title: Safety profile and immunogenicity of an inactivated vaccine derived from an attenuated strain of hepatitis A.
abstract: 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.
authors.affiliation: Center for Immunization Research, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD 21205.
authors.forename: E F
authors.initials: EF
authors.lastname: Ellerbeck
authors.forename: J A
authors.initials: JA
authors.lastname: Lewis
authors.forename: D
authors.initials: D
authors.lastname: Nalin
authors.forename: K
authors.initials: K
authors.lastname: Gershman
authors.forename: W J
authors.initials: WJ
authors.lastname: Miller
authors.forename: M E
authors.initials: ME
authors.lastname: Armstrong
authors.forename: J P
authors.initials: JP
authors.lastname: Davide
authors.forename: A E
authors.initials: AE
authors.lastname: Rhoad
authors.forename: B
authors.initials: B
authors.lastname: McGuire
authors.forename: G
authors.initials: G
authors.lastname: Calandra
mesh_terms: D000293:Adolescent; D000328:Adult; D000956:Antigens, Viral / Q000302:isolation & purification; D004341:Drug Evaluation; D005260:Female; D005557:Formaldehyde; D006506:Hepatitis A / Q000276:immunology*; D022362:Hepatitis A Vaccines; D006508:Hepatitis Antibodies / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D015164:Vaccines, Inactivated / Q000009:adverse effects / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000009:adverse effects* / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D022362:Hepatitis A Vaccines; D006508:Hepatitis Antibodies; D015164:Vaccines, Inactivated; D014761:Viral Hepatitis Vaccines; D005557:Formaldehyde