A randomized double-blind comparison of five killed hepatitis A vaccine preparations was carried out with eligible medical student and staff volunteers. Vaccines were prepared in MRC-5 cells and formalin-inactivated. Three monthly injections of 1 ml in the deltoid muscle were given. Group A received the CLF strain at a dose of 360 ELISA units (El. U) in 0.5 mg aluminium hydroxide (n = 35). The other groups received the HM1 75 strain as follows: 180 El. U in 1 mg aluminium hydroxide (to group B, n = 42), 360 El. U in 0.5 mg aluminium hydroxide (to group C, n = 40), 360 El. U in 1 mg aluminium hydroxide (to group D, n = 39) and 720 El. U in 1 mg aluminium hydroxide (to group E, n = 43). The geometric mean anti-HAV concentration (GMC) measured in mIV/ml by an ELISA method one month after each injection were: group A, 223, 480, 1635; group B, 123, 221, 649; group C, 185, 365, 1085; group D, 144, 323, 1076; group E, 229, 646, 2521. At month 6, the GMC had fallen by almost-equal-to 20%. Seroconversion as measured by ELISA was 100% in groups A and E after one injection, and 100% in all groups after three injections; after two injections, only one subject in group C was still negative. The dose effect with HM175 vaccine was significant. There was a good correlation between ELISA and neutralization (radioimmunofocus inhibition test) titres. One month after the second dose, all subjects in groups A and E had both hepatitis A virus immunoglobulin M (HAV IgM) geometric mean titre, (GMT > 5000) and IgG (GMT > 25 000) as measured by a sensitive terminal dilution ELISA. All subjects in groups A and E became positive in the Abbott total anti-HA V radioimmunoassay, although at a titre lower than that after natural infection. Vaccinees in this study were negative in the Abbott IgM radioimmunoassay. Side effects were frequent but negligible, and essentially attributable to the aluminium adjuvant. Based on these results, and because the yield in cell culture of the HM175 strain was better than that of the CLF strain, a 720 El. U dose of HM1 75 was chosen as the standard vaccine formulation. In view of the exceptionally powerful response after a single dose of this vaccine (seroconversion 100% in this study and almost 100% in combined studies) two injections as a primary immunization course, plus a booster, give a satisfactory response.
