Lack of Response to Recombinant Hepatitis B Vaccine in Nonresponders to the Plasma Vaccine

Weissman, Joy Y.; Tsuchiyose, Mark M.; Tong, Myron J.; Co, Ruth L.; Chin, Kenneth P.; Ettenger, Robert B.

doi:10.1001/jama.1988.03410120080031

Cited by 62 publications

(34 citation statements)

References 26 publications

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“…Similarly, in our recent phase I MAP trial, individuals of high responder genotypes who were heterozygous for DR7 also failed to develop the expected high levels of Ab and T cell responses (7). Poor humoral responses following immunization with hepatitis and measles vaccines have also been noted in DR7 heterozygotes (33,34). However, one of the three DR7-positive polyoxime vaccinees, volunteer no.…”

Section: Discussionmentioning

confidence: 74%

A Totally Synthetic Polyoxime Malaria Vaccine Containing Plasmodium falciparum B Cell and Universal T Cell Epitopes Elicits Immune Responses in Volunteers of Diverse HLA Types

Nardin

Calvo‐Calle

Oliveira

et al. 2001

The Journal of Immunology

145

126

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This open-labeled phase I study provides the first demonstration of the immunogenicity of a precisely defined synthetic polyoxime malaria vaccine in volunteers of diverse HLA types. The polyoxime, designated (T1BT*)4-P3C, was constructed by chemoselective ligation, via oxime bonds, of a tetrabranched core with a peptide module containing B cell epitopes and a universal T cell epitope of the Plasmodium falciparum circumsporozoite protein. The triepitope polyoxime malaria vaccine was immunogenic in the absence of any exogenous adjuvant, using instead a core modified with the lipopeptide P3C as an endogenous adjuvant. This totally synthetic vaccine formulation can be characterized by mass spectroscopy, thus enabling the reproducible production of precisely defined vaccines for human use. The majority of the polyoxime-immunized volunteers (7/10) developed high levels of anti-repeat Abs that reacted with the native circumsporozoite on P. falciparum sporozoites. In addition, these seven volunteers all developed T cells specific for the universal epitope, termed T*, which was originally defined using CD4+ T cells from protected volunteers immunized with irradiated P. falciparum sporozoites. The excellent correlation of T*-specific cellular responses with high anti-repeat Ab titers suggests that the T* epitope functioned as a universal Th cell epitope, as predicted by previous peptide/HLA binding assays and by immunogenicity studies in mice of diverse H-2 haplotypes. The current phase I trial suggests that polyoximes may prove useful for the development of highly immunogenic, multicomponent synthetic vaccines for malaria, as well as for other pathogens.

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Section: Discussionmentioning

confidence: 74%

A Totally Synthetic Polyoxime Malaria Vaccine Containing Plasmodium falciparum B Cell and Universal T Cell Epitopes Elicits Immune Responses in Volunteers of Diverse HLA Types

Nardin

Calvo‐Calle

Oliveira

et al. 2001

The Journal of Immunology

145

126

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“…by applying double vaccination dose [31] , using intradermal boosters [32][33][34] , or adding adjuvants such as monophosphoryl lipid A (MPLA) or influenza vaccine [35,36] . Although these measures were more effective than the yeast derived hepatitis B vaccine alone, not all nonresponders showed seroconversion.…”

Section: Weihrauch Mr Et Al T-cell Response In Hepatitis Bs Non-respmentioning

confidence: 99%

T cell responses to hepatitis B surface antigen are detectable in non-vaccinated individuals

Weihrauch¹,

Bergwelt‐Baildon²,

Kandic³

et al. 2008

WJG

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CONCLUSION:Our data suggest that there is no general immune deficiency in non-/low-responders. Thus, we hypothesize that the induction of anti-HBsAg responses by vaccination is significantly dependent on the pre-existing T cell repertoire against the specific antigen rather than the presence of a general T cell defect. INTRODUCTIONWorldwide, hepatitis B virus (HBV) infections are a growing problem with a high prevalence of over 8% hepatitis B surface antigen (HBsAg) positive individuals in Africa, South America, parts of Eastern Europe, South Asia, and Canada [1] . It is estimated that approximately 350 million people are chronic carriers of HBV with 1-1.5 million dying from liver cirrhosis and primary liver cancer [2] . Nowadays, protective repeated vaccinations with recombinant HBsAg are not only recommended to all health care workers and travellers, but have recently been included in the childhood and adolescence immunization schedule. Hepatitis B vaccinations prevent HBV infections as well as its complications in most of the vaccines [3,4] . However, 5% to 10% fail to produce protective anti-HBsAg titers after three vaccinations irrespective of the source of the antigen, which is a problem not only for health care workers, and represents a major medical as well as economic challenge [5][6][7] . Low-(HBsAg titer 10-99 kU/L) or Abstract AIM: To evaluate, whether humoral hepatitis-B-vaccine non-responders also fail to mount a T cell response and to compare these results to normal vaccines. RAPID COMMUNICATION T cell responses to hepatitis B surface antigen are detectable in non-vaccinated individuals

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“…Current guidelines 1,2 recommend additional intramuscular doses, although response rates are generally less than 50%. [8][9][10] In contrast, response rates of approximately 90% have been reported with intradermal hepatitis B vaccine using either recombinant 11,12 or plasma-derived vaccine. 13 This study was undertaken to further assess the humoral immune responses, safety, and tolerability of intradermal recombinant hepatitis B vaccination in HCWs nonresponsive to repeated previous intramuscular vaccination.…”

mentioning

confidence: 99%

Intradermal Recombinant Hepatitis B Vaccine for Healthcare Workers Who Fail to Respond to Intramuscular Vaccine

Playford

Hogan

Bansal

et al. 2002

Infect. Control Hosp. Epidemiol.

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Objective:To study the humoral immune responses, safety, and tolerability of intradermal recombinant hepatitis B vaccination in healthcare workers (HCWs) nonresponsive to previous repeated intramuscular vaccination.Design:An open, prospective, before–after trial.Setting:A tertiary referral hospital and surrounding district health service in Queensland, Australia.Participants:Hospital and community HCWs nonresponsive to previous intramuscular hepatitis B vaccination.Methods:Intradermal recombinant hepatitis B vaccine was administered every second week for a maximum of 4 doses. Hepatitis B surface antibody (anti-HBs) responses were assessed 2 weeks after each dose.Results:Protective anti-HBs levels developed in 17 (94%) of 18 study subjects. Three doses resulted in seroconversion of all responding subjects and the highest geometric mean antibody concentration. The vaccine was well tolerated.Conclusion:More than 90% of previously nonresponsive HCWs responded to intradermal recombinant hepatitis B vaccine with protective anti-HBs levels.

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Lack of Response to Recombinant Hepatitis B Vaccine in Nonresponders to the Plasma Vaccine

Cited by 62 publications

References 26 publications

A Totally Synthetic Polyoxime Malaria Vaccine Containing Plasmodium falciparum B Cell and Universal T Cell Epitopes Elicits Immune Responses in Volunteers of Diverse HLA Types

A Totally Synthetic Polyoxime Malaria Vaccine Containing Plasmodium falciparum B Cell and Universal T Cell Epitopes Elicits Immune Responses in Volunteers of Diverse HLA Types

T cell responses to hepatitis B surface antigen are detectable in non-vaccinated individuals

Intradermal Recombinant Hepatitis B Vaccine for Healthcare Workers Who Fail to Respond to Intramuscular Vaccine

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