy in children with chronic hepatitis B.

PubMed Central

Karaoglan, Murat; Demirci, Fikret; Coskun, Yavuz; Karaoglan, Ilkay; Bayraktaroglu, Ziya; Okan, Vahap; Karsligil, Tekin

2006-01-01

PURPOSE: The aim of this study is to investigate the effects of HBsAg vaccine and levamisole on virological indicators in naive patients suffering from chronic hepatitis B (CHB) and in healthy carriers of hepatitis B. METHOD: Vaccination and treatment with levamisole were applied to 93 minor patients in total, 43 of them inactive CHB carriers and 50 patients suffering from CHB. RESULTS: 15 (30%) of 50 patients who had high ALT values in the beginning of the study had normal values after treatment. In nine (12%) patients, posttreatment ALT values were higher than pretreatment values, and six (10%) patients showed HBV-DNA loss. In spite of the presence of 50 (54%) HBeAg-positive patients before treatment, 17 (34%) patients proved to be HBeAg-negative after treatment. HBeAg sero-conversion was seen in 10 (20%) cases. In two (2%) patients, HBsAg sero-conversion occurred. CONCLUSION: It was found that treatment with levamisole and vaccine had positive effects on CHB patients and healthy carriers with respect to HBV DNA loss, HBeAg sero-conversion and ALT normalization. The viral load increases and ALT increases that occurred in certain cases were thought to be related to the early immune response. It was determined that combined levamisole and vaccine therapy had no additional positive effect. PMID:16708498

Long-term T-cell-mediated immunologic memory to hepatitis B vaccine in young adults following neonatal vaccination.

PubMed

Saffar, Hiva; Saffar, Mohammed Jafar; Ajami, Abolghasem; Khalilian, Ali Reza; Shams-Esfandabad, Kian; Mirabi, Araz Mohammad

2014-09-01

The long-term duration of cell-mediated immunity induced by neonatal hepatitis B virus (HBV) vaccination is unknown. Study was designed to determine the cellular immunity memory status among young adults twenty years after infantile HB immunization. Study subjects were party selected from a recent seroepidemiologic study in young adults, who had been vaccinated against HBV twenty years earlier. Just before and ten to 14 days after one dose of HBV vaccine booster injection, blood samples were obtained and sera concentration of cytokines (interleukin 2 and interferon) was measured. More than twofold increase after boosting was considered positive immune response. With regard to the serum level of antibody against HBV surface antigen (HBsAb) before boosting, the subjects were divided into four groups as follow: GI, HBsAb titer < 2; GII, titer 2 to 9.9; GIII, titer 10 to 99; and GIV, titers ≥ 100 IU/L. Mean concentration level (MCL) of each cytokines for each group at preboosting and postboosting and the proportion of responders in each groups were determined. Paired descriptive statistical analysis method (t test) was used to compare the MCL of each cytokines in each and between groups and the frequency of responders in each group. Before boosting, among 176 boosted individuals, 75 (42.6%) had HBsAb 10 IU/L and were considered seroprotected. Among 101 serosusceptible persons, more than 80% of boosted individuals showed more than twofold increase in cytokines concentration, which meant positive HBsAg-specific cell-mediated immunity. MCL of both cytokines after boosting in GIV were decreased more than twofold, possibly because of recent natural boosting. Findings showed that neonatal HBV immunization was efficacious in inducing long-term immunity and cell-mediated immune memory for up to two decades, and booster vaccination are not required. Further monitoring of vaccinated subjects for HBV infections are recommended.

Vaccination uptake and awareness of a free hepatitis B vaccination program among female commercial sex workers.

PubMed

Baars, Jessica E; Boon, Brigitte J F; Garretsen, Henk F; van de Mheen, Dike

2009-01-01

We sought to explore the reach of a free hepatitis B vaccination program among female commercial sex workers (CSWs) within a legalized prostitution setting in the Netherlands. We also investigated the reasons for nonparticipation and noncompliance. In this cross-sectional study based on ethnographic mapping and targeted sampling, 259 CSWs were interviewed at their work in 3 regions in the Netherlands. The semistructured interviews contained questions on sociodemographics, sexual risk behavior, sex work, awareness of the opportunity to obtain free hepatitis B vaccination, vaccination uptake, and compliance with the full vaccination schedule. Of our sample, 79% reported awareness of the opportunity to obtain hepatitis B vaccination, and 63% reported to be vaccinated against hepatitis B (received > or =1 vaccination). A personal approach by health professionals or was associated with vaccination uptake, when specific sociodemographic variables, sexual behavior, and sex work related covariates were controlled for in the analysis. Window prostitution and the duration of working in the region were associated with awareness of the opportunity to obtain free hepatitis B vaccination. The results of this study suggest that outreach activities (i.e., a personal approach) within this program are beneficial. Transient CSWs are more difficult to reach within the current vaccination program. These results can be used to increase the success of future health programs among this risk group.

Oral Vaccination with Lipid-Formulated BCG Induces a Long-lived, Multifunctional CD4+ T Cell Memory Immune Response

PubMed Central

Ancelet, Lindsay R.; Aldwell, Frank E.; Rich, Fenella J.; Kirman, Joanna R.

2012-01-01

Oral delivery of BCG in a lipid formulation (Liporale™-BCG) targets delivery of viable bacilli to the mesenteric lymph nodes and confers protection against an aerosol Mycobacterium tuberculosis challenge. The magnitude, quality and duration of the effector and memory immune response induced by Liporale™-BCG vaccination is unknown. Therefore, we compared the effector and memory CD4+ T cell response in the spleen and lungs of mice vaccinated with Liporale™-BCG to the response induced by subcutaneous BCG vaccination. Liporale™-BCG vaccination induced a long-lived CD4+ T cell response, evident by the detection of effector CD4+ T cells in the lungs and a significant increase in the number of Ag85B tetramer-specific CD4+ T cells in the spleen up to 30 weeks post vaccination. Moreover, following polyclonal stimulation, Liporale™-BCG vaccination, but not s.c. BCG vaccination, induced a significant increase in both the percentage of CD4+ T cells in the lungs capable of producing IFNγ and the number of multifunctional CD4+ T cells in the lungs at 30 weeks post vaccination. These results demonstrate that orally delivered Liporale™-BCG vaccine induces a long-lived multifunctional immune response, and could therefore represent a practical and effective means of delivering novel BCG-based TB vaccines. PMID:23049885

Enteric trimethyl chitosan nanoparticles containing hepatitis B surface antigen for oral delivery.

PubMed

Farhadian, Asma; Dounighi, Naser Mohammadpour; Avadi, Mohammadreza

2015-01-01

Oral vaccination is the preferred route of immunization. However, the degradative condition of the gastrointestinal tract and the higher molecular size of peptides pose major challenges in developing an effective oral vaccination system. One of the most excellent methods used in the development of oral vaccine delivery system relies on the entrapment of the antigen in polymeric nanoparticles. In this work, trimethyl chitosan (TMC) nanoparticles were fabricated using ionic gelation teqnique by interaction hydroxypropyl methylcellulose phthalate (HPMCP), a pH-sensitive polymer, with TMC and the utility of the particles in the oral delivery of hepatitis B surface antigen (HBsAg) was evaluated employing solutions that simulated gastric and intestinal conditions. The particle size, morphology, zeta potential, loading capacity, loading efficiency, in vitro release behavior, structure, and morphology of nanoparticles were evaluated, and the activity of the loaded antigen was assessed. Size of the optimized TMC/HPMCP nanoparticles and that of the antigen-loaded nanoparticles were 85 nm and 158 nm, respectively. Optimum loading capacity (76.75%) and loading efficiency (86.29%) were achieved at 300 µg/mL concentration of the antigen. SEM images revealed a spherical shape as well as a smooth and near-homogenous surface of nanoparticles. Results of the in vitro release studies showed that formulation with HPMCP improved the acid stability of the TMC nanoparticles as well as their capability to preserve the loaded HBsAg from gastric destruction. The antigen showed good activity both before and after loading. The results suggest that TMC/HPMCP nanoparticles could be used in the oral delivery of HBsAg vaccine.

Hepatitis A, B, and A/B vaccination series completion among US adults: a claims-based analysis.

PubMed

Ghaswalla, Parinaz K; Patterson, Brandon J; Cheng, Wendy Y; Duchesneau, Emilie; Macheca, Monica; Duh, Mei Sheng

2018-06-20

Hepatitis A and B disease burden persists in the US. We assessed hepatitis A and hepatitis B vaccination series completion rates among 350,240 commercial/Medicare and 12,599 Medicaid enrollees aged ≥19 years. A vaccination series was considered as completed provided that the minimum interval between doses, as defined by the CDC, and the minimum number of doses were reached. We stratified completion rates by vaccine type (i.e. monovalent or bivalent) at initial vaccination for each cohort. In the commercial/Medicare cohort, the series completion rate was 32.0% for hepatitis A and 39.6% for hepatitis B among those who initiated with a monovalent vaccine, and it was 36.2% for hepatitis A and 48.9% for hepatitis B among those who initiated with a bivalent vaccine. In the Medicaid cohort, the series completion rate was 21.0% for hepatitis A and 24.0% for hepatitis B among those who initiated with a monovalent vaccine, and it was 19.0% for hepatitis A and 24.6% for hepatitis B among those who initiated with a bivalent vaccine. In conclusion, hepatitis A and B vaccination series completion rates were low, and appeared to be lower among Medicaid than among commercial/Medicare enrollees. Commercial/Medicare enrollees who initiated with a bivalent vaccine had higher series completion rates than those who initiated with monovalent vaccines - an observation that was not made among Medicaid enrollees.

Surface antibody and cytokine response to recombinant Chinese hamster ovary cell (CHO) hepatitis B vaccine.

PubMed

Zhang, Wei; Han, Lili; Lin, Changying; Wang, Huai; Pang, Xinghuo; Li, Liqiu; Gao, Pei; Lin, Hui; Gong, Xiaohong; Tang, Yaqing; Ma, Jianxin; Zhang, Haiyan; Wang, Chen; Yang, Peng; Li, Hui; Sun, Meiping; He, Xiong

2011-08-26

To compare the immune responses of the 10 μg and 20 μg doses of CHO hepatitis B vaccine on adults. Adults aged 18-45 years who gave a history of never having received hepatitis B vaccine and lacked serologic evidence of infection to hepatitis B virus (HBV) infection or previous vaccination were enrolled into the study. A total of 642 eligible participants were randomized to receive 3 doses of either the 10 μg or the 20 μg formulation of CHO hepatitis B vaccine in a 0-1-6 month schedule. Each study subject had a serologic specimen collected one month following the third vaccine dose that was tested for markers of HBV infection and anti-HBs by Abbott I2000. Persons who tested negative for anti-HBs negative persons were tested for HBV DNA. Logistic regression was used to identify factors associated with antibody response. Among the participants, 153 subjects had their lymphocytes cultivated and tested for cytokine production. Enzyme-linked immunospot (ELISPOT) was used to test spot numbers of IL-4, IFN-γ which produced by lymphocyte. The anti-HBs seroconversion rate was 88.8% (95% CI: 85.4-92.2%) and 95.3% (95% CI: 93.0-97.6%), respectively in 10 μg and 20 μg group. Geometric mean titers (GMT) were 173.42 mIU/ml and 585.51 mIU/ml, respectively in 10 μg and 20 μg groups. Multivariate analysis demonstrated that diabetes, spouse is hepatitis B virus infector, older age and receipt of the 10 μg dose were all negatively associated with antibody response (P<.05). Cellular immunity results showed: IL-4 immunity spot numbers in 20 μg group was higher than 10 μg group. With anti-HBs increased, the IL-4 immunity spot numbers increased significantly which had significant positive correlation (Spearman coefficient=0.538, P<0.0001). IFN-γ spot numbers had no statistical significant between the two groups. The humoral immunity and cytokines response among the group that received the 20 μg CHO hepatitis B vaccine dose was superior compared to the group that received

Characterization of the size distribution and aggregation of virus-like nanoparticles used as active ingredients of the HeberNasvac therapeutic vaccine against chronic hepatitis B

NASA Astrophysics Data System (ADS)

Lopez, Matilde; Rodriguez, Elias Nelson; Lobaina, Yadira; Musacchio, Alexis; Falcon, Viviana; Guillen, Gerardo; Aguilar, Julio C.

2017-06-01

The use of virus-like particles (VLPs) as antigens constitutes a well established strategy in preventive vaccination. These non-infective particles have a composition, size, and structure favoring their interaction and processing by the immune system. Recombinant viral nucleocapsids encapsulating bacterial nucleic acids result in potent Th1-driving immunogens. Several antigens have been coadministered with VLPs or conjugated to them to further increase their immunogenicity. In the present work we characterize the size distribution of two different recombinant VLPs obtained as components of HeberNasvac, a novel therapeutic vaccine recently registered to treat chronic hepatitis B. The vaccine ingredients, hepatitis B virus surface and nucleocapsid antigens (HBsAg and HBcAg, respectively) and the vaccine formulation, were evaluated using dynamic light scattering (DLS), transmission electron microscopy (TEM) and light obscuration technology. The results demonstrate that both antigens are nanoparticles with sizes ranging between 20-30 nm, in line with reports in the literature. In addition, DLS studies evidenced the capacity of both antigens to form homologous and heterologous aggregates, both as active ingredients as well as being part of the final product. The evaluation of subvisible particles in HeberNasvac formulation fulfills the requirements in terms of quantity and size established for parenteral pharmaceutical compositions. Invited talk at 8th Int. Workshop on Advanced Materials Science and Nanotechnology (IWAMSN2016) (Ha Long City, Vietnam, 8-12 November 2016)

The new silver borate Ag{sub 3}B{sub 5}O{sub 9}

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

Sohr, Gerhard; Falkowski, Viktoria; Huppertz, Hubert, E-mail: hubert.huppertz@uibk.ac.at

2015-05-15

Single crystals of Ag{sub 3}B{sub 5}O{sub 9} were obtained via high-pressure synthesis at 3 GPa and 600 °C, using a Walker-type multianvil high-pressure device. Ag{sub 3}B{sub 5}O{sub 9} crystalizes with a=674.7(2), b=943.5(2), c=1103.5(2) pm, V=0.7025(2) nm{sup 3}, and Z=4 in the noncentrosymmetric space group P2{sub 1}2{sub 1}2{sub 1} (no. 19). The orthorhombic structure was refined from 3740 independent reflections with R1=0.0496 and wR2=0.587 (all data). It is built up from infinite corner-sharing chains of BO{sub 4} tetrahedra along the a axis, which are interconnected by BO{sub 3} groups to form a network. In the structure, three crystallographically independent sites aremore » occupied with Ag{sup +} cations exhibiting argentophillic interactions. The synthetic conditions as well as the results of the single crystal structure analysis are presented. - Graphical abstract: Noncentrosymmetric silver borate: During investigations in the system Ag–B–O, a new noncentrosymmetric silver borate Ag{sub 3}B{sub 5}O{sub 9} was discovered. The new structure type is built up from corner-sharing BO{sub 3} and BO{sub 4} groups, forming a network. Argentophillic interactions are clearly indicated by the Ag{sup +}⋯Ag{sup +} distances present in the structure. - Highlights: • A noncentrosymmetric borate Ag{sub 3}B{sub 5}O{sub 9} is accessible via high-pressure synthesis. • Ag{sub 3}B{sub 5}O{sub 9} is the second high-pressure silver borate. • Ag{sup +}⋯Ag{sup +} distances in Ag3B5O9 clearly indicate the presence of argentophillic interactions.« less

Progress toward Elimination of Hepatitis B Virus Transmission in Oman: Impact of Hepatitis B Vaccination

PubMed Central

Thabit Al Awaidy, Salah; Pandurang Bawikar, Shyam; Salim Al Busaidy, Suleiman; Al Mahrouqi, Salim; Al Baqlani, Said; Al Obaidani, Idris; Alexander, James; Patel, Minal K.

2013-01-01

Approximately 2–7% of the Omani population has chronic hepatitis B virus (HBV) infection. To decrease this burden, universal childhood hepatitis B vaccination was introduced in Oman in 1990. The hepatitis B vaccination strategy and reported coverage were reviewed. To assess the impact of the program on chronic HBV seroprevalence, a nationally representative seroprevalence study was conducted in Oman in 2005. Since 1991, hepatitis B vaccination in Oman has reached almost every eligible child, with reported coverage of ≥ 97% for the birth dose and ≥ 94% for three doses. Of 175 children born pre-vaccine introduction, 16 (9.1%) had evidence of HBV exposure, and 4 (2.3%) had evidence of chronic infection. Of 1,890 children born after vaccine introduction, 43 (2.3%) had evidence of HBV exposure, and 10 (0.5%) had evidence of chronic infection. Oman has a strong infant hepatitis B vaccination program, resulting in a dramatic decrease in chronic HBV seroprevalence. PMID:23958910

Progress toward elimination of hepatitis B virus transmission in Oman: impact of hepatitis B vaccination.

PubMed

Al Awaidy, Salah Thabit; Bawikar, Shyam Pandurang; Al Busaidy, Suleiman Salim; Al Mahrouqi, Salim; Al Baqlani, Said; Al Obaidani, Idris; Alexander, James; Patel, Minal K

2013-10-01

Approximately 2-7% of the Omani population has chronic hepatitis B virus (HBV) infection. To decrease this burden, universal childhood hepatitis B vaccination was introduced in Oman in 1990. The hepatitis B vaccination strategy and reported coverage were reviewed. To assess the impact of the program on chronic HBV seroprevalence, a nationally representative seroprevalence study was conducted in Oman in 2005. Since 1991, hepatitis B vaccination in Oman has reached almost every eligible child, with reported coverage of ≥ 97% for the birth dose and ≥ 94% for three doses. Of 175 children born pre-vaccine introduction, 16 (9.1%) had evidence of HBV exposure, and 4 (2.3%) had evidence of chronic infection. Of 1,890 children born after vaccine introduction, 43 (2.3%) had evidence of HBV exposure, and 10 (0.5%) had evidence of chronic infection. Oman has a strong infant hepatitis B vaccination program, resulting in a dramatic decrease in chronic HBV seroprevalence.

Development of high-yield influenza B virus vaccine viruses

PubMed Central

Ping, Jihui; Lopes, Tiago J. S.; Neumann, Gabriele; Kawaoka, Yoshihiro

2016-01-01

The burden of human infections with influenza A and B viruses is substantial, and the impact of influenza B virus infections can exceed that of influenza A virus infections in some seasons. Over the past few decades, viruses of two influenza B virus lineages (Victoria and Yamagata) have circulated in humans, and both lineages are now represented in influenza vaccines, as recommended by the World Health Organization. Influenza B virus vaccines for humans have been available for more than half a century, yet no systematic efforts have been undertaken to develop high-yield candidates. Therefore, we screened virus libraries possessing random mutations in the six “internal” influenza B viral RNA segments [i.e., those not encoding the major viral antigens, hemagglutinin (HA) and neuraminidase NA)] for mutants that confer efficient replication. Candidate viruses that supported high yield in cell culture were tested with the HA and NA genes of eight different viruses of the Victoria and Yamagata lineages. We identified combinations of mutations that increased the titers of candidate vaccine viruses in mammalian cells used for human influenza vaccine virus propagation and in embryonated chicken eggs, the most common propagation system for influenza viruses. These influenza B virus vaccine backbones can be used for improved vaccine virus production. PMID:27930325

Development of high-yield influenza B virus vaccine viruses.

