Clinical studies of monovalent inactivated whole virus and subunit A/USSR/77 (H1N1) vaccine: serological responses and clinical reactions

Abstract

The clinical acceptability and antibody responses to graded doses of whole virus, aqueous surface antigen and adsorbed surface antigen influenza A/USSR/92/77 (H1N1) virus vaccines were assessed in 1335 healthy volunteers in a double-blind, multi-centre study conducted in the U.K. in February and March 1978. Before vaccination the presence of haemagglutination-inhibiting (HI) and neuraminidase-inhibiting (NI) serum anti-bodies to the vaccine virus was infrequent and in low titres in volunteers aged ≤ 25 years but was more frequent in older persons. In volunteers aged ≤ 25 years, who were sero-negative for HI antibody before vaccination, the HI antibody responses following one dose of vaccine were generally of low frequency and titre for all doses and types of vaccine. Nevertheless, whole virus or subunit vaccines with high antigenic content (≥ 47 μg haemagglutinin (HA) per dose) induced HI antibody responses in at least 60% of recipients. Following two doses of whole virus, aqueous or adsorbed surface antigen vaccine containing at least 9 μg HA per dose, serum HI titres of ≥ 40 were detected in 69–100% of recipients. In volunteers aged ≥ 26 years, who received a single dose of any of the test vaccines containing at least 3 μg HA, the HI antibody responses were frequent and post vaccine titres of ≥ 40 were detected in 80% of vaccinees. A ‘shallow’ dose response effect over a wide range of antigen concentrations of whole virus (5–94 μg HA per dose) or subunit vaccines was noted for each age group. Both the geometric mean HI antibody titres and proportion of vaccinees developing HI titres ≥ 40 were similar for each age group when comparable doses of vaccine were given by the subcutaneous and intradermal routes. A preliminary study of the NI antibody responses to vaccination indicated that all the whole virus and subunit vaccines stimulated serum NI antibodies in a proportion of recipients. All vaccines were clinically well tolerated.