Evaluation of a new hepatitis B triple-antigen vaccine in inadequate responders to current vaccines

Abstract

In this double-blind, randomized, controlled study, healthcare professionals with a history of inadequate response to currently available single-antigen hepatitis B vaccines confirmed by measuring hepatitis B surface antibody titer before entry to the study were revaccinated with a 20-g dose either of a novel triple-antigen (S, pre-S1, and pre-S2) recombinant vaccine or of a present single-antigen (S only) vaccine. Hepatitis B surface antibody titers were measured 8 weeks' post revaccination. A total of 925 individuals were randomized and vaccinated, of whom 915 (98.9%) completed the study and were included in the efficacy analysis. A single dose of the new triple-antigen hepatitis B vaccine (Hepacare) produced a successful response in over three quarters of these subjects who had not mounted an adequate response to current vaccines. The antibody response was statistically significantly superior (P ‫؍‬ .002) to that after a single dose of current vaccines. An evaluation of the overall response showed that only the triple-antigen vaccine was able to raise the average antibody response (geometric mean titer [GMT]) to over 100 IU/L. The superior effect of the new vaccine was most pronounced in subjects who were previously complete nonresponders to currently available hepatitis B vaccines. Both vaccines were well tolerated and had similar safety profiles. This study demonstrated that in healthcare workers who had responded inadequately to at least a full course of immunization (median, 5 doses), a single 20-g dose of a new triple-antigen vaccine induced protective antibody level in more vaccinees (P ‫؍‬ .002) and increased the average antibody titer (GMT) in those protected successfully to a greater degree (P < . 001) than a further attempt with a current vaccine (Engerix-B). (HEPATOLOGY 2001;34:798-802.)It is estimated that more than 2 billion people worldwide have been infected by the hepatitis B virus (HBV), and that currently there are about 350 million carriers. 1 Vaccination is the only approach to eradication of the disease, and the adoption of universal childhood vaccination against hepatitis B is now recommended 2 and implemented in some 100 countries. However, these programs have only been adopted in the last decade or so, and therefore there is a continuing need to protect those at high risk such as physicians and ancillary healthcare workers. 3 In this context, it is important to recognize that present vaccination programs are not completely successful, and that 10% to 15% of the normal adult population fail to produce hepatitis B surface antibody (anti-HBs) titers above the critical values for protection (10 IU/L). 4,5 The HBV consists of an inner core and an outer surface coat (hepatitis B surface antigen [HBsAg]). The inner core contains double-stranded DNA, DNA polymerase, hepatitis B core antigen, and the e antigen. Several antigenic determinants (a, d, y, w, and r) are found on HBsAg particles. The HBV genome consists of several open reading frames in addition to that for the common surface antigen...

Hydrogel-Delivered GM-CSF Overcomes Nonresponsiveness to Hepatitis B Vaccine through the Recruitment and Activation of Dendritic Cells

“…Studies using overlapping peptides revealed that the pre-S region was important for eliciting T cell responses and, thus, help to improve the immunogenicity of the PreS/S vaccine (60). However, the enhanced immunogenicity was only observed for mammalian cell-produced PreS/S vaccines (57), not for yeastderived PreS/S vaccines (58,59), suggesting that glycosylation might also play a role in the improved immunogenicity. The expected high cost of the mammalian-produced vaccine will limit its clinical application.…”

“…HBsAg-pulsed DCs, a cellbased vaccine, was reported to induce anti-HBs Abs in HBsAg vaccine nonresponders (54). The pre-S-containing HBsAg (PreS/ S) vaccine, with addition of the pre-S1 and pre-S2 sequences to the S protein, helped to circumvent immune nonresponsiveness to HBsAg in B10.M mice (55,56) and in several human clinical trials (57)(58)(59). Studies using overlapping peptides revealed that the pre-S region was important for eliciting T cell responses and, thus, help to improve the immunogenicity of the PreS/S vaccine (60).…”

Serologic and Molecular Characteristics of Hepatitis B Virus among School Children in East Java, Indonesia

“…In Indonesia, recombinant hepatitis B -L62 +/+ S113T T126I, T143S --L119 -/+ K24R,Q56P,I57T,C64S, S113T T126I, T143S --vaccines that include pre-S1 and pre-S2 regions currently unavailable. However, this new triple-antigen vaccine is more efficient than the single-antigen vaccine, 20,21 and prevents infection from vaccine-escape mutants. 22 The triple-antigen vaccine should be considered in our study area where the prevalence of anti-HBs remains insufficient among children.…”

Immunogenicity of an investigational hepatitis B vaccine (hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide) in nonresponders to licensed hepatitis B vaccine

“…18 A high-antigen-content vaccine with a novel adjuvant (MPL plus alum; AS04) is also associated with higher seroprotective rates and geometric mean antibody levels in nonresponders. 12,18 Other novel vaccines, including a triple-antigen HBsAg vaccine (S, pre-S1, pre-S2) 13,17 and a DNA vaccine, 16 have demonstrated improved efficacy in nonresponders. Multisite revaccination with HBsAg-Eng vaccine via the intradermal route can also induce seroconversion in some nonresponders.…”