PubMed

Ping, Jihui; Lopes, Tiago J S; Neumann, Gabriele; Kawaoka, Yoshihiro

2016-12-20

The burden of human infections with influenza A and B viruses is substantial, and the impact of influenza B virus infections can exceed that of influenza A virus infections in some seasons. Over the past few decades, viruses of two influenza B virus lineages (Victoria and Yamagata) have circulated in humans, and both lineages are now represented in influenza vaccines, as recommended by the World Health Organization. Influenza B virus vaccines for humans have been available for more than half a century, yet no systematic efforts have been undertaken to develop high-yield candidates. Therefore, we screened virus libraries possessing random mutations in the six "internal" influenza B viral RNA segments [i.e., those not encoding the major viral antigens, hemagglutinin (HA) and neuraminidase NA)] for mutants that confer efficient replication. Candidate viruses that supported high yield in cell culture were tested with the HA and NA genes of eight different viruses of the Victoria and Yamagata lineages. We identified combinations of mutations that increased the titers of candidate vaccine viruses in mammalian cells used for human influenza vaccine virus propagation and in embryonated chicken eggs, the most common propagation system for influenza viruses. These influenza B virus vaccine backbones can be used for improved vaccine virus production.

Serum ALT levels as a surrogate marker for serum HBV DNA levels in HBeAg-negative pregnant women.

PubMed

Sangfelt, Per; Von Sydow, Madeleine; Uhnoo, Ingrid; Weiland, Ola; Lindh, Gudrun; Fischler, Björn; Lindgren, Susanne; Reichard, Olle

2004-01-01

In Stockholm, Sweden, the majority of pregnant women positive for hepatitis B surface antigen (HBsAg) are hepatitis Be antigen (HBeAg) negative. Newborns to HBeAg positive mothers receive vaccination and hepatitis B immunoglobulin (HBIg). Newborns to HBeAg negative mothers receive vaccine and HBIg only if the mothers have elevated ALT levels. The aim of this study was to retrospectively evaluate ALT levels as a surrogate marker for HBV DNA levels in HBeAg negative carrier mothers. Altogether 8947 pregnant women were screened for HBV markers from 1999 to 2001 at the Virology Department, Karolinska Hospital. Among mothers screened 192 tested positive for HBsAg (2.2%). 13 of these samples could not be retrieved. Of the remaining 179 sera, 8 (4%) tested positive for HBeAg and 171 (95.5%) were HBeAg negative. Among the HBeAg negative mothers, 9 had HBV DNA levels > 10(5) copies/ml, and of these 7 had normal ALT levels indicating low sensitivity of an elevated ALT level as a surrogate marker for high HBV DNA level. Furthermore, no correlation was found between ALT and HBV DNA levels. Hence, it is concluded that the use of ALT as a surrogate marker for high viral replication in HBeAg negative mothers could be questioned.

Lay Health Worker Intervention Improved Compliance with Hepatitis B Vaccination in Asian Americans: Randomized Controlled Trial.

PubMed

Juon, Hee-Soon; Strong, Carol; Kim, Frederic; Park, Eunmi; Lee, Sunmin

2016-01-01

This study aimed to evaluate the effect of a lay health worker (LHW) telephone intervention on completing a series of hepatitis B virus (HBV) vaccinations among foreign-born Asian Americans in the Baltimore-Washington Metropolitan area. During the period of April 2013 and March 2014, we recruited Asian Americans who were 18 years of age and older in the community-based organizations. Of the 645 eligible participants, 600 (201 Chinese, 198 Korean, 201 Vietnamese) completed a pretest survey and received hepatitis B screening. Based on the screening results, we conducted a randomized controlled trial among those unprotected (HBsAg-/HBsAB-) by assigning them either to an intervention group (n = 124) or control group (n = 108). The intervention group received a list of resources by mails for where to get free vaccinations as well as reminder calls for vaccinations from trained LHWs, while the control group received only list of resources by mail. Seven months after mailing the HBV screening results, trained LHWs followed up with all participants by phone to ask how many of the recommended series of 3 vaccinations they had received: none, 1 or 2, or all 3 (complete). Their self-reported vaccinations were verified with the medical records. Multinomial logistic regressions were used to examine the effect of the LHW intervention. Process evaluation was conducted by asking study participants in the intervention group to evaluate the performance of the LHWs. After seven months, those in the intervention group were more likely to have 1 or more vaccines than the control group, compared to the no vaccination group (OR = 3.04, 95% CI, 1.16, 8.00). Also, those in the intervention group were more likely to complete a series of vaccinations than the control group, compared to the no vaccination group (OR = 7.29, 95% CI 3.39, 15.67). The most important barrier preventing them from seeking hepatitis B vaccinations was lack of time to get the vaccination. The most important promoters

Vaccines against meningococcal serogroup B disease containing outer membrane vesicles (OMV)

PubMed Central

Holst, Johan; Oster, Philipp; Arnold, Richard; Tatley, Michael V.; Næss, Lisbeth M.; Aaberge, Ingeborg S.; Galloway, Yvonne; McNicholas, Anne; O’Hallahan, Jane; Rosenqvist, Einar; Black, Steven

2013-01-01

The utility of wild-type outer membrane vesicle (wtOMV) vaccines against serogroup B (MenB) meningococcal disease has been explored since the 1970s. Public health interventions in Cuba, Norway and New Zealand have demonstrated that these protein-based vaccines can prevent MenB disease. Data from large clinical studies and retrospective statistical analyses in New Zealand give effectiveness estimates of at least 70%. A consistent pattern of moderately reactogenic and safe vaccines has been seen with the use of approximately 60 million doses of three different wtOMV vaccine formulations. The key limitation of conventional wtOMV vaccines is their lack of broad protective activity against the large diversity of MenB strains circulating globally. The public health intervention in New Zealand (between 2004–2008) when MeNZB was used to control a clonal MenB epidemic, provided a number of new insights regarding international and public-private collaboration, vaccine safety surveillance, vaccine effectiveness estimates and communication to the public. The experience with wtOMV vaccines also provide important information for the next generation of MenB vaccines designed to give more comprehensive protection against multiple strains. PMID:23857274

Characteristics of a new meningococcal serogroup B vaccine, bivalent rLP2086 (MenB-FHbp; Trumenba®).

PubMed

Gandhi, Ashesh; Balmer, Paul; York, Laura J

2016-08-01

Neisseria meningitidis is a common cause of bacterial meningitis, often leading to permanent sequelae or death. N. meningitidis is classified into serogroups based on the composition of the bacterial capsular polysaccharide; the 6 major disease-causing serogroups are designated A, B, C, W, X, and Y. Four of the 6 disease-causing serogroups (A, C, Y, and W) can be effectively prevented with available quadrivalent capsular polysaccharide protein conjugate vaccines; however, capsular polysaccharide conjugate vaccines are not effective against meningococcal serogroup B (MnB). There is no vaccine available for serogroup X. The public health need for an effective serogroup B vaccine is evident, as MnB is the most common cause of meningococcal disease in the United States and is responsible for almost half of all cases in persons aged 17 to 22 years. In fact, serogroup B meningococci were responsible for the recent meningococcal disease outbreaks on college campuses. However, development of a suitable serogroup B vaccine has been challenging, as serogroup B polysaccharide-based vaccines were found to be poorly immunogenic. Vaccine development for MnB focused on identifying potential outer membrane protein targets that elicit broadly protective immune responses across strains from the vast number of proteins that exist on the bacterial surface. Human factor H binding protein (fHBP; also known as LP2086), a conserved surface-exposed bacterial lipoprotein, was identified as a promising vaccine candidate. Two recombinant protein-based serogroup B vaccines that contain fHBP have been successfully developed and licensed in the United States under an accelerated approval process: bivalent rLP2086 (MenB-FHbp; Trumenba®) and 4CMenB (MenB-4 C; Bexsero®). This review will focus on bivalent rLP2086 only, including vaccine components, mechanism of action, and potential coverage across serogroup B strains in the United States.

Designer vaccine nanodiscs for personalized cancer immunotherapy

NASA Astrophysics Data System (ADS)

Kuai, Rui; Ochyl, Lukasz J.; Bahjat, Keith S.; Schwendeman, Anna; Moon, James J.

2017-04-01

Despite the tremendous potential of peptide-based cancer vaccines, their efficacy has been limited in humans. Recent innovations in tumour exome sequencing have signalled the new era of personalized immunotherapy with patient-specific neoantigens, but a general methodology for stimulating strong CD8α+ cytotoxic T-lymphocyte (CTL) responses remains lacking. Here we demonstrate that high-density lipoprotein-mimicking nanodiscs coupled with antigen (Ag) peptides and adjuvants can markedly improve Ag/adjuvant co-delivery to lymphoid organs and sustain Ag presentation on dendritic cells. Strikingly, nanodiscs elicited up to 47-fold greater frequencies of neoantigen-specific CTLs than soluble vaccines and even 31-fold greater than perhaps the strongest adjuvant in clinical trials (that is, CpG in Montanide). Moreover, multi-epitope vaccination generated broad-spectrum T-cell responses that potently inhibited tumour growth. Nanodiscs eliminated established MC-38 and B16F10 tumours when combined with anti-PD-1 and anti-CTLA-4 therapy. These findings represent a new powerful approach for cancer immunotherapy and suggest a general strategy for personalized nanomedicine.

Hepatitis B vaccination for injection drug users--Pierce County, Washington, 2000.

PubMed

2001-05-18

Hepatitis B vaccination has been recommended for injection drug users (IDUs) since 1982, but vaccination coverage of IDUs remains low (1), and outbreaks of hepatitis B among IDUs continue to occur. An outbreak of hepatitis B primarily among IDUs in Pierce County, Washington, detected in April 2000, included 60 cases and resulted in three deaths among IDUs co-infected with hepatitis delta virus. A program to administer hepatitis B vaccine to IDUs was implemented to control the outbreak, and the number of cases identified decreased from 13 per month in May to two cases since November. This report describes a vaccination program during which IDUs accepted hepatitis B vaccination provided free of charge in community-based settings and illustrates how effective hepatitis B vaccination programs targeted at IDUs can be implemented through collaborations between departments of health and corrections and community organizations.

Safety of currently licensed hepatitis B surface antigen vaccines in the United States, Vaccine Adverse Event Reporting System (VAERS), 2005-2015.

PubMed

Haber, Penina; Moro, Pedro L; Ng, Carmen; Lewis, Paige W; Hibbs, Beth; Schillie, Sarah F; Nelson, Noele P; Li, Rongxia; Stewart, Brock; Cano, Maria V

2018-01-25

Currently four recombinant hepatitis B (HepB) vaccines are in use in the United States. HepB vaccines are recommended for infants, children and adults. We assessed adverse events (AEs) following HepB vaccines reported to the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system. We searched VAERS for reports of AEs following single antigen HepB vaccine and HepB-containing vaccines (either given alone or with other vaccines), from January 2005 - December 2015. We conducted descriptive analyses and performed empirical Bayesian data mining to assess disproportionate reporting. We reviewed serious reports including reports of special interest. VAERS received 20,231 reports following HepB or HepB-containing vaccines: 10,291 (51%) in persons <2 years of age; 2588 (13%) in persons 2-18 years and 5867 (29%) in persons >18 years; for 1485 (7.3%) age was missing. Dizziness and nausea (8.4% each) were the most frequently reported AEs following a single antigen HepB vaccine: fever (23%) and injection site erythema (11%) were most frequent following Hep-containing vaccines. Of the 4444 (22%) reports after single antigen HepB vaccine, 303 (6.8%) were serious, including 45 deaths. Most commonly reported cause of death was Sudden Infant Death Syndrome (197). Most common non-death serious reports following single antigen HepB vaccines among infants aged <1 month, were nervous system disorders (15) among children aged 1-23 months; infections and infestation (8) among persons age 2-18 years blood and lymphatic systemic disorders; and general disorders and administration site conditions among persons age >18 years. Most common vaccination error following single antigen HepB was incorrect product storage. Review current U.S.-licensed HepB vaccines administered alone or in combination with other vaccines did not reveal new or unexpected safety concerns. Vaccination errors were identified which indicate the need for training and education

Serological markers of Hepatitis B and C among juvenile immigrants from Albania settled in Greece.

PubMed

Milionis, Charalampos

2010-12-01

Greece is a place of settlement for a large number of immigrants, particularly from Albania, which constitute special community groups for public health policies. This study was designed to assess the seroprevalence of serological markers for Hepatitis B and C among juvenile immigrants from Albania settled in Greece. The study population included 504 subjects, 418 males and 86 females, aged 10-23 years old who have emigrated from Albania to Pogoniani-Greece and participated voluntarily in vaccination programmes against Hepatitis B. The serum samples were examined with enzyme immune assays for the immunological markers HBsAg, anti-HBc, anti-HBs and anti-HCV. HBsAg positive samples were further tested for IgM anti-HBc, HBeAg and anti-HBe. Among the examined subjects, 40.5% were found positive for anti-HBc, indicating an HBV contamination. Specifically, 11.7% were carriers of HBsAg, whereas 28.8% were negative for HBsAg but positive for anti-HBc. Only 6.5% was positive exclusively for anti-HBs. The rest (53.0%) presented no positive serological markers. Among the HBsAg positive patients, 8.5% were found positive for HBeAg, while 5.1% was positive for IgM anti-HBc. Finally, only 0.6% of the sample presented antibodies against HCV. The examined migratory population is described by a high prevalence of Hepatitis B. Therefore, specific public health measures are necessary. However, no data was found that indicate potential public health dangers regarding hepatitis C.

Synthetic Long Peptide Influenza Vaccine Containing Conserved T and B Cell Epitopes Reduces Viral Load in Lungs of Mice and Ferrets

PubMed Central

Rosendahl Huber, S. K.; Camps, M. G. M.; Jacobi, R. H. J.; Mouthaan, J.; van Dijken, H.; van Beek, J.; Ossendorp, F.; de Jonge, J.

2015-01-01

Currently licensed influenza vaccines mainly induce antibodies against highly variable epitopes. Due to antigenic drift, protection is subtype or strain-specific and regular vaccine updates are required. In case of antigenic shifts, which have caused several pandemics in the past, completely new vaccines need to be developed. We set out to develop a vaccine that provides protection against a broad range of influenza viruses. Therefore, highly conserved parts of the influenza A virus (IAV) were selected of which we constructed antibody and T cell inducing peptide-based vaccines. The B epitope vaccine consists of the highly conserved HA2 fusion peptide and M2e peptide coupled to a CD4 helper epitope. The T epitope vaccine comprises 25 overlapping synthetic long peptides of 26-34 amino acids, thereby avoiding restriction for a certain MHC haplotype. These peptides are derived from nucleoprotein (NP), polymerase basic protein 1 (PB1) and matrix protein 1 (M1). C57BL/6 mice, BALB/c mice, and ferrets were vaccinated with the B epitopes, 25 SLP or a combination of both. Vaccine-specific antibodies were detected in sera of mice and ferrets and vaccine-specific cellular responses were measured in mice. Following challenge, both mice and ferrets showed a reduction of virus titers in the lungs in response to vaccination. Summarizing, a peptide-based vaccine directed against conserved parts of influenza virus containing B and T cell epitopes shows promising results for further development. Such a vaccine may reduce disease burden and virus transmission during pandemic outbreaks. PMID:26046664

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.

Hepatitis B vaccine immunogenicity among adults vaccinated during an outbreak response in an assisted living facility—Virginia, 2010

PubMed Central

Bender, Thomas John; Sharapov, Umid; Utah, Okey; Xing, Jian; Hu, Dale; Rybczynska, Jolanta; Drobeniuc, Jan; Kamili, Saleem; Spradling, Philip R.; Moorman, Anne C.

2017-01-01

Background Failure to adhere to infection control guidelines, especially during assisted monitoring of blood glucose, has caused multiple hepatitis B outbreaks in assisted living facilities (ALFs). In conjunction with the response to such an outbreak at an ALF (“Facility X”) where most residents had neuropsychiatric disorders, we evaluated seroprotection rates conferred by hepatitis B vaccine and assessed the influence of demographic factors on vaccine response. Methods Residents were screened for hepatitis B and C infection, and those susceptible were vaccinated against hepatitis A and hepatitis B with one dose of TWINRIX™ (GSK) given at 0, 1, and 7 months. Blood samples were collected 1–2 months after receipt of the third vaccine dose to test for antibody to hepatitis B surface antigen (anti-HBs). Results Of the 27 residents who had post-vaccination blood specimens collected, 22 (81%) achieved anti-HBs concentrations ≥10 mIU/mL. Neither age nor neuropsychiatric comorbidity was a significant determinant of seroprotection. Geometric mean concentration was lower among residents aged 60–74 years (74.3 mIU/mL) than among residents aged 46–59 years (105.3 mIU/mL) but highest among residents aged ≥75 years (122.5 mIU/mL). The effect of diabetes on vaccination response could not be examined because 16/17 (94%) diabetic residents had HBV infection by the time of investigation. Conclusions Adult vaccine recipients of all ages, even those over 60 years of age, demonstrated a robust capacity for achieving hepatitis B seroprotection in response to the combined hepatitis A/hepatitis B vaccine. The role for vaccination in interrupting HBV transmission during an outbreak remains unclear, but concerns about age-related response to hepatitis B vaccine may be insufficient to justify foregoing vaccination of susceptible residents of ALFs. PMID:24370706

Differentiation of Mycoplasma gallisepticum vaccine strains ts-11 and 6/85 from commonly used Mycoplasma gallisepticum challenge strains by PCR.

PubMed

Evans, J D; Leigh, S A

2008-09-01

Mycoplasma gallisepticum (MG) is an important avian pathogen causing significant economic losses within the poultry industry. In an effort to develop tools to aid in MG research and diagnostics, we have compared sequences of the attenuated MG vaccine strain ts-11 to those of commonly used pathogenic challenge strains in search of a simple means of differentiation. Via gapA sequence alignments and comparisons, we have identified and designed primers facilitating strain differentiation. When applied to conventional polymerase chain reaction (PCR) assay at low annealing temperature, the primer sets allow for the differentiation of MG attenuated vaccine strains ts-11 as well as the attenuated MG vaccine strain 6/85 from the commonly utilized MG challenge strains R(low), R, and S6. Conventional PCR differentiation is based on the visualization of sole products with the attenuated MG strains ts-11 and 6/85 and the lack of the corresponding products from MG strains R(low), R, and S6. When applied to MG strain F, product visualization varies with the applied primer set. The differentiation of MG strains ts-11 and 6/85 from the pathogenic challenge strains was also accomplished via real-time analyses, however, the primer sets were not able to differentiate MG strains ts-11 and 6/85 from selected MG field isolates.

Compliance with a Voluntary Hepatitis B Vaccination Program.

ERIC Educational Resources Information Center

Rowe, Todd K.; Douglass, Chester W.

