Comparative trial of influenza vaccines. I. Immunogenicity of whole virus and split product vaccines in man.

Groups of about 100 persons aged 6 to 88 years were given 1 of 6 commercially prepared whole virus or split-product bivalent (A/England-B/Mass) influenza vaccines and 6 weeks later were given 1 of 5 monovalent (B/Hong Kong) vaccines. Hemagglutination-inhibiting (HI) antibody titers in serum specimens taken 6 and 12 weeks after inoculation were compared to those obtained before immunization. Overall antibody responses in all groups were adequate, yielding HI titers that are associated with relatively good levels of protection from infection. No differences were noted among the vaccines in their ability to boost pre-existing antibody. The tributyl phosphate (TBP) split-product vaccine, however, induced significantly lower homologous seroconversion and geometric mean antibody titers (GMT) to A/England and heterologous antibody titers to A/Aichi in persons without pre-existing antibody than did equivalent whole virus vaccines. Both the TBP and the ether-treated monovalent B/Hong Kong vaccines also induced lower heterologous GMT's to B/Mass in initially seronegative individuals. These data agree with previous observations that the primary response to influenza and other viral vaccines prepared from disrupted virions results in lower levels of antibody than does that to equivalent whole virus preparations. Studies are underway to determine whether the lesser immune response induced by these vaccines in seronegative persons is the result of smaller amounts of antigen in such preparations or because the antigen may be processed less efficiently by humoral or cellular immune mechanisms.