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Clinical and serologic responses to inactivated influenza virus vaccines were studied in 444 children in Los Angeles under doubld-blind, placebo-controlled protocols. One- and two-dose regimens employing monovalent (A/New Jersey/76) and bivalent (A/New Jersey/76-A/Victoria/75) vaccine were studied in separate trials. In a single dose, whole-virus vaccines were more potent than split-product vaccines as primary inducers of immunity against influenza A/New Jersey/76 virus. Split-product vaccines were better tolerated clinically and, after two-dose regiments, produced rates of seroconversion (greater than 90%) against A/New Jersey/76 virus comparable to those produced by two doses of whole-virus vaccines. Analysis of heterotypic antibody responses induced by monovalent A/New Jersey/76 vaccines revealed only slight increases in antibody against influenza A/Victoria/75 virus. After vaccination with bivalent vaccines, levels of antibody against influenza A/Victoria/75 virus were significantly higher in subjects who received high doses of split-product vaccines than in subjects who received whole-virus vaccines.

The character of the immune response to inactivated monovalent influenza A/New Jersey/76 and bivalent influenza A/New Jersey/76-A/Victoria/75 vaccines was studied in children six months to 18 years of age. Titers of hemagglutination-inhibiting antibody in sera taken after vaccination were measured before and after treatment with 2-mercaptoethanol. IgG antibody predominated in responses to the influenza A/Victoria/75 component of bivalent vaccines. In contrast, specific IgM antibody to influenza A/New Jersey/76 virus developed after administration of both monovalent and bivalent vaccines and appeared to characterize the immune response to this antigenic "shift" strain in children. Prevalences of IgM antibody against influenza A/New Jersey/76 virus did not differ significantly by age. This finding implies that type rather than extent of previous experience with influenza determines the IgM antibody response to an antigenic "shifts." Split-product vaccines produced significantly fewer IgM antibody responses to influenza A/New Jersey/76 virus than did whole-virus vaccines, a phenomenon that may correlate with their diminished reactogenicity and immunogenicity in children.