1988-01-01

Three years after the introduction of a voluntary hepatitis B vaccination program, the Harvard School of Dental Medicine has achieved a high vaccination rate among predoctoral students and a moderate rate among postdoctoral students and faculty. However, an unexpectedly low immunity was achieved, even among vaccinated individuals. (MSE)

Increasing Coverage of Hepatitis B Vaccination in China

PubMed Central

Wang, Shengnan; Smith, Helen; Peng, Zhuoxin; Xu, Biao; Wang, Weibing

2016-01-01

Abstract This study used a system evaluation method to summarize China's experience on improving the coverage of hepatitis B vaccine, especially the strategies employed to improve the uptake of timely birth dosage. Identifying successful methods and strategies will provide strong evidence for policy makers and health workers in other countries with high hepatitis B prevalence. We conducted a literature review included English or Chinese literature carried out in mainland China, using PubMed, the Cochrane databases, Web of Knowledge, China National Knowledge Infrastructure, Wanfang data, and other relevant databases. Nineteen articles about the effectiveness and impact of interventions on improving the coverage of hepatitis B vaccine were included. Strong or moderate evidence showed that reinforcing health education, training and supervision, providing subsidies for facility birth, strengthening the coordination among health care providers, and using out-of-cold-chain storage for vaccines were all important to improving vaccination coverage. We found evidence that community education was the most commonly used intervention, and out-reach programs such as out-of-cold chain strategy were more effective in increasing the coverage of vaccination in remote areas where the facility birth rate was respectively low. The essential impact factors were found to be strong government commitment and the cooperation of the different government departments. Public interventions relying on basic health care systems combined with outreach care services were critical elements in improving the hepatitis B vaccination rate in China. This success could not have occurred without exceptional national commitment. PMID:27175710

Live Attenuated Salmonella Vaccines Displaying Regulated Delayed Lysis and Delayed Antigen Synthesis To Confer Protection against Mycobacterium tuberculosis

PubMed Central

Juárez-Rodríguez, María Dolores; Yang, Jiseon; Kader, Rebin; Alamuri, Praveen; Curtiss, Roy

2012-01-01

Live recombinant attenuated Salmonella vaccine (RASV) strains have great potential to induce protective immunity against Mycobacterium tuberculosis by delivering M. tuberculosis antigens. Recently, we reported that, in orally immunized mice, RASV strains delivering the M. tuberculosis early secreted antigenic target 6-kDa (ESAT-6) protein and culture filtrate protein 10 (CFP-10) antigens via the Salmonella type III secretion system (SopE amino-terminal region residues 1 to 80 with two copies of ESAT-6 and one copy of CFP-10 [SopENt80-E2C]) afforded protection against aerosol challenge with M. tuberculosis. Here, we constructed and evaluated an improved Salmonella vaccine against M. tuberculosis. We constructed translational fusions for the synthesis of two copies of ESAT-6 plus CFP-10 fused to the OmpC signal sequence (OmpCSS-E2C) and amino acids 44 to 338 of antigen 85A (Ag85A294) flanked by the signal sequence (SS) and C-terminal peptide (CT) of β-lactamase (BlaSS-Ag85A294-BlaCT) to enable delivery via the Salmonella type II secretion system. The genes expressing these proteins were cloned as an operon transcribed from Ptrc into isogenic Asd+/MurA+ pYA3681 lysis vector derivatives with different replication origins (pBR, p15A, pSC101), resulting in pYA4890, pYA4891, and pYA4892 for SopENt80-E2C/Ag85A294 synthesis and pYA4893 and pYA4894 for OmpCSS-E2C/Ag85A294 synthesis. Mice orally immunized with the RASV χ11021 strain engineered to display regulated delayed lysis and regulated delayed antigen synthesis in vivo and harboring pYA4891, pYA4893, or pYA4894 elicited significantly greater humoral and cellular immune responses, and the RASV χ11021 strain afforded a greater degree of protection against M. tuberculosis aerosol challenge in mice than RASVs harboring any other Asd+/MurA+ lysis plasmid and immunization with M. bovis BCG, demonstrating that RASV strains displaying regulated delayed lysis with delayed antigen synthesis resulted in highly immunogenic

The effects of different dosage levels of hepatitis B vaccine as booster on anti-HBs-negative children 5–15 y after primary immunization; China, 2009–2010

PubMed Central

Chen, Yongdi; Lv, Huakun; Gu, Hua; Cui, Fujiang; Wang, Fuzhen; Yao, Jun; Xia, Shichang; Liang, Xiaofeng

2014-01-01

The changes in lgG antibody levels to hepatitis B surface antigen (HBsAg) and in antibody to HBsAg (anti-HBs) seroconversion rates due to different dosages of hepatitis B vaccine (HepB) were compared in 2106 children. Children who had been previously vaccinated as infants with HepB were revaccinated at 5–15 y of age, after which the antibody titers were determined. After the first booster dose, the anti-HBs seroconversion rate (defined as an anti-HBs ≥10 mIU/ml) with 10 μg of HepB (93.6%) was significantly greater than the rate with 5 µg of HepB (90.3%) (P < 0.05); the anti-HBs seroconversion rate in 10–15-y-old boys vaccinated with 10 μg of HepB (90.9%) was significantly greater than the rate with 5 µg of HepB (84.3%) (P < 0.05). The anti-HBs seroconversion rates after the third booster dose with 5 or 10 μg of HepB were greater than those after the first booster dose (99.6% and 99.7%, vs. 90.3% and 93.6%, P < 0.05); as was the corresponding GMTs (658 ± 4 mIU/ml and 2599 ± 3 mIU/ml, vs. 255 ± 11 mIU/ml and 877 ± 11 mIU/ml [P < 0.05]). The immunization effects of booster vaccination with 3 doses of HepB with 5 or 10 µg are effective; a single booster dose with 10 µg of HepB for 10–15-y-old boys and with 5 or 10 µg of HepB for 5–9 y old boys and for 5–15-y-old girls are effective in generating protective antibody against HBV; however, for anti-HBs-negative children after a single dose of booster, 3 doses are needed. PMID:24192508

Hepatitis B vaccination of male neonates and autism diagnosis, NHIS 1997-2002.

PubMed

Gallagher, Carolyn M; Goodman, Melody S

2010-01-01

Universal hepatitis B vaccination was recommended for U.S. newborns in 1991; however, safety findings are mixed. The association between hepatitis B vaccination of male neonates and parental report of autism diagnosis was determined. This cross-sectional study used weighted probability samples obtained from National Health Interview Survey 1997-2002 data sets. Vaccination status was determined from the vaccination record. Logistic regression was used to estimate the odds for autism diagnosis associated with neonatal hepatitis B vaccination among boys age 3-17 years, born before 1999, adjusted for race, maternal education, and two-parent household. Boys vaccinated as neonates had threefold greater odds for autism diagnosis compared to boys never vaccinated or vaccinated after the first month of life. Non-Hispanic white boys were 64% less likely to have autism diagnosis relative to nonwhite boys. Findings suggest that U.S. male neonates vaccinated with the hepatitis B vaccine prior to 1999 (from vaccination record) had a threefold higher risk for parental report of autism diagnosis compared to boys not vaccinated as neonates during that same time period. Nonwhite boys bore a greater risk.

Comparison of two vaccination strategies against hepatitis A and B in patients with chronic hepatitis C.

PubMed

Díez Redondo, M P; Almaraz, A; Jiménez Rodríguez-Vila, M; Santamaría, A; de Castro, J; Torrego, J C; Caro-Patón, A

2009-04-01

although the vaccination against hepatitis A (VAH) and hepatitis B (VBH) is recommended in patients with HCV, the most cost-effective strategy has not been established. Our objective was to compare the cost-effectiveness of universal strategy (vaccination all patients) with selective strategy (vaccination only patients against virus they lack immunity to) in patients with HCV. we compared the direct medical costs of the two vaccination strategies against both viruses in 313 patients with HC. Serological markers for HAV (anti-HAV) and HBV (HbsAg, anti HBs, anti HBc) were determined in the 313 patients and the costs of the vaccines and the blood tests necessary to determinate the immunity state in our care system were considered. the prevalence of anti-HAV was 81,2% and of anti-HBc was 24,6%. The prevalence of anti-HAV increases with age. HAV vaccination with universal strategy has a cost of 19.806,64 euro and with selective one of 9.899,62 euro. HBV vaccination with universal strategy rose to 18.780 euro and to 20.385,57 euro with selective one (employing anti-HBc). Costs were analysed in different groups of age and several hepatitis HBV risk factors. the selective vaccination strategy against HAV was most cost-effective in our patients with HCV. However, when the prevalence of the anti-HAV decreased to less than 20% universal strategy will be the best option. Difference of cost-effective between the two vaccination strategies against HBV was small, on behalf of universal one, so in groups with higher anti-HBc prevalence, like parenteral drugs users and tattoos, the selective strategy could be the best option.

Targeting the Intratumoral Dendritic Cells by the Oncolytic Adenoviral Vaccine Expressing RANTES Elicits Potent Antitumor Immunity

PubMed Central

Lapteva, Natalia; Aldrich, Melissa; Weksberg, David; Rollins, Lisa; Goltsova, Tatiana; Chen, Si-Yi; Huang, Xue F.

2014-01-01

Summary Dendritic cells (DCs) are professional antigen (Ag)-presenting cells capable of inducing immune responses to tumor Ags and, therefore, play a central role in the induction of antitumor immunity. There is a large amount of evidence, however, about paucity of tumor-associated DCs and that DCs’ immunogenic functions are suppressed in a tumor environment. Here we describe a potent in situ vaccine targeting tumoral DCs in vivo. This vaccine comprised of an oncolytic adenovirus expressing RANTES (regulated upon activation, normally T expressed, and presumably secreted) (Ad-RANTES-E1A), enhanced tumor infiltration, and maturation of Ag-presenting cells in vivo. In this study, we show that intratumoral vaccinations with Ad-RANTES-E1A induced significant primary tumor growth regression and blocked metastasis formation in JC and E.G-7 murine tumor models. This vaccine recruited DCs, macrophages, natural killer cells, and CD8+ T cells to the tumor site, and thus enhanced Ag-specific cytotoxic T lymphocyte responses and natural killer cell responses. DCs purified from the Ad-RANTES-E1A–treated E.G-7 tumors secreted significantly higher levels of interferon-γ and interleukin-12, as compared with control groups and more efficiently enhanced CD8+ T-cell response. This in situ immunization strategy could be a potent antitumor immunotherapy approach for aggressive established tumors. PMID:19238013

Heat killed Saccharomyces cerevisiae as an adjuvant for the induction of vaccine-mediated immunity against infection with Mycobacterium tuberculosis.

PubMed

Grover, Ajay; McLean, Jennifer L; Troudt, JoLynn M; Foster, Chad; Izzo, Linda; Creissen, Elisabeth; MacDonald, Elisabeth; Troy, Amber; Izzo, Angelo A

2016-05-27

The use of novel vaccine delivery systems allows for the manipulation of the adaptive immune systems through the use of molecular adjuvants that target specific innate pathways. Such strategies have been used extensively for vaccines against cancer and multiple pathogens such as Mycobacterium tuberculosis. In the current study we used heat killed non-pathogenic recombinant Saccharomyces cerevisiae expressing M. tuberculosis antigen Rv1886c (fbpB, mpt59, Ag85B) as a delivery system in conjunction with its ability to stimulate innate immunity to determine its ability to induce immunity. We established that the recombinant yeast induced activated antigen specific T cells are capable of reducing the mycobacterial burden. Inoculation of the recombinant yeast after vaccination with BCG resulted in a systemic alteration of the phenotype of the immune response although this was not reflected in an increase in the reduction of the mycobacterial burden. Taken together the data suggest that heat killed yeast can induce multiple cytokines required for induction of protective immunity and can function as a vehicle for delivery of M. tuberculosis antigens in a vaccine formulation. In addition, while it can enhance the effector memory response induced by BCG, it had little effect on central memory responses. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biotechnology and the transformation of vaccine innovation: The case of the hepatitis B vaccines 1968-2000.

PubMed

Huzair, Farah; Sturdy, Steve

2017-08-01

The approval, from 1986, of a series of recombinant hepatitis B vaccines was a landmark both in the growth of biotechnology and in the development of the vaccine innovation system. In this paper, we show how the early development of the hepatitis B vaccines was shaped by a political and economic context that newly favoured commercialisation of academic research, including the appropriation and management of intellectual property; we elucidate the contingent interests and motivations that led new biotechnology companies and established pharmaceutical businesses to invest in developing recombinant vaccines specifically against hepatitis B; and we show how these and other factors combined to make those vaccines an unexpected commercial success. Broadening the scope of our analysis to include not just North America and Europe but also low- and middle-income countries, we show how the development of the hepatitis B vaccines facilitated the emergence of a two-tier innovation system structured by tensions between the demands for commercial profitability on the one hand, and the expectation of public health benefit for low- and middle-income countries on the other. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Acute hepatitis B virus infection with simultaneous high HBsAg and high anti-HBs signals in a previously HBV vaccinated HIV-1 positive patient.

PubMed

van Dommelen, Laura; Verbon, Annelies; van Doorn, H Rogier; Goossens, Valère J

2010-03-01

We present a case of a clinical manifest hepatitis B virus infection and a potentially misleading HBV serological profile in an HIV-1 positive patient despite previous HBV vaccination. The patient presented with an acute hepatitis B and there was no indication of chronic HBV infection or the presence of a mutation in the 'a' determinant. Remarkably, simultaneously with high HBV surface antigen and HBV viral load, high anti-HBs antibodies were present. If, due to previous HBV vaccination only anti-HBs was tested in this patient, the result of the high anti-HBs antibodies could be very misleading and offering a false sense of security. Our findings contribute to the ongoing discussion on how to assess HBV specific immunological memory and determining the role of HBV booster vaccinations in immunocompromised individuals.

Frequency of hepatitis B surface antigen variants (HBsAg) in hepatitis B virus genotype B and C infected East- and Southeast Asian patients: Detection by the Elecsys® HBsAg II assay.

PubMed

Kim, Hyon Suk; Chen, Xinyue; Xu, Min; Yan, Cunling; Liu, Yali; Deng, Haohui; Hoang, Bui Huu; Thuy, Pham Thi Thu; Wang, Terry; Yan, Yiwen; Zeng, Zhen; Gencay, Mikael; Westergaard, Gaston; Pabinger, Stephan; Kriegner, Albert; Nauck, Markus; Seffner, Anja; Gohl, Peter; Hübner, Kirsten; Kaminski, Wolfgang E

2018-06-01

To avoid false negative results, hepatitis B surface antigen (HBsAg) assays need to detect samples with mutations in the immunodominant 'a' determinant region, which vary by ethnographic region. We evaluated the prevalence and type of HBsAg mutations in a hepatitis B virus (HBV)-infected East- and Southeast Asian population, and the diagnostic performance of the Elecsys ® HBsAg II Qualitative assay. We analyzed 898 samples from patients with HBV infection from four sites (China [Beijing and Guangzhou], Korea and Vietnam). HBsAg mutations were detected and sequenced using highly sensitive ultra-deep sequencing and compared between the first (amino acids 124-137) and second (amino acids 139-147) loops of the 'a' determinant region using the Elecsys ® HBsAg II Qualitative assay. Overall, 237 distinct amino acid mutations in the major hydrophilic region were identified; mutations were present in 660 of 898 HBV-infected patient samples (73.5%). Within the pool of 237 distinct mutations, the majority of the amino acid mutations were found in HBV genotype C (64.8%). We identified 25 previously unknown distinct mutations, mostly prevalent in genotype C-infected Korean patients (n = 18) followed by Chinese (n = 12) patients. All 898 samples were correctly identified by the Elecsys ® HBsAg II Qualitative assay. We observed 237 distinct (including 25 novel) mutations, demonstrating the complexity of HBsAg variants in HBV-infected East- and Southeast Asian patients. The Elecsys ® HBsAg II Qualitative assay can reliably detect HBV-positive samples and is suitable for routine diagnostic use in East and Southeast Asia. Copyright © 2018 Roche Diagnostics International Ltd. Published by Elsevier B.V. All rights reserved.

Prediction of conformational changes by single mutation in the hepatitis B virus surface antigen (HBsAg) identified in HBsAg-negative blood donors.

PubMed

Ie, Susan I; Thedja, Meta D; Roni, Martono; Muljono, David H

2010-11-18

Selection of hepatitis B virus (HBV) by host immunity has been suggested to give rise to variants with amino acid substitutions at or around the 'a' determinant of the surface antigen (HBsAg), the main target of antibody neutralization and diagnostic assays. However, there have never been successful attempts to provide evidence for this hypothesis, partly because the 3 D structure of HBsAg molecules has not been determined. Tertiary structure prediction of HBsAg solely from its primary amino acid sequence may reveal the molecular energetic of the mutated proteins. We carried out this preliminary study to analyze the predicted HBsAg conformation changes of HBV variants isolated from Indonesian blood donors undetectable by HBsAg assays and its significance, compared to other previously-reported variants that were associated with diagnostic failure. Three HBV variants (T123A, M133L and T143M) and a wild type sequence were analyzed together with frequently emerged variants T123N, M133I, M133T, M133V, and T143L. Based on the Jameson-Wolf algorithm for calculating antigenic index, the first two amino acid substitutions resulted in slight changes in the antigenicity of the 'a' determinant, while all four of the comparative variants showed relatively more significant changes. In the pattern T143M, changes in antigenic index were more significant, both in its coverage and magnitude, even when compared to variant T143L. These data were also partially supported by the tertiary structure prediction, in which the pattern T143M showed larger shift in the HBsAg second loop structure compared to the others. Single amino acid substitutions within or near the 'a' determinant of HBsAg may alter antigenicity properties of variant HBsAg, which can be shown by both its antigenic index and predicted 3 D conformation. Findings in this study emphasize the significance of variant T143M, the prevalent isolate with highest degree of antigenicity changes found in Indonesian blood donors. This

Hepatitis B vaccination among primary health care workers in Northwest Pakistan

PubMed Central

Yousafzai, Mohammad Tahir; Qasim, Rubina; Khalil, Rehana; Kakakhel, Mohammad Fazil; Rehman, Shafiq Ur

2014-01-01

Background We assessed hepatitis B vaccination and its determinants among health care workers (HCW) in rural Northwest Pakistan. Methods This cross sectional study was conducted among 485 HCWs from both public and private clinics. Data about hepatitis B vaccination, socio-demographic, knowledge regarding modes of transmission of hepatitis B virus, perceived disease severity and benefits of vaccination was collected through questionnaire. Multivariable logistic regression analysis was performed. Results Prevalence of complete hepatitis B vaccination was 40% (among Physicians with MBBS/MD qualification; 86% and lowest among non-qualified Dispensers;16%). Also, prevalence was higher among HCWs from public Dispensaries (77%) than those working in private clinics (35%). Being MBBS/MD Physician (Adj. OR 26.60; 95%CI 9.27–73.23), Non-MBBS/MD Physician (Adj.OR 1.89; 95%CI 0.78–4.59), qualified Dispensers (Adj. OR 3.58; 95%CI 1.34–9.54) compared to non-qualified Dispensers, working in public clinics (Adj. OR 2.54; 95%CI 1.13–5.69) as compared to private, perceived disease threat after exposure to blood and body fluids (Adj. OR 1.11; 95%CI 1.03–1.19) and perceived benefits of hepatitis B vaccination (Adj. OR 1.13; 95%CI 1.09–1.19) were significant predictors of complete hepatitis B vaccination. Conclusion Improved perception of disease threat and benefits of vaccination and qualification of HCWs are associated with hepatitis B vaccination among Primary HCWs. PMID:24899881

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

Meningococcal serogroup B vaccine: Knowledge and acceptability among parents in Italy.

PubMed

Morrone, Teresa; Napolitano, Francesco; Albano, Luciana; Di Giuseppe, Gabriella

2017-08-03

This study aimed to evaluate the knowledge and attitudes about Meningococcal meningitis B and the relative vaccine for children among a sample of parents in Italy. A cross-sectional investigation was conducted from October to December 2015 among a sample of 910 parents in the geographic area of Naples and Salerno (Italy). In total, 543 of 910 parents returned a completed questionnaire for a response rate of 59.7%. Almost all parents had heard about meningitis (95.8%), 79.8% of these knew the mode of transmission (through respiratory droplets) and 62.5% knew the susceptible population (infants, children and adolescents). Moreover, a large percentage (86%) knew that the vaccine is a preventive measure. Parents who were married, those who had one child, those who did not have information about the MenB vaccine by physicians and those who needed additional information about the MenB vaccine were more likely to know the vaccine as a preventive measure of meningitis. Regarding attitudes toward the MenB vaccine, approximately two thirds of parents considered the vaccine useful (67.2%) and said that they would vaccinate their children (64.1%). Parents who had administered at least one recommended vaccination to their children, those who considered the vaccine useful, those with need for additional information about the vaccine and those who knew that the vaccine was a preventive measure of meningitis were more likely to have a positive attitude to vaccinating their children. Considering the results of our study, it looks appropriate that the knowledge of the population about meningitis and its related vaccinations is improved through correct health education and effective vaccine strategies that are implemented by policy makers.

Dose-dependent immunogenicity of a soluble Neospora caninum tachyzoite-extract vaccine formulated with a soy lecithin/β-glucan adjuvant in cattle.

