BioDrugs

, Volume 7, Issue 3, pp 232–248

Virosomal Hepatitis A Vaccine (Strain RG-SB)

A Preliminary Review of its Immunogenicity, Protective Efficacy and Tolerability in At-Risk Populations
Adis Drug Evaluation

DOI: 10.2165/00063030-199707030-00006

Cite this article as:
Lea, A.P. & Balfour, J.A. BioDrugs (1997) 7: 232. doi:10.2165/00063030-199707030-00006

Summary

Synopsis

Virosomal hepatitis A vaccine contains formalin-inactivated hepatitis A (strain RG-SB) antigen adsorbed on to immunopotentiating reconstituted influenza virosomes (IRIVs). IRIVs act as an adjuvant and may stimulate both the cell-mediated and humoral immune responses to vaccine antigens.

In noncomparative studies, virosomal hepatitis A vaccine (500 radioimmunoassay units) has exhibited immunogenicity in adults and children, inducing seroconversion in almost all volunteers within 4 weeks (usually within 2 weeks) of vaccination. Booster injections of the virosomal vaccine 12 months after the initial dose increased anti-hepatitis A virus (anti-HAV) antibody titres by 11- to 39- fold. Studies of up to 3 years in duration (with a booster vaccination after 1 year) have shown high anti-HAV antibody titres; protection against hepatitis A infection has been estimated to last for 8 to 12.5 years and an unpublished report suggests that 68% of vaccinees may be protected for ⩾30 years. In comparative studies, the virosomal vaccine produced lower anti-HAV antibody titres than an aluminium hydroxide-adsorbed vaccine (strain HM175), but similar percentages of volunteers seroconverted.

The virosomal vaccine was shown to have 95% protective efficacy in unpublished preliminary results of a randomised double-blind trial involving Nicaraguan children. The vaccine had better local tolerability than an aluminium hydroxide-adsorbed hepatitis A (strain HM175) vaccine in immunogenicity studies. The most common adverse effect was pain or soreness at the injection site.

Thus, virosomal hepatitis A vaccine (strain RG-SB) is highly immunogenic, has demonstrated protection from hepatitis A infection in a preliminary report, and appears to have a relatively low incidence of local adverse effects on injection. The final placement of this vaccine in the prevention of hepatitis A infection will be determined by the duration of protection it offers in comparison to other hepatitis A vaccines and its relative acquisition costs.

Formulation and Immunogenicity

Virosomal hepatitis A vaccine consists of formalin-inactivated hepatitis A virions (strain RG-SB) adsorbed on to immunopotentiating reconstituted influenza virosomes (IRIVs). When used as an antigen delivery system for vaccines, IRIVs may stimulate both cell-mediated and humoral immune responses to vaccine antigens.

A single dose of 500 radioimmunoassay units (RU) of this virosomal hepatitis A vaccine induced seroconversion [⩾20 enzyme-linked immunosorbent assay (ELISA) units per litre of anti-hepatitis A virus (anti-HAV) antibodies] in the majority of adult volunteers after 2 weeks and in virtually all after 4 weeks in noncomparative studies. After 1 year, 96 to 100% of volunteers were still seropositive. Similar seroconversion rates were observed in children.

A booster dose of the virosomal vaccine increased anti-HAV antibody titres by 11- to 39-fold following initial vaccination with either the virosomal vaccine or an aluminium hydroxide-adsorbed hepatitis A vaccine (strain HM175) administered 1 year previously. 100% of volunteers seroconverted following administration of a booster injection.

Persistence of anti-HAV antibody has been demonstrated for up to 3 years after an initial vaccination with the virosomal vaccine 500RU followed by a 12-month booster vaccination. On the basis of the rate of decline of anti-HAV antibody titres, the duration of protection against hepatitis A infection has been estimated to be 8 to 12.5 years. In an unpublished report, using a new analytical method based on the rate of decline of anti-HAV antibody titres between 2 and 3 years post-booster, it was estimated that protection may last for ⩾30 years in 68% of vaccinees.

In 2 comparative studies, recipients of initial and booster doses of an aluminium hydroxide-adsorbed vaccine (strain HM175; 1440 and 1440 or 720 ELISA units) had significantly higher anti-HAV antibody titres than those vaccinated with initial and booster doses of the virosomal vaccine (500RU and 500RU). However, there were no significant differences between the vaccines with regard to the percentages of volunteers who seroconverted.

Protective Efficacy

In preliminary reports of a randomised double-blind placebo-controlled trial conducted in children from a region of Nicaragua endemic with hepatitis A, 1 of 122 recipients of the virosomal vaccine was shown to be infected with hepatitis A, compared with 20 of 119 placebo recipients. Thus, the protective efficacy of the virosomal vaccine is estimated as 95% with a 95% confidence interval of 64 to 99%, although final results are yet to be published.

Pharmacoeconomic Considerations

Several pharmacoeconomic analyses have investigated the use of hepatitis A vaccines in general and the results appear to be applicable to use of the virosomal vaccine. Hepatitis A vaccination is more cost effective than passive immunisation for travellers journeying from areas of low hepatitis A endemicity to areas of moderate to high endemicity when the trips are of long duration (⩾6 months) or multiple trips (⩾3) are made over a 10-year period. However, neither intervention was found to be cost effective when compared with non-intervention (i.e. the costs of treating patients with hepatitis A in an unvaccinated population).

The cost effectiveness of hepatitis A vaccination in military personnel was similar to that in travellers. When troops are deployed from areas of low hepatitis A endemicity to areas of high endemicity, active vaccination is more cost effective than passive vaccination only if troops are likely to be deployed more than once, or as in one study of French military service volunteers, in those expecting an extended stay.

However, the results of a retrospective cost-benefit analysis of the occurrence of hepatitis A in Swiss flightcrews indicate that vaccination of male flight attendants and pilots travelling to developing countries would be cost saving to the airline compared with non-intervention.

Tolerability

The virosomal hepatitis A vaccine is well tolerated. Preliminary results of a field trial which determined protective efficacy in children showed that mild local adverse effects were experienced by 14% of vaccine recipients compared with 8% of placebo recipients.

In comparative clinical trials, the virosomal vaccine was associated with significantly lower incidences of local injection site events than an aluminium hydroxide-adsorbed hepatitis A vaccine (strain HM175). The most frequent adverse event associated with the virosomal vaccine, pain or soreness, was experienced by 12 to 26% of recipients compared with 36 to 65% of recipients of the aluminium-adsorbed vaccine. Other local adverse events with the virosomal vaccine included induration, redness and swelling. The incidence of systemic adverse events (fever, headache, malaise, gastrointestinal events and anorexia occurring in ⩽20% of volunteers) was similar with the 2 types of vaccine.

Dosage and Administration

Virosomal hepatitis A vaccine should be administered by injection into the deltoid muscle of the arm. The recommended dosage for both children and adults is a single injection of 0.5ml of vaccine containing 500RU of antigen. A booster injection may be administered Administration ⩾1 year after the initial vaccination.

Copyright information

© Adis International Limited 1997

Authors and Affiliations

  1. 1.Adis International LimitedMairangi Bay, Auckland 10New Zealand

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