Marcy E. Armstrong

Single and booster dose responses to an inactivated hepatitis A virus vaccine: comparison with immune serum globulin prophylaxis

Pre- and postexposure prophylaxis against hepatitis A virus (HAV) infection with immune serum globulin (Ig) is only effective for 4-6 months. We compared the safety, tolerability and immunogenicity of a single i.m. injection of Ig with a single and booster dose of an inactivated hepatitis A virus vaccine (iHAV) in adults. Healthy volunteers (18-50 years) received a single Ig i.m. injection (n = 30), or iHAV i.m. (n = 15) at 0 and 24 weeks, or placebo (n = 4) at the same intervals. Anti-HAV seroconversion was measured by radioimmunoassay (RIA) and neutralizing antibodies by an antigen reduction assay. After Ig injection (0.06 ml/kg), anti-HAV seroconversion occurred in 100% of recipients at week 1, declining to 10% at week 12 and 0% by week 20. In contrast, after a single 25 ng dose, RIA seropositivity in iHAV vaccinees was 80% by week 2, reaching 100% by week 5 and persisted up to week 24, at which time anti-HAV geometric mean titres (GMT) were two fold higher than those seen at week 1 after Ig. Postbooster anti-HAV titres in iHAV recipients rose within 4 weeks to 73-fold greater than the peak GMT seen one week after Ig, and 400-fold higher than GMT at 12 weeks after Ig. Neutralizing antibody titres after iHAV followed a similar pattern, as observed for anti-HAV. iHAV was well tolerated; placebo and vaccine tolerability were indistinguishable, with no serious adverse experiences observed. In conclusion, active vaccination with a single iHAV dose may eventually replace Ig for pre-exposure prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of an Epstein-Barr virus glycoprotein which is antigenically homologous to the varicella-zoster virus glycoprotein II and the herpes simplex virus glycoprotein B

The Epstein-Barr virus (EBV) antigenic homologue of the varicella-zoster virus glycoprotein II and the herpes simplex virus (HSV) glycoprotein B (gB) was identified through cross-reactivity with anti-glycoprotein II and anti-glycoprotein B peptide sera. The homologue is the previously characterized EBV glycoprotein, with an apparent molecular weight of 125,000 Da, which is synthesized late during productive EBV infection and appears to be encoded by the BamHI A EBV fragment. This glycoprotein, but not other EBV proteins, reacted with the antisera in immunoprecipitation experiments and by ELISA. In addition, absorption of the sera with the purified EBV 125-kDa glycoprotein removed the cross-reacting antibody. Whether the EBV gB homologue has the same biological functions associated with HSV gB has yet to be determined.

Safety profile and immunogenicity of an inactivated vaccine derived from an attenuated strain of hepatitis A.

To determine the safety and immunogenicity of an inactivated hepatitis A vaccine, 56 healthy adult volunteers were randomly assigned to receive an intramuscular injection of 6.3, 12.5 or 25 ng of inactivated hepatitis A vaccine or placebo at 0, 2 or 4, and 24 weeks. Adverse reactions occurred with similar frequency in vaccine and placebo recipients and consisted primarily of pain or tenderness at the injection site. By 4 weeks after a single 6.3, 12.5 or 25 ng injection, seven, nine and ten out of ten vaccinees, respectively, had antibody detectable by a HAV AB assay modified to increase its sensitivity tenfold. All vaccinees had antibodies detectable by this assay within 2 weeks of their second inoculation. Geometric mean antibody levels increased with higher doses of vaccine (p = 0.05). Neutralizing antibody was detected within 4 weeks of a single inoculation in all vaccinees. Neutralizing antibody was detected after the third inoculation at dilutions of greater than or equal to 1:2048 in all 12.5 and 25 ng vaccinees. All 19 vaccinees tested at 24 months still had HAV antibodies detectable by a modified HAV AB assay. This inactivated hepatitis A vaccine appears to be well tolerated and immunogenic at doses of 6.3-25 ng. The choice of dose and vaccination schedule may depend on the rapidity with which seroconversion is desired.

Antigenic Analysis of the EBV Major Membrane Protein (gp350/gp220) Expressed in Yeast and Mammalian Cells

The Epstein-Barr virus (EBV) major membrane protein (gp350/gp220) has been identified as the primary mediator of virus-cell receptor interaction (1) and as an inducer of in vitro virus-neutralizing antibody (2,3,4). Under certain circumstances, the purified membrane protein has been shown to confer protection in model primate animals against the effects of EBV infection (5). The protein is highly glycosylated. Fifty percent of its molecular mass is due to carbohydrate. The identification of the gene which codes for gp350/gp220 has allowed for the expression of the protein in bacteria (6), yeast and mammalian cells. Table 1 lists the systems in which expression has been obtained and the structural characteristics of the expressed proteins. See the accompanying papers of this volume for details. In this report, we describe the results of our antigenic analyses of these proteins as well as of the membrane antigen derived from the B95–8 EBV-transformed marmoset lymphoid cell line. The analyses were designed to determine the immunogenic feasibility of each of the antigens as sub-unit vaccine candidates.