PubMed

Mansilla, F C; Czepluch, W; Malacari, D A; Hecker, Y P; Bucafusco, D; Franco-Mahecha, O L; Moore, D P; Capozzo, A V

2013-10-18

Mice immunized with a soluble extract of Neospora caninum tachyzoites (sNcAg) formulated with Providean-AVEC, an aqueous soy-based adjuvant, are fully protected from N. caninum multiplication. Here we evaluated the dose-dependent immunogenicity of this vaccine formulation in cattle. Cattle (N=3 per group) were immunized with two applications (30 days apart) of formulations containing Providean-AVEC and different payloads of sNcAg (100, 50 and 10 μg), that were five to fifty times lower than the only reported study using this same antigen in cattle. Kinetics and magnitude of the vaccine-induced immune responses were dose-dependent. Cattle immunized with 100 μg-sNcAg elicited high-avidity specific antibodies 3 weeks after the primary vaccination while those that received 50 μg of antigen had maximum levels of specific high-avidity antibodies 5 days after the day 30 boost. Vaccination with 10 μg of sNcAg induced comparable antibody responses after 2 weeks post re-vaccination. IgG1 was the predominant isotype in all vaccinated animals. Maximum systemic IFN-γ levels were measured in cattle immunized with 50 and 100 μg-sNcAg (14 ± 2.8 ng/ml). CD4(+)-T cells from vaccinated animals proliferated after sNcAg stimulation in vitro, producing IFN-γ. Recall IFN-γ responses mediated by CD4(+)-T cells were detected up to 140 days post vaccination. Formulations containing Providean-AVEC and 50 μg of sNcAg stimulated broad cellular and humoral immune responses against N. caninum in cattle. The profile and magnitude of the immune response elicited by this vaccine can be modified by the antigen-dose and vaccination schedule. This is the first dose-response study performed in cattle using sNcAg as antigen. Copyright © 2013 Elsevier B.V. All rights reserved.

Application of a Newly Developed High-Sensitivity HBsAg Chemiluminescent Enzyme Immunoassay for Hepatitis B Patients with HBsAg Seroclearance

PubMed Central

Shinkai, Noboru; Matsuura, Kentaro; Sugauchi, Fuminaka; Watanabe, Tsunamasa; Murakami, Shuko; Iio, Etsuko; Ogawa, Shintaro; Nojiri, Shunsuke; Joh, Takashi

2013-01-01

We modified and automated a highly sensitive chemiluminescent enzyme immunoassay (CLEIA) for surface antigen (HBsAg) detection using a combination of monoclonal antibodies, each for a specific epitope of HBsAg, and by improving an earlier conjugation technique. Of 471 hepatitis B virus (HBV) carriers seen in our hospital between 2009 and 2012, 26 were HBsAg seronegative as determined by the Abbott Architect assay. The Lumipulse HBsAg-HQ assay was used to recheck those 26 patients who demonstrated seroclearance by the Abbott Architect assay. The performance of the Lumipulse HBsAg-HQ assay was compared with that of a quantitative HBsAg detection system (Abbott Architect) and the Roche Cobas TaqMan HBV DNA assay (CTM) (lower limit of detection, 2.1 log copies/ml) using blood serum samples from patients who were determined to be HBsAg seronegative by the Abbott Architect assay. Ten patients had spontaneous HBsAg loss. Of 8 patients treated with nucleotide analogues (NAs), two were HBsAg seronegative after stopping lamivudine therapy and 6 were HBsAg seronegative during entecavir therapy. Eight acute hepatitis B (AH) patients became HBsAg seronegative. Of the 26 patients, 16 were HBsAg positive by the Lumipulse HBsAg-HQ assay but negative by the Abbott Architect assay. The differences between the two assays in terms of detectable HBsAg persisted over the long term in the spontaneous loss group (median, 10 months), the NA-treated group (2.5 months), and the AH group (0.5 months). In 9 patients, the Lumipulse HBsAg-HQ assay detected HBsAg when HBV DNA was negative by the CTM assay. HBsAg was also detected by the Lumipulse HBsAg-HQ assay in 4 patients with an anti-HBs concentration of >10 mIU/ml, 3 of whom had no HBsAg escape mutations. The automatic, highly sensitive HBsAg CLEIA Lumipulse HBsAg-HQ is a convenient and precise assay for HBV monitoring. PMID:23946517

Application of a newly developed high-sensitivity HBsAg chemiluminescent enzyme immunoassay for hepatitis B patients with HBsAg seroclearance.

PubMed

Shinkai, Noboru; Matsuura, Kentaro; Sugauchi, Fuminaka; Watanabe, Tsunamasa; Murakami, Shuko; Iio, Etsuko; Ogawa, Shintaro; Nojiri, Shunsuke; Joh, Takashi; Tanaka, Yasuhito

2013-11-01

We modified and automated a highly sensitive chemiluminescent enzyme immunoassay (CLEIA) for surface antigen (HBsAg) detection using a combination of monoclonal antibodies, each for a specific epitope of HBsAg, and by improving an earlier conjugation technique. Of 471 hepatitis B virus (HBV) carriers seen in our hospital between 2009 and 2012, 26 were HBsAg seronegative as determined by the Abbott Architect assay. The Lumipulse HBsAg-HQ assay was used to recheck those 26 patients who demonstrated seroclearance by the Abbott Architect assay. The performance of the Lumipulse HBsAg-HQ assay was compared with that of a quantitative HBsAg detection system (Abbott Architect) and the Roche Cobas TaqMan HBV DNA assay (CTM) (lower limit of detection, 2.1 log copies/ml) using blood serum samples from patients who were determined to be HBsAg seronegative by the Abbott Architect assay. Ten patients had spontaneous HBsAg loss. Of 8 patients treated with nucleotide analogues (NAs), two were HBsAg seronegative after stopping lamivudine therapy and 6 were HBsAg seronegative during entecavir therapy. Eight acute hepatitis B (AH) patients became HBsAg seronegative. Of the 26 patients, 16 were HBsAg positive by the Lumipulse HBsAg-HQ assay but negative by the Abbott Architect assay. The differences between the two assays in terms of detectable HBsAg persisted over the long term in the spontaneous loss group (median, 10 months), the NA-treated group (2.5 months), and the AH group (0.5 months). In 9 patients, the Lumipulse HBsAg-HQ assay detected HBsAg when HBV DNA was negative by the CTM assay. HBsAg was also detected by the Lumipulse HBsAg-HQ assay in 4 patients with an anti-HBs concentration of >10 mIU/ml, 3 of whom had no HBsAg escape mutations. The automatic, highly sensitive HBsAg CLEIA Lumipulse HBsAg-HQ is a convenient and precise assay for HBV monitoring.

Antibody persistence and immune memory 4 years post-vaccination with combined hepatitis A and B vaccine in adults aged over 40 years.

PubMed

Chlibek, Roman; von Sonnenburg, Frank; Van Damme, Pierre; Smetana, Jan; Tichy, Petr; Gunapalaiah, Bhavyashree; Leyssen, Maarten; Jacquet, Jeanne-Marie

2011-01-01

Persistence of immune response was assessed in adults aged >40 years (N = 596) following primary vaccination with combined hepatitis A/B vaccine or concomitant monovalent hepatitis A and B vaccines. Anti-hepatitis A virus antibody responses persisted for at least 4 years regardless of the vaccine used, with anti-hepatitis B surface antibody responses higher and more sustained in subjects who received the combined hepatitis A/B vaccine. Response rates to an additional dose of the same vaccine(s) used for priming were high. © 2011 International Society of Travel Medicine.

64 FR 9042 - New Vaccine Information Materials for Hepatitis B, Haemophilus influenzae type b (Hib), and...

Federal Register 2010, 2011, 2012, 2013, 2014

1999-02-23

... children under 5 years old in the United States. Meningitis is an infection of the brain and spinal cord... Information Materials for Hepatitis B, Haemophilus influenzae type b (Hib), and Varicella (Chickenpox... vaccine information materials for the newly covered vaccines hepatitis B, Haemophilus influenzae type b...

Safety and efficacy of a cytomegalovirus glycoprotein B (gB) vaccine in adolescent girls: A randomized clinical trial.

PubMed

Bernstein, David I; Munoz, Flor M; Callahan, S Todd; Rupp, Richard; Wootton, Susan H; Edwards, Kathryn M; Turley, Christine B; Stanberry, Lawrence R; Patel, Shital M; Mcneal, Monica M; Pichon, Sylvie; Amegashie, Cyrille; Bellamy, Abbie R

2016-01-12

Cytomegalovirus (CMV) is a leading cause of congenital infection and an important target for vaccine development. CMV seronegative girls between 12 and 17 years of age received CMV glycoprotein B (gB) vaccine with MF59 or saline placebo at 0, 1 and 6 months. Blood and urine were collected throughout the study for evidence of CMV infection based on PCR and/or seroconversion to non-vaccine CMV antigens. 402 CMV seronegative subjects were vaccinated (195 vaccine, 207 placebo). The vaccine was generally well tolerated, although local and systemic adverse events were significantly more common in the vaccine group. The vaccine induced gB antibody in all vaccine recipients with a gB geometric mean titer of 13,400 EU; 95%CI 11,436, 15,700, after 3 doses. Overall, 48 CMV infections were detected (21 vaccine, 27 placebo). In the per protocol population (124 vaccine, 125 placebo) vaccine efficacy was 43%; 95%CI: -36; 76, p=0.20. The most significant difference was after 2 doses, administered as per protocol; vaccine efficacy 45%, 95%CI: -9; 72, p=0.08. The vaccine was safe and immunogenic. Although the efficacy did not reach conventional levels of significance, the results are consistent with a previous study in adult women (Pass et al. N Engl J Med 2009;360:1191) using the same formulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Field trial in commercial broilers with a multivalent in ovo vaccine comprising a mixture of live viral vaccines against Marek's disease, infectious bursal disease, Newcastle disease, and fowl pox.

PubMed

Sharma, J M; Zhang, Y; Jensen, D; Rautenschlein, Silke; Yeh, H Y

2002-01-01

A multivalent in ovo vaccine (MIV) was tested for safety and efficacy in a commercial broiler complex. The MIV comprised five replicating live viruses including serotypes 1, 2, and 3 of Marek's disease virus (MDV), an intermediate infectious bursal disease virus (IBDV) and a recombinant fowl poxvirus (FPV) vector vaccine containing HN and F genes of Newcastle disease virus (NDV). The performance of MIV-vaccinated broilers was compared with that of hatchmates that received turkey herpesvirus (HVT) alone (routinely used in ovo vaccine in the broiler complex). The chickens that hatched from the MIV-injected and HVT-injected eggs were raised under commercial conditions in six barns. Barn 1 housed 17,853 MIV-vaccinated chickens and each of the barns 2-6 housed 18,472-22,798 HVT-vaccinated chickens. The HVT-vaccinated chickens were given infectious bronchitis virus (IBV) and NDV vaccines at hatch and at 2 wk of age. The MIV-vaccinated chickens received IBV vaccine at hatch and IBV + NDV at 2 wk of age. The relative values of hatchability of eggs, livability and weight gain of chickens, and condemnation rates at processing were comparable between the MIV and the HVT groups (P > 0.05). Chickens from the MIV- and the HVT-vaccinated groups were challenged with virulent viruses under laboratory conditions. The resistance of vaccinated chickens against Marek's disease could not be assessed because of high natural resistance of unvaccinated commercial broilers to virulent MDV. The relative resistances of the MIV- and the HVT-vaccinated groups, respectively, against other virulent viruses were as follows: IBDV, 100% for both groups; NDV, 81% vs. 19%; FPV, 86% vs. 0%. The successful use of MIV under field conditions expands the usefulness of the in ovo technology for poultry.

Hepatitis B vaccine in celiac disease: yesterday, today and tomorrow.

PubMed

Vitaliti, Giovanna; Praticò, Andrea Domenico; Cimino, Carla; Di Dio, Giovanna; Lionetti, Elena; La Rosa, Mario; Leonardi, Salvatore

2013-02-14

Some studies showed that in celiac patients the immunological response to vaccination is similar to that one found in general population except for vaccine against hepatitis B virus (HBV). The non-responsiveness to HBV vaccine has also been described in healthy people, nevertheless the number of non-responders has been demonstrated to be higher in celiac disease (CD) patients than in healthy controls. Several hypothesis explaining this higher rate of unresponsiveness to HBV vaccine in CD patients have been described, such as the genetic hypothesis, according with CD patients carrying the disease-specific haplotype HLA-B8, DR3, and DQ2, show a lower response to HBV vaccine both in clinical expressed CD patients and in healthy people carrying the same haplotype. On the other hand, it has been demonstrated that the gluten intake during the vaccination seems to influence the response to the same vaccine. Moreover, it has been demonstrated a possible genetic predisposition to hepatitis B vaccine non-responsiveness likely due to the presence of specific human leukocyte antigen haplotypes and specific single nucleotide polymorphism in genes of cytokine/cytokine receptors and toll like receptors, but the pathogenic mechanism responsible for this low responsiveness still remains unclear. The aim of this review is to focus on the possible pathogenic causes of unresponsiveness to HBV vaccine in CD patients and to propose an alternative vaccination schedule in order to improve the responsiveness to HBV vaccine in this at-risk patients.

Safety and immunogenicity of a four-component meningococcal group B vaccine (4CMenB) and a quadrivalent meningococcal group ACWY conjugate vaccine administered concomitantly in healthy laboratory workers.

PubMed

Findlow, Jamie; Bai, Xilian; Findlow, Helen; Newton, Emma; Kaczmarski, Ed; Miller, Elizabeth; Borrow, Ray

2015-06-26

Safety precautions for laboratory staff working with meningococci should primarily rely on laboratory procedures preventing exposure to aerosols containing viable meningococci. Despite this, vaccination is a key component of protection in the occupational setting. In the UK in 2009, there were no licensed vaccines for meningococcal capsular group B or conjugate vaccines for capsular groups A, C, W and Y. We therefore undertook a Phase II trial in laboratory workers to investigate the safety and immunogenicity of a four component group B vaccine (4CMenB) and a quadrivalent group A, C, W and Y conjugate vaccine (ACWY-CRM). Enrolment was open to staff aged 18-65 years at the Public Health Laboratory, Manchester who may have had a potential occupational exposure risk to meningococci. 4CMenB was administered at 0, 2 and 6 months in the non-dominant arm and ACWY-CRM concomitantly at 0 months in the dominant arm. Pre- and post-vaccination blood samples were taken and analysed by the serum bactericidal antibody (SBA) assay against A, C, W and Y strains and a panel of seven diverse group B strains. Diary cards were used to record any local and systemic reactions following each vaccination. In total, 38 staff were enrolled and received initial vaccinations with 31 completing the trial per protocol. Both vaccines were proven safe, with local reactogenicity being more commonly reported following 4CMenB than ACWY-CRM. High proportions of subjects had putative protective SBA titres pre-vaccination, with 61-84 and 61-87% protected against A, C, W and Y strains and diverse MenB strains, respectively. Post-vaccination, SBA titres increased with 95-100 and 90-100% of subjects with protective SBA titres against A, C, W and Y strains and diverse MenB strains, respectively. These data suggest that 4CMenB and ACWY-CRM are safe when administered concomitantly and have the potential to enhance protection for laboratory workers. www.clinicaltrials.gov identifier: NCT00962624. Crown

Ab initio Study of Ag-Based Fluoroperovskite AgMF3 (M = Co and Ni) Compounds

NASA Astrophysics Data System (ADS)

Mubarak, A. A.

2018-01-01

Ab initio calculations of Ag-based fluoroperovskite AgMF3 (M = Co and Ni) compounds are investigated using the full-potential linearized augmented plane wave method. Wien2k and BoltzTrap codes are used to calculate the different physical properties. The structural parameters of the present compounds are within reasonable agreement with previous calculations. This study shows that AgCoF3 and AgNiF3 are anisotropic, ductile, mechanically and thermodynamically stable compounds, where AgCoF3 is found to be stiffer and less compressible than AgNiF3. The spin-polarized electronic band structure illustrates that AgCoF3 is metallic, while AgNiF3 is a semiconductor with indirect (M-D) band gap energy of 0.43 eV. The bonding force between atoms is found to be mainly ionic with some covalent nature. The total magnetic moment of AgCoF3 (3.04 μ B) is found to be higher than that calculated for AgNiF3 (2.00 μ B). Using the magnetic susceptibility calculations, AgCoF3 is classified as antiferromagnetic, whereas AgNiF3 is a ferromagnetic compound. The calculated static refractive index of AgCoF3 (3.85) and AgNiF3 (3.60) is inversely proportional with the energy band gap. Suitable applications are predicted for AgCoF3 and AgNiF3 based on their absorption and reflection properties. Furthermore, beneficial thermoelectric applications are expected for the present compounds due to their large Seebeck coefficient ( S_{{{{AgCoF}}_{ 3} }} = 2.92 × 103 μ {V/K} {and} S_{{{{AgNiF}}3 }} = 2.84 × 103 μ {V/K} ) and their thermoelectric power factor with respect to relaxation time ( S2 σ /t_{{AgNiF3 }} = 1.11 × 109 {W/K}^{ 2} {and} S2 σ /t_{{AgNiF3 }} = 1.28 × 10^{11} {W/K}^{ 2} ).

[Acute hepatitis A despite regular vaccination against hepatitis A and B].

PubMed

Junge, U; Melching, J; Dziuba, S

2002-07-26

A 59-year-old woman, her 55-year-old husband, their daughter, son and the son's girlfriend were admitted with acute icterus 32-34 days after a dinner when they had eaten shellfish. The father had been immunised against hepatitis A and B with a combined vaccine (Twinrix(R)) and had completed the full vaccination schedule 47 days prior to this meal. His wife had been incompletely vaccinated with one injection 16 days prior and a second injection 13 days after the dinner. The other three participants of the dinner had not been immunised. The incubation time and clinical picture did not differ between the vaccinated and non-vaccinated patients. All 5 patients were anti-HAV IgM-positive, had high serum aminotransferases and serum bilirubin. All patients had an uneventful recovery. There was no difference in the clinical course between the vaccinated and non-vaccinated patients. Combined hepatitis A/B vaccination according to the recommended schedule does not guarantee protection in elderly persons. Before travelling in endemic areas, their antibody response after basic hepatitis A/B vaccination should be determined.

[Designing of a candidate edible vaccine against hepatitis B and HIV on the basis of a transgenic tomato].

PubMed

Shchelkunov, S N; Saliaev, R K; Ryzhova, T S; Pozdniakov, S G; Nesterov, A E; Rekoslavskaia, N I; Sumtsova, V M; Pakova, N V; Mishutina, U O; Kopytina, T V; Hammond, R V

2004-01-01

The synthetic chimeric gene TBI-HBS encoding the synthesis of immunogenic ENV and GAC epitopes of HIV-1 (immunogenes of T- and B-lymphocytes) and of the surface protein (HBsAg) of the hepatitis B virus was introduced into tomato plants var. Ventura by agrobacterial vector pBIN35TBI-HBS; transgenic tomato plants with the integrated gene TBI-HBS were generated. The integration of the TBI-HBS target gene was confirmed by PCR. The synthesis of antigenic proteins of TBI and HBsAg in fruits of transgenic tomato plants was displayed by immunoassay. The fruits of transgenic tomato plants were fed to experimental mice with a 1-week interval. On days 14 and 28, there was discovered a sufficiently high content of antibodies to the antigenic proteins of HBV and HIV-1 in serum of experimental animals. Antibodies were found in feces of experimental mice; no antibodies were found in the control group of mice. Hence, it was established that the TBI (HIV-1) and HBsAg (HBV) antigens were synthesized in transgenic tomato fruits due to the integrated construction of pBINNp35TBI-HBS in an amount that was enough to induce the immunogenic response in mice to the oral delivery of edible vaccine.

[Prevention of serogroup B meningococcal disease using a four-component vaccine].

PubMed

Gil, A; Barranco, D; Batalla, J; Bayas, J M; Campins, M; Gorrotxategi Gorrotxategi, P; Lluch, J; Martinón-Torres, F; Mellado, M J; Moreno-Pérez, D; Uriel, B; Vázquez, J A

2014-04-01

Meningococcal disease is an infection caused by Neisseria meningitidis, and those of serogroup B are currently the most predominant. It has been difficult to create effective vaccines for this serogroup in order to modify or reduce its morbidity. The aim of this study was to review existing data on the new vaccine 4CMenB and its potential contribution to the prevention of this infection. A panel of 12 experts (from Pediatrics, Public Health and Vaccinology) conducted a literature search and prioritized 74 publications. A review of the vaccine was then prepared, which was discussed in a meeting and subsequently validated by e-mail. 4CMenB vaccine, based on four components (NadA, fHbp, NHBA and OMVnz), was designed by reverse vaccinology. The Meningococcal Antigen Typing System (MATS) shows a potential of 70-80% coverage of the strains in Europe. Clinical trials show that the vaccine is safe and immunogenic in infants, children, adolescents, and adults, and induces an anamnestic response. The incidence of fever is similar to systemic vaccines administered alone, but higher when co-administered with them, although the fever pattern is predictable and self-limited. It is compatible with the Spanish routine vaccines, and can be administered simultaneously with the currently available hexavalent and pentavalent vaccines, as well as the pneumococcal conjugate vaccine. The 4CMenB vaccine is the only strategy currently available to prevent meningococcal disease caused by serogroup B. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Hepatitis A and B immunity and vaccination in chronic hepatitis B and C patients in a large United States cohort.

PubMed

Henkle, Emily; Lu, Mei; Rupp, Lora B; Boscarino, Joseph A; Vijayadeva, Vinutha; Schmidt, Mark A; Gordon, Stuart C

2015-02-15

Hepatitis A and B vaccines are effective in preventing superinfection and sequelae in patients with chronic hepatitis B or C. We describe immunity and vaccination against hepatitis A and B in chronic hepatitis patients from the US Chronic Hepatitis Cohort Study. We identified chronic hepatitis B and C patients with healthcare utilization during 2006-2008 and 12 months of enrollment. We used electronic laboratory records to determine immunity and medical and billing records for vaccination history. Immunity against hepatitis A was defined by positive hepatitis A antibody or documented vaccination. Immunity against hepatitis B was defined as hepatitis B surface antibody level ≥10 mIU/mL or core antibody positive, or by documented vaccination. Among 1635 chronic hepatitis B patients, 978 (59.8%) were immune or vaccinated against hepatitis A, 122 (7.5%) had negative hepatitis A antibody tests, and 535 (32.7%) had no testing or vaccination record. Among 5328 chronic hepatitis C patients, 2998 (56.3%) were immune or vaccinated against hepatitis A, 659 (12.4%) had negative hepatitis A antibody tests, and 1671 (31.4%) had no testing or vaccination record. Additionally, 3150 (59.1%) chronic hepatitis C patients were immune or vaccinated against hepatitis B, 1003 (18.8%) had a negative test result, and 1175 (22.1%) were neither tested for nor vaccinated against hepatitis B. Approximately 40% of chronic hepatitis B and C patients are susceptible to or have no documented immunity or vaccination against hepatitis A or hepatitis B. Clinicians should consider antibody testing and vaccination for this vulnerable population. © The Author 2014. 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.

Meningococcal serogroup B vaccine: Knowledge and acceptability among parents in Italy

PubMed Central

Morrone, Teresa; Napolitano, Francesco; Albano, Luciana; Di Giuseppe, Gabriella

2017-01-01

ABSTRACT This study aimed to evaluate the knowledge and attitudes about Meningococcal meningitis B and the relative vaccine for children among a sample of parents in Italy. A cross-sectional investigation was conducted from October to December 2015 among a sample of 910 parents in the geographic area of Naples and Salerno (Italy). In total, 543 of 910 parents returned a completed questionnaire for a response rate of 59.7%. Almost all parents had heard about meningitis (95.8%), 79.8% of these knew the mode of transmission (through respiratory droplets) and 62.5% knew the susceptible population (infants, children and adolescents). Moreover, a large percentage (86%) knew that the vaccine is a preventive measure. Parents who were married, those who had one child, those who did not have information about the MenB vaccine by physicians and those who needed additional information about the MenB vaccine were more likely to know the vaccine as a preventive measure of meningitis. Regarding attitudes toward the MenB vaccine, approximately two thirds of parents considered the vaccine useful (67.2%) and said that they would vaccinate their children (64.1%). Parents who had administered at least one recommended vaccination to their children, those who considered the vaccine useful, those with need for additional information about the vaccine and those who knew that the vaccine was a preventive measure of meningitis were more likely to have a positive attitude to vaccinating their children. Considering the results of our study, it looks appropriate that the knowledge of the population about meningitis and its related vaccinations is improved through correct health education and effective vaccine strategies that are implemented by policy makers. PMID:28441109

Serogroup B Meningococcal vaccine (MenB) - What you need to know

MedlinePlus

... disabilities such as hearing loss, brain damage, kidney damage, amputations, nervous system problems, or severe scars from skin grafts. Serogroup B meningococcal (MenB) vaccines can help prevent meningococcal disease caused by serogroup ...

42 CFR 410.63 - Hepatitis B vaccine and blood clotting factors: Conditions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Hepatitis B vaccine and blood clotting factors... Other Health Services § 410.63 Hepatitis B vaccine and blood clotting factors: Conditions... under § 410.10, subject to the specified conditions: (a) Hepatitis B vaccine: Conditions. Effective...

Dynamic of Immune Response induced in Hepatitis B Surface Antigen-transgenic Mice Immunized with a Novel Therapeutic Formulation

PubMed Central

Almeida, Freya M Freyre; Blanco, Aracelys; Trujillo, Heidy; Hernández, Dunia; García, Daymir; Alba, José S; Abad, Matilde López; Merino, Nelson; Lobaina, Yadira

2016-01-01

ABSTRACT The development of therapeutic vaccines against chronic hepatitis B requires the capacity of the formulation to subvert a tolerated immune response as well as the evaluation of histopathological damage resulting from the treatment. In the present study, the dynamicity of induced immune response to hepatitis B surface antigen (HBsAg) was evaluated in transgenic mice that constitutively express the HBsAg gene (HBsAg-tg mice). After immunization with a vaccine candidate containing both surface (HBsAg) and core (HBcAg) antigens of hepatitis B virus (HBV), the effect of vaccination on clearance of circulating HBsAg and the potential histological alterations were examined. Transgenic (tg) and non-transgenic (Ntg) mice were immunized by intranasal (IN) and subcutaneous (SC) routes simultaneously. A control group received phosphate-buffered saline (PBS) by IN route and aluminum by SC route. Positive responses, at both humoral and cellular levels, were obtained after five immunizations in HBsAg-tg mice. Such responses were delayed and of lower intensity in tg mice, compared to vaccinated Ntg mice. Serum IgG response was characterized by a similar IgG subclass pattern. Even when HBsAg-specific CD8+ T cell responses were clearly detectable by gamma-interferon ELISPOT assay, histopathological alterations were not detected in any organ, including the liver and kidneys. Our study demonstrated, that it is possible to subvert the immune tolerance against HBsAg in tg mice, opening a window for new studies to optimize the schedule, dose, and formulation to improve the immune response to the therapeutic vaccine candidate. These results can be considered a safety proof to support clinical developments for the formulation under study. How to cite this article Freyre FM, Blanco A, Trujillo H, Hernández D, García D, Alba JS, Lopez M, Merino N, Lobaina Y, Aguilar JC. Dynamic of Immune Response induced in Hepatitis B Surface Antigen-transgenic Mice Immunized with a Novel

Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: a randomised open-label trial (OSST trial).

PubMed

Ning, Qin; Han, Meifang; Sun, Yongtao; Jiang, Jiaji; Tan, Deming; Hou, Jinlin; Tang, Hong; Sheng, Jifang; Zhao, Mianzhi

2014-10-01

Durable post-treatment response is uncommon in chronic hepatitis B (CHB) patients on nucleos(t)ide analogue therapy. Response, response predictors and safety were assessed in patients who switched from long-term entecavir (ETV) to peginterferon alfa-2a. Hepatitis B e antigen (HBeAg)-positive CHB patients who had received ETV for 9-36 months, with HBeAg <100 PEIU/ml and HBV DNA ⩽1000 copies/ml, were randomised 1:1 to receive peginterferon alfa-2a 180 μg/week or ETV 0.5mg/day for 48 weeks. The primary endpoint was HBeAg seroconversion at week 48 (ClinicalTrials.gov: NCT00940485). 200 patients were randomised; 197 received ⩾1 study drug dose. Five patients who were anti-HBe-positive at baseline were excluded from the modified intention-to-treat population (peginterferon alfa-2a, n = 94; ETV, n = 98). Patients who switched to peginterferon alfa-2a achieved higher week 48 HBeAg seroconversion rates vs. those who continued ETV (14.9% vs. 6.1%; p = 0.0467). Only patients receiving peginterferon alfa-2a achieved HBsAg loss (8.5%). Among peginterferon alfa-2a-treated patients with HBeAg loss and HBsAg <1500 IU/ml at randomisation, 33.3% and 22.2% achieved HBeAg seroconversion and HBsAg loss, respectively. Early on-treatment HBsAg decline predicted response at week 48; highest rates were observed in patients with week 12 HBsAg <200 IU/ml (HBeAg seroconversion, 66.7%; HBsAg loss, 77.8%). Alanine aminotransferase elevations were not associated with viral rebound (n = 38). Peginterferon alfa-2a was well-tolerated. For patients who achieve virological suppression with ETV, switching to a finite course of peginterferon alfa-2a significantly increases rates of HBeAg seroconversion and HBsAg loss. A response-guided approach may identify patients with the greatest chance of success. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The tuberculosis vaccine H4:IC31 is safe and induces a persistent polyfunctional CD4 T cell response in South African adults: A randomized controlled trial.

PubMed

Geldenhuys, Hennie; Mearns, Helen; Miles, David J C; Tameris, Michele; Hokey, David; Shi, Zhongkai; Bennett, Sean; Andersen, Peter; Kromann, Ingrid; Hoff, Søren T; Hanekom, Willem A; Mahomed, Hassan; Hatherill, Mark; Scriba, Thomas J; van Rooyen, Michele; Bruce McClain, J; Ryall, Robert; de Bruyn, Guy

2015-07-09

New, more effective vaccines to prevent tuberculosis (TB) disease are needed urgently. H4:IC31 is an investigational vaccine that contains a fusion protein of the immunodominant antigens TB10.4 and Ag85B, formulated in IC31 adjuvant. We assessed the safety and immunogenicity of H4:IC31 in South African adults from a TB endemic setting. In this double blind, placebo controlled, phase I trial, Mycobacterium tuberculosis-uninfected, HIV-uninfected, healthy adults with a history of childhood BCG vaccination were randomly allocated to two intramuscular vaccinations with 5, 15, 50 or 150 μg H4 formulated in 500nmol IC31, two months apart. Vaccinees were followed for six months to assess safety; immunogenicity was measured by ELISpot and intracellular cytokine staining assays. Thirty-two participants received H4:IC31 and 8 received placebo. Injection site adverse events were common but mild; mild fatigue was the most common systemic adverse event. Frequencies of adverse events did not differ between dosage groups. Detectable antigen-specific CD4 T cell responses were induced by all doses of H4:IC31, but doses below 50 μg induced the highest frequencies of CD4 T cells, comprised predominantly of IFN-γ(+)TNF-α(+)IL-2(+) or TNF-α(+)IL-2(+) cells. These memory responses persisted up to the end of follow up, on study day 182. H4:IC31 demonstrated an acceptable safety profile and was immunogenic in South African adults. In this trial, the 15 μg dose appeared to induce the most optimal immune response. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Pharmacovigilance of hepatitis B vaccines].

PubMed

Imbs, Jean-Louis; Decker, Nicole; Welsch, Marie

2003-01-01

Since the hepatitis B vaccine are on the market in France, until the end of 2002, 1211 observations of demyelinating disease of the central nervous system (1109 cases of which 895 multiple sclerosis) or peripheral (102 cases of which 49 Guillain Barre Syndrome), have been reported to the french network of pharmacovigilance and to the AFSSAPS. It is not possible to singularize these observations, neither from a clinical nor an epidemiological point of view. No risk factor has been detected. Only the chronology could suggest a causal relationship, the vaccine preceding the pathology in all the cases notified.

Vaccine draining lymph nodes are a source of antigen-specific B cells.

PubMed

Pero, Stephanie C; Sun, Yu-Jing; Shukla, Girja S; Carman, Chelsea L; Krag, Christopher C; Teuscher, Cory; Krementsov, Dimitry N; Krag, David N

2017-03-01

Our research is focused on using vaccine draining lymph nodes as a source of immune cells to better understand the immune response and to attempt to generate new anti-cancer reagents. Following a vaccine, harvesting the lymph node can only be done once. We endeavored to determine the range of times that B cells secreting anti-KLH antibodies were present in the node of KLH-vaccinated mice. Following vaccination the total number of mononuclear cells (MNCs) increased in the vaccine-draining lymph node (VDN). The percentage of MNCs that were B cells nearly doubled. B cells recovered from the node that secreted anti-KLH antibodies were evident by day 7. The number continued to increase and then slowly decreased over the observed time range to 28days after vaccination. The VDN, compared to the spleen, the bone marrow and the nonVDN, contained a higher percentage of B cells that secreted anti-KLH antibodies. After a vaccine, there is a multi-week window of time when an increasing number of B cells are present in a VDN that secrete anti-KLH antibodies. These results support using the VDN as a source for B cells that secrete anti-vaccine antibodies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antigen-specific B memory cell responses to lipopolysaccharide (LPS) and invasion plasmid antigen (Ipa) B elicited in volunteers vaccinated with live-attenuated Shigella flexneri 2a vaccine candidates.

PubMed

Simon, J K; Wahid, R; Maciel, M; Picking, W L; Kotloff, K L; Levine, M M; Sztein, M B

2009-01-22

We evaluated B memory responses in healthy adult volunteers who received one oral dose of live-attenuated Shigella flexneri 2a vaccine. LPS-specific B(M) cells increased from a median of 0 at baseline to 20 spot forming cells (SFC)/10(6) expanded cells following vaccination (p=0.008). A strong correlation was found between post-vaccination anti-LPS B(M) cell counts and peak serum anti-LPS IgG titers (rs=0.95, p=0.0003). Increases in B(M) specific for IpaB approaching significance were also observed. In sum, oral vaccination with live-attenuated S. flexneri 2a elicits B(M) cells to LPS and IpaB, suggesting that B(M) responses to Shigella antigens should be further studied as a suitable surrogate of protection in shigellosis.

Sero-prevalence and vaccination status of hepatitis A and hepatitis B among adults with cirrhosis in Sri Lanka: a hospital based cohort study.

PubMed

Niriella, Madunil Anuk; Kobbegala, Vipuli Jayendra; Karalliyadda, Hasnatha Nuwan; Ranawaka, Chamila Kumara; de Silva, Arjuna Priyadarshin; Dassanayake, Anuradha Supun; de Silva, Hithanadura Janaka

2017-07-21

As acute viral hepatitis can be fatal in patients with cirrhosis, vaccination against hepatitis A (HAV) and hepatitis B (HBV) is recommended for non-immune patients. With increasing affluence the incidence of hepatitis A in childhood has decreased leading to a significant proportion of non-immune adults. As part of their routine investigation, hepatitis A IgG antibodies (anti-HAV IgG), hepatitis B surface antigen (HBsAg) and anti-HCV antibodies was checked and immunization status was assessed among consenting newly diagnosed cirrhotic patients presenting to a tertiary referral center. Out of 135 patients, 107 [79.3%; males 91; mean age (SD) at presentation: 55.5 (11.6) years] with complete data were included for analysis. Most patients had either cryptogenic cirrhosis (62.6%) or alcoholic cirrhosis (29.9%); 2 (1.9%) had HBV cirrhosis, none had hepatitis C (HCV) cirrhosis. None of the patients had received vaccination against hepatitis A, while 71 (67.6%) had been vaccinated against HBV. The majority [62 (58%)] were negative for anti-HAV IgG. Most cirrhotic patients in this cohort were not immune to hepatitis A. None had been vaccinated against HAV, while a third of patients had not been vaccinated against HBV. Cirrhotic patients should be routinely investigated for immunity against HAV and HBV, and vaccination offered to those found to be non-immune.

Subunit vaccine H56/CAF01 induces a population of circulating CD4 T cells that traffic into the Mycobacterium tuberculosis-infected lung.

PubMed

Woodworth, J S; Cohen, S B; Moguche, A O; Plumlee, C R; Agger, E M; Urdahl, K B; Andersen, P

2017-03-01

The capacity of CD4 T cells to protect against Mycobacterium tuberculosis (Mtb) is governed by their ability to localize to the lung site of infection. Subunit vaccine H56/CAF01, a liposome-adjuvanted fusion protein of Mtb antigens Ag85B, ESAT-6, and Rv2660, conferred durable protection and elicited polyfunctional CD4 T cells that preferentially localized to the lung parenchyma. These lung-resident T cells had reduced KLRG1 and increased CXCR3 expression, an intermediate state of Th1 differentiation that has been associated with Mtb protection. Importantly, KLGR1 - CXCR3 + cells were also enriched in the lung vasculature and peripheral circulation of vaccinated animals, but not controls. Moreover, S1P1R blockade rapidly cleared this population from the blood and adoptive transfer of T cells recovered from the vasculature of vaccinated, but not control, mice efficiently trafficked into the Mtb-infected lung parenchyma. Thus, durable immunity elicited by H56/CAF01 vaccination is associated with the maintenance of circulating CD4 T cells that selectively home to the lung parenchyma.

Immunogenicity and safety of an investigational multicomponent, recombinant, meningococcal serogroup B vaccine (4CMenB) administered concomitantly with routine infant and child vaccinations: results of two randomised trials.

PubMed

Vesikari, Timo; Esposito, Susanna; Prymula, Roman; Ypma, Ellen; Kohl, Igor; Toneatto, Daniela; Dull, Peter; Kimura, Alan

2013-03-09

Meningococcal serogroup B disease disproportionately affects infants. We assessed lot-to-lot consistency, safety and immunogenicity, and the effect of concomitant vaccination on responses to routine vaccines of an investigational multicomponent vaccine (4CMenB) in this population. We did primary and booster phase 3 studies between March 31, 2008, and Aug 16, 2010, in 70 sites in Europe. We used two series of sponsor-supplied, computer-generated randomisation envelopes to allocate healthy 2 month-old infants to receive routine vaccinations (diphtheria-tetanus-acellular pertussis, inactivated poliovirus, hepatitis B plus Haemophilus influenzae type b, and seven-valent pneumococcal vaccine) at 2, 4, and 6 months of age alone, or concomitantly with 4CMenB or serogroup C conjugate vaccine (MenC) in: 1) an open-label, lot-to-lot immunogenicity and safety substudy of three 4CMenB lots compared with routine vaccines alone (1:1:1:1, block size eight); or 2) an observer-blind, lot-to-lot safety substudy of three 4CMenB lots compared with MenC (1:1:1:3, block size six). At 12 months, 4CMenB-primed children from either substudy were randomised (1:1, block size two) to receive 4CMenB booster, with or without measles-mumps-rubella-varicella (MMRV) vaccine. Immunogenicity was assessed by serum bactericidal assay with human complement (hSBA) against serogroup B test strains, and on randomly selected subsets of serum samples for routine vaccines; laboratory personnel were masked to assignment. The first coprimary outcome was lot-to-lot consistency (hSBA geometric mean ratio of all lots between 0·5 and 2·0), and the second was an immune response (hSBA titre ≥5) for each of the three strains. The primary outcome for the booster study was immune response to booster dose. Immunogenicity data for 4CMenB were for the modified intention-to-treat population, including all infants from the open-label substudy who provided serum samples. The safety population included all participants

What shapes vaccine policy? The case of hepatitis B in the UK.

PubMed

Stanton, J

1994-12-01

Comparison of hepatitis B vaccine policy with other cases in the past is complicated by the restricted modes of transmission of this disease, which affects relatively few people in the UK. Still, considerations of cost, fear of contamination, divisions of opinion within the medical profession, and regional dispersal of authority are all factors--analysed for other vaccines--which help to explain the limited UK central policy on hepatitis B immunization observed through the 1980s. An important issue, in previous debates on vaccine policies, has been the conflict between public health interests and the rights of individuals to eschew health interventions imposed by the state. It is argued here that this question fed into hepatitis B vaccine policy in an oblique manner, via policy on screening for hepatitis B in the 1970s; minimal screening mainly of selected groups of health workers was favoured, maximizing individual rights. Changes to hepatitis B vaccine policy can be traced, linked with international policy, pharmaceutical company pressure, advances in vaccine technology, and questions of legal liability. The most accurate predictor for vaccine policy appears to have been screening policy. Will this apply to AIDS, which is epidemiologically similar to hepatitis B?

Analysis of hepatitis B vaccination behavior and vaccination willingness among migrant workers from rural China based on protection motivation theory

PubMed Central

Liu, Rugang; Li, Youwei; Wangen, Knut R.; Maitland, Elizabeth; Nicholas, Stephen; Wang, Jian

2016-01-01

ABSTRACT Introduction: With China's accelerating urbanization, migrant workers comprise up to 40% of the urban population of China's largest cities. More mobile than non-migrant urban dwellers, migrants are more likely to contract and spread hepatitis B (HB) than non-migrants. Due to the mandatory system of household registration (hukou), migrants are less likely to be covered by national HB immunization programs and also to have more limited access to public health services where they work than non-migrants. Migrants form a significant sub-group in all Chinese cities posing unique public policy vaccination challenges. Objective: Using protection motivation theory (PMT), we developed and measured HB cognitive variables and analyze the factors affecting HB vaccination behavior and willingness to vaccinate by migrant workers. We propose public policy interventions to increase HB vaccination rates of migrant workers. Methods: We developed a questionnaire to collect information on the HB vaccination characteristics of 1684 respondents from 6 provinces and Beijing. Exploratory factor analysis was used to create PMT variables and a binary logistic regression model was used to analyze the factors affecting migrant workers' HB vaccination behavior and willingness to vaccinate. Results: Vulnerability and response-efficacy were significant PMT cognition factors determining HB vaccination behavior. The HB vaccination rate for migrants decreased with increasing age and was smaller for the primary education than the high education group. The vaccination rate of the medical insurance group was significantly greater than the non-insured group, and the vaccination probability was significantly higher for the self-rated good health compared to the self-rated poor health group. Geographical birth location mattered: the vaccination rate for Beijing city and Ningxia province migrants were higher than for Hebei province and the vaccination rate was lower for migrants born far from

Analysis of hepatitis B vaccination behavior and vaccination willingness among migrant workers from rural China based on protection motivation theory.

PubMed

Liu, Rugang; Li, Youwei; Wangen, Knut R; Maitland, Elizabeth; Nicholas, Stephen; Wang, Jian

2016-05-03

With China's accelerating urbanization, migrant workers comprise up to 40% of the urban population of China's largest cities. More mobile than non-migrant urban dwellers, migrants are more likely to contract and spread hepatitis B (HB) than non-migrants. Due to the mandatory system of household registration (hukou), migrants are less likely to be covered by national HB immunization programs and also to have more limited access to public health services where they work than non-migrants. Migrants form a significant sub-group in all Chinese cities posing unique public policy vaccination challenges. Using protection motivation theory (PMT), we developed and measured HB cognitive variables and analyze the factors affecting HB vaccination behavior and willingness to vaccinate by migrant workers. We propose public policy interventions to increase HB vaccination rates of migrant workers. We developed a questionnaire to collect information on the HB vaccination characteristics of 1684 respondents from 6 provinces and Beijing. Exploratory factor analysis was used to create PMT variables and a binary logistic regression model was used to analyze the factors affecting migrant workers' HB vaccination behavior and willingness to vaccinate. Vulnerability and response-efficacy were significant PMT cognition factors determining HB vaccination behavior. The HB vaccination rate for migrants decreased with increasing age and was smaller for the primary education than the high education group. The vaccination rate of the medical insurance group was significantly greater than the non-insured group, and the vaccination probability was significantly higher for the self-rated good health compared to the self-rated poor health group. Geographical birth location mattered: the vaccination rate for Beijing city and Ningxia province migrants were higher than for Hebei province and the vaccination rate was lower for migrants born far from health facilities compared to those located middle

Mycobacterium tuberculosis PstS1 amplifies IFN-γ and induces IL-17/IL-22 responses by unrelated memory CD4+ T cells via dendritic cell activation.

PubMed

Palma, Carla; Schiavoni, Giovanna; Abalsamo, Laura; Mattei, Fabrizio; Piccaro, Giovanni; Sanchez, Massimo; Fernandez, Carmen; Singh, Mahavir; Gabriele, Lucia

2013-09-01

The immunological mechanisms that modulate protection during Mycobacterium tuberculosis (Mtb) infection or vaccination are not fully understood. Secretion of IFN-γ and, to a lesser extent, of IL-17 by CD4(+) T cells plays a major role both in protection and immunopathology. Few Mtb Ags interacting with DCs affect priming, activation, and regulation of Ag-unrelated CD4(+) T-cell responses. Here we demonstrate that PstS1, a 38 kDa-lipoprotein of Mtb, promotes Ag-independent activation of memory T lymphocytes specific for Ag85B or Ag85A, two immunodominant protective Ags of Mtb. PstS1 expands CD4(+) and CD8(+) memory T cells, amplifies secretion of IFN-γ and IL-22 and induces IL-17 production by effector memory cells in an Ag-unrelated manner in vitro and in vivo. These effects were mediated through the stimulation of DCs, particularly of the CD8α(-) subtype, which respond to PstS1 by undergoing phenotypic maturation and by secreting IL-6, IL-1β and, to a lower extent, IL-23. IL-6 secretion by PstS1-stimulated DCs was required for IFN-γ, and to a lesser extent for IL-22 responses by Ag85B-specific memory T cells. These results may open new perspectives for immunotherapeutic strategies to control Th1/Th17 immune responses in Mtb infections and in vaccinations against tuberculosis. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Poly-ϵ-caprolactone/chitosan nanoparticles provide strong adjuvant effect for hepatitis B antigen.

PubMed

Jesus, Sandra; Soares, Edna; Borchard, Gerrit; Borges, Olga

2017-10-01

This work aims to investigate the adjuvant effect of poly-ϵ-caprolactone/chitosan nanoparticles (NPs) for hepatitis B surface antigen (HBsAg) and the plasmid DNA encoding HBsAg (pRC/CMV-HBs). Both antigens were adsorbed onto preformed NPs. Vaccination studies were performed in C57BL/6 mice. Transfection efficiency was investigated in A549 cell line. HBsAg-adsorbed NPs generated strong anti-HBsAg IgG titers, mainly of IgG1 isotype, and induced antigen-specific IFN-γ and IL-17 secretion by spleen cells. The addition of pRC/CMV-HBs to the HBsAg-adsorbed NPs inhibited IL-17 secretion but had minor effect on IFN-γ levels. Lastly, pRC/CMV-HBs-loaded NPs generated a weak serum antibody response. Poly-ϵ-caprolactone/chitosan NPs provide a strong humoral adjuvant effect for HBsAg and induce a Th1/Th17-mediated cellular immune responses worth explore for hepatitis B virus vaccination.

Skin vaccination via fractional infrared laser ablation - Optimization of laser-parameters and adjuvantation.

PubMed

Scheiblhofer, Sandra; Strobl, Anna; Hoepflinger, Veronika; Thalhamer, Theresa; Steiner, Martin; Thalhamer, Josef; Weiss, Richard

2017-03-27

Methods to deliver an antigen into the skin in a painless, defined, and reproducible manner are essential for transcutaneous immunization (TCI). Here, we employed an ablative fractional infrared laser (P.L.E.A.S.E. Professional) to introduce clinically relevant vaccines into the skin. To elicit the highest possible antibody titers with this system, we optimized different laser parameters, such as fluence and pore number per area, and tested various adjuvants. BALB/c mice were immunized with Hepatitis B surface antigen (HBsAg) by laser-microporation. Adjuvants used were alum, CRM 197 , monophosphoryl lipid A, heat-labile enterotoxin subunit B of E. coli (LT-B), and CpG ODN1826. The influence of different fluences (2.1 to 16.8J/cm 2 ) and pore densities (5-15%) was investigated. Furthermore, immunogenicity of HBsAg and the commercially available conjugate vaccines ActHIB® and Menveo® applied via TCI was compared to standard i.m. injection. Antigen-specific antibody titers were assessed by luminometric ELISA. Antibody titers against HBsAg were dependent on pore depth and peaked at a fluence of 8.4J/cm 2 . Immunogenicity was independent of pore density. Adjuvantation with alum significantly reduced antibody titers after TCI, whereas other adjuvants only induced marginal changes in total IgG titers. LT-B and CpG shifted the polarization of the immune response as indicated by decreased IgG1/IgG2a ratios. HBsAg/LT-B applied via TCI induced similar antibody titers compared to i.m. injection of HBsAg/alum. In contrast to i.m. injection, we observed a dose response from 5 to 20μg after TCI. Both, ActHIB® and Menveo® induced high antibody titers after TCI, which were comparable to i.m. injection. Alum, the most commonly used adjuvant, is contraindicated for transcutaneous vaccination via laser-generated micropores. TCI with optimized laser parameters induces high antibody titers, which cannot be significantly increased by the tested adjuvants. Commercially available

Peginterferon alfa-2b in the treatment of Chinese patients with HBeAg-positive chronic hepatitis B: a randomized trial.

PubMed

Cheng, Jun; Wang, Yuming; Hou, Jinlin; Luo, Duande; Xie, Qing; Ning, Qin; Ren, Hong; Ding, Huiguo; Sheng, Jifang; Wei, Lai; Chen, Shijun; Fan, Xiaoling; Huang, Wenxiang; Pan, Chen; Gao, Zhiliang; Zhang, Jiming; Zhou, Boping; Chen, Guofeng; Wan, Mobin; Tang, Hong; Wang, Guiqiang; Yang, Yuxiu; Mohamed, Rosmawati; Guan, Richard; Lee, Tzong-Hsi; Chang, Wen-Hsiung; Zhenfei, Huang; Ye, Zhang; Xu, Daozhen

2014-12-01

In mainland China, peginterferon (PEG-IFN) alfa-2b 1.0μg/kg/wk for 24 weeks is the approved treatment for HBeAg-positive chronic hepatitis B. This multicenter, randomized trial evaluated the safety and efficacy of regimens utilizing increased dose or treatment duration in treatment-naive Chinese patients with chronic hepatitis B. 670 HBeAg-positive patients from China, Malaysia, Taiwan area, Singapore, and Thailand were enrolled. Patients received PEG-IFN alfa-2b 1.0μg/kg/wk (arm A) or 1.5μg/kg/wk (arm B) for 24 weeks, or 1.5μg/kg/wk for 48 weeks (arm C). The primary end point was loss of HBeAg 24 weeks after end of treatment. At the end of follow-up, HBeAg loss was significantly greater in arm C compared with arm A (31.3% vs. 17.3%; P=0.001) and arm B (31.3% vs. 18.1%; P=0.001). No significant difference in the rate of HBeAg loss was observed between arms A and B. The proportions of patients with HBe seroconversion, HBV DNA levels <20,000IU/mL, and ALT normalization at the end of follow-up were significantly higher in arm C compared with arm A and arm B. In arms A, B, and C, rates of early treatment discontinuation were 6.3%, 4.9%, and 8.9%; of discontinuation due to an AE, 2%, 3%, and 3%; and of AEs requiring dose modification, 3%, 6%, and 10%, respectively. In Chinese patients with HBeAg-positive chronic hepatitis B, PEG-IFN alfa-2b 1.5μg/kg/wk for 48 weeks is more efficacious compared with 1.0 and 1.5μg/kg/wk for 24 weeks. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Peginterferon lambda for the treatment of HBeAg-positive chronic hepatitis B: A randomized phase 2b study (LIRA-B).

PubMed

Chan, Henry L Y; Ahn, Sang Hoon; Chang, Ting-Tsung; Peng, Cheng-Yuan; Wong, David; Coffin, Carla S; Lim, Seng Gee; Chen, Pei-Jer; Janssen, Harry L A; Marcellin, Patrick; Serfaty, Lawrence; Zeuzem, Stefan; Cohen, David; Critelli, Linda; Xu, Dong; Wind-Rotolo, Megan; Cooney, Elizabeth

2016-05-01

Peginterferon lambda-1a (lambda) is a Type-III interferon, which, like alfa interferons, has antiviral activity in vitro against hepatitis B virus (HBV) and hepatitis C virus (HCV); however, lambda has a more limited extra-hepatic receptor distribution. This phase 2b study (LIRA-B) evaluated lambda in patients with chronic HBV infection. Adult HBeAg+ interferon-naive patients were randomized (1:1) to weekly lambda (180 μg) or peginterferon alfa-2a (alfa) for 48 weeks. The primary efficacy endpoint was HBeAg seroconversion at week 24 post-treatment; lambda non-inferiority was demonstrated if the 80% confidence interval (80% CI) lower bound was >-15%. Baseline characteristics were balanced across groups (lambda N=80; alfa N=83). Early on-treatment declines in HBV-DNA and qHBsAg through week 24 were greater with lambda. HBeAg seroconversion rates were comparable for lambda and alfa at week 48 (17.5% vs. 16.9%, respectively); however lambda non-inferiority was not met at week 24 post-treatment (13.8% vs. 30.1%, respectively; lambda vs. alfa 80% CI lower bound -24%). Results for other key secondary endpoints (virologic, serologic, biochemical) and post hoc combined endpoints (HBV-DNA <2000 IU/ml plus HBeAg seroconversion or ALT normalization) mostly favored alfa. Overall adverse events (AE), serious AE, and AE-discontinuation rates were comparable between arms but AE-spectra differed (more cytopenias, flu-like, and musculoskeletal symptoms observed with alfa, more ALT flares and bilirubin elevations seen with lambda). Most on-treatment flares occurred early (weeks 4-12), associated with HBV-DNA decline; all post-treatment flares were preceded by HBV-DNA rise. On-treatment, lambda showed greater early effects on HBV-DNA and qHBsAg, and comparable serologic/virologic responses at end-of-treatment. However, post-treatment, alfa-associated HBeAg seroconversion rates were higher, and key secondary results mostly favored alfa. ClinicalTrials.gov number: NCT01204762

Randomized controlled trial of concurrent hepatitis A and B vaccination.

PubMed

Bryan, J P; McCardle, P; South-Paul, J E; Fogarty, J P; Legters, L J; Perine, P L

2001-02-01

Hepatitis A and B viruses are threats to deployed military forces. The objective of this study was to determine the feasibility of concurrent vaccination against hepatitis A and B viruses. One hundred five healthy persons, 20 to 49 years of age and without serologic markers to hepatitis A or B viruses, were randomized to receive an inactivated hepatitis A vaccine (HEP A; 25 units in 0.5 mL), recombinant hepatitis B vaccine (HEP B; 10 micrograms in 1.0 mL), or both (HEP A & B) concurrently in separate arms. Vaccines were administered intramuscularly at 0, 1, and 6 months. Sera obtained at 1, 2, 6, 7, and 12 months after the first dose were tested for quantitative antibody to hepatitis A virus (anti-HAV) and antibody to hepatitis B surface antigen. Local reactions (e.g., pain) were reported by less than half of the volunteers and were similar at the site of HEP A, whether given alone or concurrently. However, more persons complained of pain (usually mild) at the HEP B site when HEP B was given concurrently with HEP A compared with HEP B alone (43% vs. 15%, 34% vs. 9%, and 42% vs. 15% for doses 1, 2, and 3, respectively; p < 0.05 for each dose). Among persons immunized with HEP A alone or HEP A & B, the proportion with > or = 10 mIU/mL anti-HAV was 83% in both groups 1 month after dose 1 and 100% at months 2, 7, and 12. The geometric mean concentrations of anti-HAV increased from 21 mIU/mL at month 1 to 2,649 and 2,312 mIU/mL in the HEP A and HEP A & B groups, respectively, at month 7. The response to HEP B was similar whether administered alone or concurrently. Antibody responses were similar in those receiving HEP A or HEP B concurrently or alone, but more subjects reported pain (usually mild) at the HEP B site after concurrent vaccination than after HEP B alone. Further work should be conducted to approve HEP A for patients younger than 2 years of age and to develop combined HEP A and HEP B vaccines in the United States.

Freeze-Drying of Plant Tissue Containing HBV Surface Antigen for the Oral Vaccine against Hepatitis B

PubMed Central

Milczarek, Magdalena; Pajtasz-Piasecka, Elżbieta; Wietrzyk, Joanna

2014-01-01

The aim of this study was to develop a freeze-drying protocol facilitating successful processing of plant material containing the small surface antigen of hepatitis B virus (S-HBsAg) while preserving its VLP structure and immunogenicity. Freeze-drying of the antigen in lettuce leaf tissue, without any isolation or purification step, was investigated. Each process step was consecutively evaluated and the best parameters were applied. Several drying profiles and excipients were tested. The profile of 20°C for 20 h for primary and 22°C for 2 h for secondary drying as well as sucrose expressed efficient stabilisation of S-HBsAg during freeze-drying. Freezing rate and postprocess residual moisture were also analysed as important factors affecting S-HBsAg preservation. The process was reproducible and provided a product with VLP content up to 200 µg/g DW. Assays for VLPs and total antigen together with animal immunisation trials confirmed preservation of antigenicity and immunogenicity of S-HBsAg in freeze-dried powder. Long-term stability tests revealed that the stored freeze-dried product was stable at 4°C for one year, but degraded at elevated temperatures. As a result, a basis for an efficient freeze-drying process has been established and a suitable semiproduct for oral plant-derived vaccine against HBV was obtained. PMID:25371900

Cost-effectiveness of hepatitis B vaccination of prison inmates.

PubMed

Pisu, Maria; Meltzer, Martin Isaac; Lyerla, Rob

2002-12-13

The purpose of this paper is to determine the cost-effectiveness of vaccinating inmates against hepatitis B. From the prison perspective, vaccinating inmates at intake is not cost-saving. It could be economically beneficial when the cost of a vaccine dose is 1.6 and 50%, respectively. The health care system realizes net savings even when there is no incidence in prison, or there is no cost of chronic liver disease, or when only one dose of vaccine is administered. Thus, while prisons might not have economic incentives to implement hepatitis B vaccination programs, the health care system would benefit from allocating resources to them.

Safety and immunogenicity of a booster dose of a 3-antigen Staphylococcus aureus vaccine (SA3Ag) in healthy adults: A randomized phase 1 study.

PubMed

Marshall, Helen; Nissen, Michael; Richmond, Peter; Shakib, Sepehr; Jiang, Qin; Cooper, David; Rill, Denise; Baber, James; Eiden, Joseph; Gruber, William C; Jansen, Kathrin U; Anderson, Annaliesa S; Zito, Edward T; Girgenti, Douglas

2016-11-01

A 2-stage, phase 1, randomized, placebo-controlled study in healthy adults to assess immunogenicity and safety of a booster dose at three dose levels of a 3-antigen Staphylococcus aureus vaccine (SA3Ag) containing recombinant clumping factor A (ClfA) and capsular polysaccharides 5 and 8 (CP5 and CP8) conjugated to a diphtheria toxoid. Six months after initial single vaccination, in Stage 2, SA3Ag recipients were randomized (1:1) to booster vaccination or placebo, while Stage 1 placebo recipients received placebo again. Pre- and post-vaccination blood samples were analyzed. In Stage 2 (n = 345), pre-booster CP5 and CP8 titers remained high with no increase post-booster. ClfA titers remained high after initial vaccination and increased post-booster, approaching the peak response to the initial dose. Post-booster local reactions were more frequent and of greater severity than reported after the initial vaccination, particularly for the high-dose level recipients. Post hoc analysis showed no dose-response pattern and no obvious association between diphtheria toxoid titers and local reactions after initial or booster vaccination. Immune responses after the initial vaccination persisted for the 12 months studied, with little additional response after the booster dose at 6 months. Post-booster injection site reactions were more frequent and more severe but self-limiting. CLINICALTRIALS. NCT01018641. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Hepatitis A and Hepatitis B vaccination coverage among adults with chronic liver disease

PubMed Central

Yue, Xin; Black, Carla L.; O’Halloran, Alissa; Lu, Peng-Jun; Williams, Walter W.; Nelson, Noele P.

2018-01-01

Background Infection with hepatitis A and hepatitis B virus can increase the risk of morbidity and mortality in persons with chronic liver disease (CLD). The Advisory Committee on Immunization Practices recommends hepatitis A (HepA) and hepatitis B (HepB) vaccination for persons with CLD. Methods Data from the 2014 and 2015 National Health Interview Surveys (NHIS), nationally representative, in-person interview surveys of the non-institutionalized US civilian population, were used to assess self-reported HepA (≥1 and ≥2 doses) and HepB vaccination (≥1 and ≥3 doses) coverage among adults who reported a chronic or long-term liver condition. Multivariable logistic regression was used to identify factors independently associated with HepA and HepB vaccination among adults with CLD. Results Overall, 19.4% and 11.5% of adults aged ≥18 years with CLD reported receiving ≥1 dose and ≥2 doses of HepA vaccine, respectively, compared with 14.7% and 9.1% of adults without CLD (p<0.05 comparing those with and without CLD, ≥1dose). Age, education, geographic region, and international travel were associated with receipt of ≥2 doses HepA vaccine among adults with CLD. Overall, 35.7% and 29.1% of adults with CLD reported receiving ≥1 dose and ≥3 doses of HepB vaccine, respectively, compared with 30.2% and 24.7% of adults without CLD (p<0.05 comparing those with and without CLD, ≥1 dose). Age, education, and receipt of influenza vaccination in the past 12 months were associated with receipt of ≥3 doses HepB vaccine among adults with CLD. Among adults with CLD and ≥10 provider visits, only 13.8% and 35.3% had received ≥2 doses HepA and ≥3 doses HepB vaccine, respectively. Conclusions HepA and HepB vaccination among adults with CLD is suboptimal and missed opportunities to vaccinate occurred. Providers should adhere to recommendations to vaccinate persons with CLD to increase vaccination among this population. PMID:29395521

Persistence of immunity after vaccination with a capsular group B meningococcal vaccine in 3 different toddler schedules

PubMed Central

Sadarangani, Manish; Sell, Tim; Iro, Mildred A.; Snape, Matthew D.; Voysey, Merryn; Finn, Adam; Heath, Paul T.; Bona, Gianni; Esposito, Susanna; Diez-Domingo, Javier; Prymula, Roman; Odueyungbo, Adefowope; Toneatto, Daniela; Pollard, Andrew J.

2017-01-01

BACKGROUND: One schedule for the capsular group B meningococcal vaccine 4CMenB is 2 doses that are administered 2 months apart for children aged 12–23 months, with a booster dose 12–24 months later. Our objective was to provide data on persistence of human serum bactericidal antibody (hSBA) titres in children up to 4 years of age after initial doses at 12–24 months, and immunogenicity of a booster dose at 48 months of age compared with vaccine-naive children. METHODS: Children previously immunized, as part of a randomized controlled trial, with 2 doses of 4CMenB vaccine at 12–24 months of age received a booster at 4 years of age. Vaccine-naive age-matched toddlers received 2 doses of 4CMenB. Human serum bactericidal antibody titres against reference strains H44/76, 5/99, NZ98/254 and M10713 were evaluated before and after innoculation with 4CMenB vaccine in 4-year-old children. RESULTS: Of 332 children in the study, 123 had previously received 4CMenB and 209 were vaccine-naive controls. Before the booster, the proportions of participants (previously vaccinated groups compared with controls) with hSBA titres of 1:5 or more were as follows: 9%–11% v. 1% (H44/76), 84%–100% v. 4% (5/99), 0%–18% v. 0% (NZ98/254) and 59%–60% v. 60% (M10713). After 1 dose of 4CMenB in previously immunized children, the proportions of participants achieving hSBA titres of 1:5 or more were 100% (H44/76 and 5/99), 70%–100% (NZ98/254) and 90%–100% (M10713). INTERPRETATION: We found that waning of hSBA titres by 4 years of age occurred after 2 doses of 4CMenB vaccine administered at 12–24 months, and doses at 12–24 months have a priming effect on the immune system. A booster may be necessary to maintain hSBA titres of 1:5 or more among those children with increased disease risk. Trial registration: ClinicalTrials.gov, no. NCT01717638 PMID:29038320

Predictors of hepatitis B vaccination status in healthcare workers in Belgrade, Serbia, December 2015.

PubMed

Kisic-Tepavcevic, Darija; Kanazir, Milena; Gazibara, Tatjana; Maric, Gorica; Makismovic, Natasa; Loncarevic, Goranka; Pekmezovic, Tatjana

2017-04-20

Despite the availability of a safe and effective vaccine since 1982, overall coverage of hepatitis B vaccination among healthcare workers (HCWs) has not reached a satisfactory level in many countries worldwide. The aim of this study was to estimate the prevalence of hepatitis B vaccination, and to assess the predictors of hepatitis B vaccination status among HCWs in Serbia. Of 380 randomly selected HCWs, 352 (92.6%) were included in the study. The prevalence of hepatitis B vaccination acceptance was 66.2%. The exploratory factor analyses using the vaccination-refusal scale showed that items clustered under 'threat of disease' explained the highest proportion (30.4%) of variance among those declining vaccination. The factor analyses model of the potential reasons for receiving the hepatitis B vaccine showed that 'social influence' had the highest contribution (47.5%) in explaining variance among those vaccinated. In the multivariate adjusted model the following variables were independent predictors of hepatitis B vaccination status: occupation, duration of work experience, exposure to blood in the previous year, and total hepatitis B-related knowledge score. Our results highlight the need for well-planned national policies, possibly including mandatory hepatitis B immunisation, in the Serbian healthcare environment. This article is copyright of The Authors, 2017.

Predictors of hepatitis B vaccination status in healthcare workers in Belgrade, Serbia, December 2015

PubMed Central

Kisic-Tepavcevic, Darija; Kanazir, Milena; Gazibara, Tatjana; Maric, Gorica; Makismovic, Natasa; Loncarevic, Goranka; Pekmezovic, Tatjana

2017-01-01

Despite the availability of a safe and effective vaccine since 1982, overall coverage of hepatitis B vaccination among healthcare workers (HCWs) has not reached a satisfactory level in many countries worldwide. The aim of this study was to estimate the prevalence of hepatitis B vaccination, and to assess the predictors of hepatitis B vaccination status among HCWs in Serbia. Of 380 randomly selected HCWs, 352 (92.6%) were included in the study. The prevalence of hepatitis B vaccination acceptance was 66.2%. The exploratory factor analyses using the vaccination-refusal scale showed that items clustered under ‘threat of disease’ explained the highest proportion (30.4%) of variance among those declining vaccination. The factor analyses model of the potential reasons for receiving the hepatitis B vaccine showed that ‘social influence’ had the highest contribution (47.5%) in explaining variance among those vaccinated. In the multivariate adjusted model the following variables were independent predictors of hepatitis B vaccination status: occupation, duration of work experience, exposure to blood in the previous year, and total hepatitis B-related knowledge score. Our results highlight the need for well-planned national policies, possibly including mandatory hepatitis B immunisation, in the Serbian healthcare environment. PMID:28449736

HBeAg-induced miR-106b promotes cell growth by targeting the retinoblastoma gene.

PubMed

Samal, Jasmine; Kandpal, Manish; Vivekanandan, Perumal

2017-10-30

Chronic HBV infection is a major cause of hepatocellular carcinoma (HCC). The association between hepatitis B "e" antigen (HBeAg) and HCC is well-established by epidemiological studies. Nonetheless, the biological role of HBeAg in HCC remains enigmatic. We investigate the role of HBeAg in HBV-related HCC. Our findings suggest that HBeAg enhances cell proliferation and accelerates progression from G0/G1 phase to the S phase of the cell cycle in Huh7 cells. Examination of host gene expression and miRNA expression profiles reveals a total of 21 host genes and 12 host miRNAs that were differentially regulated in cells expressing HBeAg. Importantly, HBeAg induced the expression of miR-106b, an oncogenic miRNA. Interestingly, HBeAg-expression results in a significant reduction in the expression of retinoblastoma (Rb) gene, an experimentally validated target of miR-106b. Inhibition of miR-106b significantly increased the expression of the Rb gene, resulting in reduced cell proliferation and slowing of cell cycle progression from the G0/G1 phase to S phase. These observations suggest that the up-regulation of miR-106b by HBeAg contributes to the pathogenesis of HBV-related HCC by down-regulating the Rb gene. Our results highlight a role for HBeAg in HCC and provide a novel perspective on the molecular mechanisms underlying HBV-related HCC.

Safety and Immunogenicity of a Candidate Parvovirus B19 Vaccine

PubMed Central

Bernstein, David I; El Sahly, Hana M; Keitel, Wendy A; Wolff, Mark; Simone, Gina; Segawa, Claire; Wong, Susan; Shelly, Daniel; Young, Neal S; Dempsey, Walla

2011-01-01

Parvovirus B19 is an important human pathogen causing erythema infectiosum, transient aplastic crisis in individuals with underlying hemolytic disorders and hydrops fetalis. We therefore evaluated a parvovirus B19 virus like particle (VLP) vaccine. The safety and immunogenicity of a 25 μg dose of parvovirus B19 recombinant capsid; 2.5 and 25 μg doses of the recombinant capsid given with MF59; and saline placebo were assessed in healthy adults. Because of 3 unexplained cutaneous events the study was halted after enrollment of 43 subjects and before any subject received their third scheduled dose. The rashes developed 5-9 days after the first or second injection and were seen in one placebo recipient (without an injection site lesion) and two vaccine recipients (with injection site reactions). No clear cause was established. Other safety evaluations revealed mostly injection site reactions that were mild to moderate with an increase in pain in subjects receiving vaccine and MF59. After dose 2 the majority of vaccine recipients developed ELISA and neutralizing antibody to parvovirus B19. Given the possible severe consequences of parvovirus B19 infection, further development of a safe and effective vaccine continues to be important. PMID:21807052

Safety and immunogenicity of a candidate parvovirus B19 vaccine.

PubMed

Bernstein, David I; El Sahly, Hana M; Keitel, Wendy A; Wolff, Mark; Simone, Gina; Segawa, Claire; Wong, Susan; Shelly, Daniel; Young, Neal S; Dempsey, Walla

2011-10-06

Parvovirus B19 is an important human pathogen causing erythema infectiosum, transient aplastic crisis in individuals with underlying hemolytic disorders and hydropsfetalis. We therefore evaluated a parvovirus B19 virus like particle (VLP) vaccine. The safety and immunogenicity of a 25 μg dose of parvovirus B19 recombinant capsid; 2.5 and 25 μg doses of the recombinant capsid given with MF59; and saline placebo were assessed in healthy adults. Because of 3 unexplained cutaneous events the study was halted after enrollment of 43 subjects and before any subject received their third scheduled dose. The rashes developed 5-9 days after the first or second injection and were seen in one placebo recipient (without an injection site lesion) and two vaccine recipients (with injection site reactions). No clear cause was established. Other safety evaluations revealed mostly injection site reactions that were mild to moderate with an increase in pain in subjects receiving vaccine and MF59. After dose 2 the majority of vaccine recipients developed ELISA and neutralizing antibody to parvovirus B19. Given the possible severe consequences of parvovirus B19 infection, further development of a safe and effective vaccine continues to be important. Copyright © 2011 Elsevier Ltd. All rights reserved.

Media and public reactions toward vaccination during the 'hepatitis B vaccine crisis' in China.

PubMed

Chen, Bin; Zhang, Jueman Mandy; Jiang, Zhenggang; Shao, Jian; Jiang, Tao; Wang, Zhengting; Liu, Kui; Tang, Siliang; Gu, Hua; Jiang, Jianmin

2015-04-08

Public disputations affected vaccine confidence and vaccine rates particularly when adverse events occur. The vigorous development of Internet in China provides an opportunity to observe public reaction and sentiment toward vaccination when Kangtai Hepatitis B vaccine crisis happened and evolved to a widespread debate on the internet from December 12, 2013 to January 3, 2014. This study conducted Internet surveillance by examining three daily indicators including the daily number of relevant online news article, Sina Weibo posts and Baidu search index during the crisis. We also analyzed the sentiments of relevant original microblog posts collected from Sina Weibo platform in the crisis. A total of 17 infant deaths were reported to associated with Hepatitis B vaccination. Three major waves of high media and public attention were detected. The daily indicators reached their peaks in the second wave after the relevant vaccine was suspended by the authority (from December 20 to December 29, 2013) with 23,200 daily online news reports, 34,018 Sina Weibo posts and 17,832 Baidu search indices. There were significant correlations between the daily amount of online news, Weibo posts, and Baidu searches (p<.001). The contents analysis suggested 1343 out of 1608 (83.5%) original Weibo posts expressed negative sentiment with almost 90% in the second wave. This study found the Kangtai vaccine crisis raised great public attention and negative sentiment toward vaccinations on the internet in China. Policy change such as suspension of the suspected vaccine might trigger even greater reaction and more negative sentiment. The government should provide ways to address emerging public concerns after policy change to avoid misinformation and misunderstanding during such a vaccine crisis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Immunogenicity and safety of concomitant administration of a combined hepatitis A/B vaccine and a quadrivalent meningococcal conjugate vaccine in healthy adults.

PubMed

Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil C; Meyer, Seetha; Forleo-Neto, Eduardo; Dagnew, Alemnew F; Arora, Ashwani Kumar

2015-01-01

This phase 3b randomized, open-label study evaluated the immunogenicity and safety of coadministration of a hepatitis A and/or B vaccine with a quadrivalent oligosaccharide meningococcal CRM197 -conjugate vaccine (MenACWY-CRM), in the context of an accelerated hepatitis A and/or B immunization schedule. A total of 252 healthy adult subjects were randomized to three groups to receive hepatitis A/B only (HepA/B), hepatitis A/B coadministered with MenACWY-CRM (HepA/B+MenACWY-CRM), or MenACWY-CRM only (MenACWY-CRM). Hepatitis A and/or B vaccination was administered in the form of a single booster dose or a primary three-dose series, depending on the hepatitis A and/or B vaccination history of subjects. Antibody responses to hepatitis A/B vaccination were assessed 1 month following the last hepatitis A and/or B dose. Serum bactericidal activity with human complement (hSBA) against meningococcal serogroups A, C, W-135, and Y was assessed 1 month post-MenACWY-CRM vaccination. Safety was monitored throughout the study. At 1 month following the final hepatitis A and/or B vaccination, concomitant administration of hepatitis A/B and MenACWY-CRM was non-inferior to administration of hepatitis A/B alone in terms of geometric mean concentrations of antibodies against the hepatitis A and B antigens. One month post-MenACWY-CRM vaccination, the percentages of subjects achieving hSBA titers ≥8 for serogroups A, C, W-135, and Y in the HepA/B+MenACWY-CRM group (76, 87, 99, and 94%, respectively) were comparable to those in the MenACWY-CRM group (67, 82, 96, and 88%, respectively). The percentages of subjects reporting adverse events (AEs) were similar across study groups and a majority of the reported AEs were mild to moderate in nature. There were no study vaccine-related serious AEs. MenACWY-CRM can be administered concomitantly with a hepatitis A and/or B vaccine in the context of an accelerated hepatitis A and/or B immunization schedule without increasing safety concerns

[Vaccines against hepatitis A and B in Chile].

PubMed

Valenzuela, M Teresa

2009-06-01

The mode of transmission and epidemiological approach for hepatitis A and B are different. However, both are preventable with vaccines whose efficacy and long lasting protection has been demonstrated. This review describes the secular tendency of both infections in Chile, their risk factors that have contributed to their persistence in the country and the interventions that have been carried out to reduce the disease burden. Although the vaccine for hepatitis B was incorporated to the immunization program in 2005, the vaccine for hepatitis A persists in the list of interventions that must be assumed with priority by the Ministry of Health. If Chilean health authorities pretend to reach the enteric disease indicators of developed countries, they must accelerate the epidemiological transition towards the elimination of hepatitis A.

RTS,S/AS01E Malaria Vaccine Induces Memory and Polyfunctional T Cell Responses in a Pediatric African Phase III Trial.

PubMed

Moncunill, Gemma; De Rosa, Stephen C; Ayestaran, Aintzane; Nhabomba, Augusto J; Mpina, Maximillian; Cohen, Kristen W; Jairoce, Chenjerai; Rutishauser, Tobias; Campo, Joseph J; Harezlak, Jaroslaw; Sanz, Héctor; Díez-Padrisa, Núria; Williams, Nana Aba; Morris, Daryl; Aponte, John J; Valim, Clarissa; Daubenberger, Claudia; Dobaño, Carlota; McElrath, M Juliana

2017-01-01

Comprehensive assessment of cellular responses to the RTS,S/AS01E vaccine is needed to understand potential correlates and ultimately mechanisms of protection against malaria disease. Cellular responses recognizing the RTS,S/AS01E-containing circumsporozoite protein (CSP) and Hepatitis B surface antigen (HBsAg) were assessed before and 1 month after primary vaccination by intracellular cytokine staining and 16-color flow cytometry in 105 RTS,S/AS01-vaccinated and 74 rabies-vaccinated participants (controls) in a pediatric phase III trial in Africa. RTS,S/AS01E-vaccinated children had significantly higher frequencies of CSP- and HBsAg-specific CD4 + T cells producing IL-2, TNF-α, and CD40L and HBsAg-specific CD4 + T producing IFN-γ and IL-17 than baseline and the control group. Vaccine-induced responses were identified in both central and effector memory (EM) compartments. EM CD4 + T cells expressing IL-4 and IL-21 were detected recognizing both vaccine antigens. Consistently higher response rates to both antigens in RTS,S/AS01E-vaccinated than comparator-vaccinated children were observed. RTS,S/AS01E induced polyfunctional CSP- and HBsAg-specific CD4 + T cells, with a greater degree of polyfunctionality in HBsAg responses. In conclusion, RTS,S/AS01E vaccine induces T cells of higher functional heterogeneity and polyfunctionality than previously characterized. Responses detected in memory CD4 + T cell compartments may provide correlates of RTS,S/AS01-induced immunity and duration of protection in future correlates of immunity studies.

Study of energy transfer between riboflavin (vitamin B2) and AgNPs

NASA Astrophysics Data System (ADS)

Mokashi, Vidya V.; Walekar, Laxman S.; Anbhule, Prashant V.; Lee, Sang Hak; Patil, Shivajirao R.; Kolekar, Govind B.

2014-03-01

Here, we report the studies on the interaction and formation of nanobiocomplex between silver nanoparticle (AgNPs) and vitamin B2, i.e., riboflavin (RF). The binding study of AgNP to RF was studied by fluorescence, UV-Vis, and TEM techniques. AgNPs were prepared by reducing AgNO3 with trisodium citrate. Prepared nanoparticles size obtained at 20 nm having surface Plasmon resonance band at 426 nm. The absorbance band of RF at 264, 374, and 444 nm changes significantly in the presence of AgNPs suggests that there is change in the chemical environment surrounding AgNPs. A fluorescence spectral change for a solution of RF upon the addition of AgNPs and rapid quenching is suggestive of a rapid adsorption of RF on AgNPs.

[Immunization strategy of hepatitis B vaccine among adults in China: evidence based-medicine and consideration].

PubMed

Xu, A Q; Zhang, L

2016-06-01

With the effective control of hepatitis B infection among children, the adults especial the young ones become the main population for new hepatitis B virus infection. Now the adults receive hepatitis B vaccination voluntarily and at their own expense in China and the coverage is low. The high immunogenicity of hepatitis B vaccine has been proven among healthy adults. Although the safety of hepatitis B vaccination has been documented among high-risk population such as HIV-infected people, injecting drug users and patients with chronic hepatitis disease, their antibody seroconversion rate after hepatitis B vaccination is lower than the healthy adults. Hepatitis B vaccination is recommended to population at high risk officially in many countries and some effects have been achieved. It is urgent to improve the strategy of hepatitis B vaccination among adults to fasten the control of hepatitis B in China, along with the researches about the long-term efficacy of hepatitis B vaccine among adults, the immunogenicity of hepatitis B vaccination among high-risk adults and the economical evaluation about different adult immunization strategy of hepatitis B.

Hepatitis B vaccination for reducing morbidity and mortality in persons with HIV infection

PubMed Central

Okwen, Mbah P; Reid, Savanna; Njei, Basile; Mbuagbaw, Lawrence

2016-01-01

Background Hepatitis B vaccine has been recommended for use in people living with HIV (PLHIV) mostly because of the similarities in routes of infection and their prevalence in the same geographic areas. PLHIV may not develop sero-protection after receiving standard hepatitis B vaccine due to their compromised immune status. Objectives To evaluate the efficacy of hepatitis B virus vaccine in PLHIV compared to placebo or no vaccine. Search methods We searched 6 English language databases in July 2012, and updated the search in June 2013 and August 2014. We searched the grey literature, conference proceedings, specialised web sites, and contacted experts in the field. Selection criteria Randomised controlled trials of hepatitis B vaccine compared to placebo or no vaccine, evaluating relevant outcomes of efficacy and safety. Data collection and analysis Two review authors independently sought and extracted data on study design, participants, hepatitis B infection, hepatitis B related morbidity and mortality, anti-HBs immunogenicity and adverse effects related to vaccines from published articles or through correspondence with authors. Data were analysed qualitatively. Main results One double-blind randomised controlled trial with 26 participants who were on antiretroviral therapy (ART), comparing hepatitis B vaccine to placebo conducted in Spain met our eligibility criteria and was included in this review. The study ran for three years and participants were followed up on a monthly basis. The study reported adequate humoral response to vaccine at 12 months and no local or systematic side effects in both intervention and control groups. This humoral response was lost when the participants stopped taking ART. The sample size of the study was small and the study was conducted in a high income setting unlike the areas of highest burden of hepatitis B and HIV co-infections. Authors’ conclusions The evidence from this study is insufficient to support any recommendations

Tuberculosis vaccine candidate: Characterization of H4-IC31 formulation and H4 antigen conformation.

PubMed

Deshmukh, Sasmit S; Magcalas, Federico Webster; Kalbfleisch, Kristen N; Carpick, Bruce W; Kirkitadze, Marina D

2018-08-05

Tuberculosis (TB) is one of the leading causes of death worldwide, making the development of effective TB vaccines a global priority. A TB vaccine consisting of a recombinant fusion protein, H4, combined with a novel synthetic cationic adjuvant, IC31 ® , is currently being developed. The H4 fusion protein consists of two immunogenic mycobacterial antigens, Ag85 B and TB10.4, and the IC31 ® adjuvant is a mixture of KLK, a leucine-rich peptide (KLKL5KLK), and the oligodeoxynucleotide ODN1a, a TLR9 ligand. However, efficient and robust methods for assessing these formulated components are lacking. Here, we developed and optimized phase analysis light scattering (PALS), electrical sensing zone (ESZ), and Raman, FTIR, and CD spectroscopy methods to characterize the H4-IC31 vaccine formulation. PALS-measured conductivity and zeta potential values could differentiate between the similarly sized particles of IC31 ® adjuvant and the H4-IC31 vaccine candidate and could thereby serve as a control during vaccine formulation. In addition, zeta potential is indicative of the adjuvant to antigen ratio which is the key in the immunomodulatory response of the vaccine. ESZ was used as an orthogonal method to measure IC31 ® and H4-IC31 particle sizes. Raman, FTIR, and CD spectroscopy revealed structural changes in H4 protein and IC31 ® adjuvant, inducing an increase in both the β-sheet and random coil content as a result of adsorption. Furthermore, nanoDSF showed changes in the tertiary structure of H4 protein as a result of adjuvantation to IC31 ® . Our findings demonstrate the applicability of biophysical methods to characterize vaccine components in the final H4-IC31 drug product without the requirement for desorption. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Hepatitis B maternal screening, infant vaccination, and infant prophylaxis practices in North Carolina.

PubMed

Pierce, R L; Smith, S; Rowe-West, B; Sterritt, B

1999-06-01

To determine if the Advisory Committee on Immunization Practices hepatitis B screening, vaccination, and prophylaxis recommendations were being followed in North Carolina, and to establish a baseline hepatitis B seroprevalence rate. A survey of mother and infant birthing facility medical records. Four birthing facilities selected from each of the 7 districts in North Carolina (a total of 28 facilities). A probability proportional to size survey design was used to select 4763 mother-infant record pairs. All records came from the 1996 birth cohort. Maternal hepatitis B screening status, infant vaccination status, infants prophylaxis status, hepatitis B seroprevalence rate, demographic and clinical predictors for maternal infection, failure to receive prenatal care or for whom status was unknown, failure to screen, and failure to vaccinate. Ninety-two percent of pregnant women were screened for hepatitis B surface antigen. Eighty-six percent of infants received dose 1 of the hepatitis B vaccine. Four of the 9 infants with mothers who were hepatitis B surface antigen-positive did not receive both vaccine and hepatitis B immune globulin. The hepatitis B seroprevalence rate was 0.2%. Mothers who were not screened for infection were 3.4 times more likely to have infants who were not vaccinated. White mothers were twice as likely not to have their child vaccinated as mothers of other races. Not all infants with hepatitis B-infected mothers were receiving vaccine and hepatitis B immune globulin as recommended. Seroprevalence of hepatitis B infection may be lower in North Carolina than in other states. Hepatitis B laboratory test results should be included in every mother's medical record.

Economic evaluation of meningococcal serogroup B childhood vaccination in Ontario, Canada.

PubMed

Tu, Hong Anh T; Deeks, Shelley L; Morris, Shaun K; Strifler, Lisa; Crowcroft, Natasha; Jamieson, Frances B; Kwong, Jeffrey C; Coyte, Peter C; Krahn, Murray; Sander, Beate

2014-09-22

Invasive Neisseria meningitidis serogroup B (MenB) disease is a low incidence but severe infection (mean annual incidence 0.19/100,000/year, case fatality 11%, major long-term sequelae 10%) in Ontario, Canada. This study assesses the cost-effectiveness of a novel MenB vaccine from the Ontario healthcare payer perspective. A Markov cohort model of invasive MenB disease based on high quality local data and data from the literature was developed. A 4-dose vaccination schedule, 97% coverage, 90% effectiveness, 66% strain coverage, 10-year duration of protection, and vaccine cost of C$75/dose were assumed. A hypothetical Ontario birth cohort (n=150,000) was simulated to estimate expected lifetime health outcomes, quality-adjusted life years (QALYs), and costs, discounted at 5%. A MenB infant vaccination program is expected to prevent 4.6 invasive MenB disease cases over the lifetime of an Ontario birth cohort, equivalent to 10 QALYs gained. The estimated program cost of C$46.6 million per cohort (including C$318,383 for treatment of vaccine-associated adverse events) were not offset by healthcare cost savings of C$150,522 from preventing MenB cases, resulting in an incremental cost of C$4.76 million per QALY gained. Sensitivity analyses showed the findings to be robust. An infant MenB vaccination program significantly exceeds commonly used cost-effectiveness thresholds and thus is unlikely to be considered economically attractive in Ontario and comparable jurisdictions. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Advances in hepatitis immunization (A, B, E): public health policy and novel vaccine delivery.

PubMed

Hendrickx, Greet; Vorsters, Alex; Van Damme, Pierre

2012-10-01

This review offers an update on hepatitis A, B and E vaccines based on relevant literature published in 2011-2012. Hepatitis A and B vaccines have been commercially available for years; however, the development of the hepatitis E vaccine is still facing some challenges. Current scientific evidence shows that both hepatitis A and B vaccines confer long-term protection. These data supported the updated recommendations from the WHO on hepatitis A and B vaccines and the respective booster policy. In addition, a single-dose hepatitis A vaccination programme may be an option for some intermediate endemic countries, as far as the epidemiological situation is further monitored. Recent data illustrate the co-administration of hepatitis A with infant vaccines, as well as the interchangeability with other hepatitis A vaccines. Two genetically engineered hepatitis E vaccines are currently in development, showing more than 95% protective efficacy. Follow-up of vaccinated individuals confirms the long-term protection offered by the hepatitis A as well as hepatitis B vaccines. Data confirm the safety and immunogenicity profile of both vaccines, also when used in patient groups. The first data on the hepatitis E vaccine look promising, but questions on cross-protection, long-term efficacy and safety and immunogenicity in pregnant women and children less than 2 years remain unanswered.

Hepatitis A and B superimposed on chronic liver disease: vaccine-preventable diseases.

PubMed

Keeffe, Emmet B

2006-01-01

A number of studies have demonstrated that the acquisition of hepatitis A or hepatitis B in patients with chronic liver disease is associated with high rates of morbidity and mortality. Superimposition of acute hepatitis A in patients with chronic hepatitis C has been associated with a particularly high mortality rate, and chronic hepatitis B virus coinfection with hepatitis C virus is associated with an accelerated progression of chronic liver disease to cirrhosis, decompensated liver disease and hepatocellular carcinoma. With the availability of vaccines against hepatitis B and hepatitis A since 1981 and 1995, respectively, these are vaccine-preventable diseases. Studies have confirmed that hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild to moderate chronic liver disease. However, hepatitis A and B vaccination is less effective in patients with advanced liver disease and after liver transplantation. These observations have led to the recommendation that patients undergo hepatitis A and B vaccination early in the natural history of their chronic liver disease. Vaccination rates are low in clinical practice, and public health and educational programs are needed to overcome barriers to facilitate timely implementation of these recommendations.

Hepatitis A and B Superimposed on Chronic Liver Disease: Vaccine-Preventable Diseases

PubMed Central

Keeffe, Emmet B

2006-01-01

A number of studies have demonstrated that the acquisition of hepatitis A or hepatitis B in patients with chronic liver disease is associated with high rates of morbidity and mortality. Superimposition of acute hepatitis A in patients with chronic hepatitis C has been associated with a particularly high mortality rate, and chronic hepatitis B virus coinfection with hepatitis C virus is associated with an accelerated progression of chronic liver disease to cirrhosis, decompensated liver disease and hepatocellular carcinoma. With the availability of vaccines against hepatitis B and hepatitis A since 1981 and 1995, respectively, these are vaccine-preventable diseases. Studies have confirmed that hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild to moderate chronic liver disease. However, hepatitis A and B vaccination is less effective in patients with advanced liver disease and after liver transplantation. These observations have led to the recommendation that patients undergo hepatitis A and B vaccination early in the natural history of their chronic liver disease. Vaccination rates are low in clinical practice, and public health and educational programs are needed to overcome barriers to facilitate timely implementation of these recommendations. PMID:18528476

Characterization of a Novel Fusion Protein from IpaB and IpaD of Shigella spp. and Its Potential as a Pan-Shigella Vaccine

PubMed Central

Martinez-Becerra, Francisco J.; Chen, Xiaotong; Dickenson, Nicholas E.; Choudhari, Shyamal P.; Harrison, Kelly; Clements, John D.; Picking, William D.; Van De Verg, Lillian L.; Walker, Richard I.

2013-01-01

Shigellosis is an important disease in the developing world, where about 90 million people become infected with Shigella spp. each year. We previously demonstrated that the type three secretion apparatus (T3SA) proteins IpaB and IpaD are protective antigens in the mouse lethal pulmonary model. In order to simplify vaccine formulation and process development, we have evaluated a vaccine design that incorporates both of these previously tested Shigella antigens into a single polypeptide chain. To determine if this fusion protein (DB fusion) retains the antigenic and protective capacities of IpaB and IpaD, we immunized mice with the DB fusion and compared the immune response to that elicited by the IpaB/IpaD combination vaccine. Purification of the DB fusion required coexpression with IpgC, the IpaB chaperone, and after purification it maintained the highly α-helical characteristics of IpaB and IpaD. The DB fusion also induced comparable immune responses and retained the ability to protect mice against Shigella flexneri and S. sonnei in the lethal pulmonary challenge. It also offered limited protection against S. dysenteriae challenge. Our results show the feasibility of generating a protective Shigella vaccine comprised of the DB fusion. PMID:24060976

Combined hepatitis A and B vaccines: a review of their immunogenicity and tolerability.

PubMed

Murdoch, David L; Goa, Karen; Figgitt, David P

2003-01-01

Three combined hepatitis A and B vaccine preparations are commercially available in various countries: a two-dose paediatric formulation (Ambirix) [administered at months 0 and 6-12]; and a three-dose adult (Twinrix Adult) or paediatric (Twinrix Paediatric) formulation (administered at months 0, 1 and 6). The adult vaccine provides consistent, marked immunogenicity which is at least similar to that of its constituent vaccines used together and with a tolerability profile that is possibly improved. An accelerated, day-0, -7 and -21 regimen has also shown immunogenicity similar to that of the monovalent vaccines given concurrently, and now has an emerging role in adults likely to travel to hepatitis A virus (HAV) and/or hepatitis B virus (HBV) endemic regions within 1 month. The adult vaccine appears effective and generally well tolerated when given concurrently with monovalent typhoid vaccine (Typherix). Immunogenicity of the two-dose paediatric vaccine is high and appears to be similar whether administered as a month-0, -6 or month-0, -12 schedule and when compared to that of the three-dose paediatric vaccine (months 0, 1, 6), both of which provide a similar degree of protection to the adult vaccine. Although both preparations also provide high end-of-schedule seroprotection against hepatitis B surface antigen, protection between the first and second doses of the two-dose regimen appears lower than with the three-dose schedule. Therefore, the three-dose paediatric vaccine is a practical option in individuals at risk of immediate exposure to HBV, while the two-dose regimen may have an important function in immunisation programmes in regions where such risk is low. Combined hepatitis A and B vaccines are generally well tolerated. The most frequently reported adverse events in clinical trials were injection-site pain and redness, and general fatigue and headache; most events were mild and transient. Pharmacoeconomic models suggest the combined vaccine is cost

Long-term persistence in protection and response to a hepatitis B vaccine booster among adolescents immunized in infancy in the western region of China.

PubMed

Wang, Zhen-Zi; Gao, Yu-Hua; Lu, Wei; Jin, Cun-Duo; Zeng, Ying; Yan, Ling; Ding, Feng; Li, Tong; Liu, Xue-En; Zhuang, Hui

2017-04-03

To evaluate the persistence of protection from hepatitis B (HB) vaccination among adolescents immunized with a primary series of HB vaccine as infants, and the immune response to booster doses. Healthy adolescents aged 15-17 y vaccinated with HB vaccine only at birth were enrolled. Baseline serum hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected by Enzyme-Linked Immunosorbent Assay (ELISA) and anti-HBs level was measured using Chemiluminescent Microparticle Immunoassay (CMIA). The rate of HBV infection was calculated. The seroprotection rate of anti-HBs (≥ 10 mIU/ml) and GMC level were used to evaluate the persistence of immunity from HB vaccination. Those with anti-HBs < 10 mIU/ml were immunized with booster doses of HB vaccine and the anamnestic response was assessed. Of 180 adolescents who received a primary series of HB vaccinations as infants, 3 (1.7%) had HBV infection and 74 (41.1%) had anti-HBs ≥ 10 mIU/ml with a GMC of 145.11 mIU/ml. The remaining 103 (57.2%) with anti-HBs < 10 mIU/ml received a booster dose of 20 μg HB vaccine and achieved the seroprotection rate of 84% (84/100) and a GMC of 875.19 mIU/ml at one month post-booster. An additional dose of 60 μg HB vaccine was administered to the 16 adolescents with anti-HBs < 10 mIU/ml after the first booster. All of them obtained anti-HBs seroprotection with a GMC of 271.02 mIU/ml at 1.5 months after an additional dose. Vaccine-induced immunity persisted for up to 15-17 y in 89.3% (158/177) of participants after a primary HB vaccination in infancy. Administering a booster dose of 20μg HB vaccine elicited an anamnestic immune responses in the majority of individuals with baseline anti-HBs <10 mIU/ml.

Long-term persistence in protection and response to a hepatitis B vaccine booster among adolescents immunized in infancy in the western region of China

PubMed Central

Wang, Zhen-Zi; Gao, Yu-Hua; Lu, Wei; Jin, Cun-Duo; Zeng, Ying; Yan, Ling; Ding, Feng; Li, Tong; Liu, Xue-En; Zhuang, Hui

2017-01-01

ABSTRACT Objectives: To evaluate the persistence of protection from hepatitis B (HB) vaccination among adolescents immunized with a primary series of HB vaccine as infants, and the immune response to booster doses. Methods: Healthy adolescents aged 15–17 y vaccinated with HB vaccine only at birth were enrolled. Baseline serum hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected by Enzyme-Linked Immunosorbent Assay (ELISA) and anti-HBs level was measured using Chemiluminescent Microparticle Immunoassay (CMIA). The rate of HBV infection was calculated. The seroprotection rate of anti-HBs (≥ 10 mIU/ml) and GMC level were used to evaluate the persistence of immunity from HB vaccination. Those with anti-HBs < 10 mIU/ml were immunized with booster doses of HB vaccine and the anamnestic response was assessed. Results: Of 180 adolescents who received a primary series of HB vaccinations as infants, 3 (1.7%) had HBV infection and 74 (41.1%) had anti-HBs ≥ 10 mIU/ml with a GMC of 145.11 mIU/ml. The remaining 103 (57.2%) with anti-HBs < 10 mIU/ml received a booster dose of 20 μg HB vaccine and achieved the seroprotection rate of 84% (84/100) and a GMC of 875.19 mIU/ml at one month post-booster. An additional dose of 60 μg HB vaccine was administered to the 16 adolescents with anti-HBs < 10 mIU/ml after the first booster. All of them obtained anti-HBs seroprotection with a GMC of 271.02 mIU/ml at 1.5 months after an additional dose. Conclusions: Vaccine-induced immunity persisted for up to 15–17 y in 89.3% (158/177) of participants after a primary HB vaccination in infancy. Administering a booster dose of 20μg HB vaccine elicited an anamnestic immune responses in the majority of individuals with baseline anti-HBs <10 mIU/ml. PMID:27874311

Long-Term Effectiveness of Accelerated Hepatitis B Vaccination Schedule in Drug Users

PubMed Central

Shah, Dimpy P.; Grimes, Carolyn Z.; Nguyen, Anh T.; Lai, Dejian

2015-01-01

Objectives. We demonstrated the effectiveness of an accelerated hepatitis B vaccination schedule in drug users. Methods. We compared the long-term effectiveness of accelerated (0–1–2 months) and standard (0–1–6 months) hepatitis B vaccination schedules in preventing hepatitis B virus (HBV) infections and anti-hepatitis B (anti-HBs) antibody loss during 2-year follow-up in 707 drug users (HIV and HBV negative at enrollment and completed 3 vaccine doses) from February 2004 to October 2009. Results. Drug users in the accelerated schedule group had significantly lower HBV infection rates, but had a similar rate of anti-HBs antibody loss compared with the standard schedule group over 2 years of follow-up. No chronic HBV infections were observed. Hepatitis C positivity at enrollment and age younger than 40 years were independent risk factors for HBV infection and antibody loss, respectively. Conclusions. An accelerated vaccination schedule was more preferable than a standard vaccination schedule in preventing HBV infections in drug users. To overcome the disadvantages of a standard vaccination schedule, an accelerated vaccination schedule should be considered in drug users with low adherence. Our study should be repeated in different cohorts to validate our findings and establish the role of an accelerated schedule in hepatitis B vaccination guidelines for drug users. PMID:25880946

Hepatitis A and hepatitis B vaccination coverage among adults with chronic liver disease.

PubMed

Yue, Xin; Black, Carla L; O'Halloran, Alissa; Lu, Peng-Jun; Williams, Walter W; Nelson, Noele P