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Heterologous hemagglutination-inhibiting (HAI) antibody responses to influenza A/New Jersey/76 (Hsw1N1) virus vaccine were examined in individuals receiving doses of 200, 400, or 800 chick cell-agglutinating units of whole-virus or split-virus products during the 1976 National Influenza Vaccine Test Program. Vaccination with influenza A/New Jersey/76 virus produced a high rate of heterologous antibody response to influenza A/PR/8/34 (H0N1) and A/FM/1/47 (H1N1) viruses in persons whose original antigenic experience according to their age was with H0N1 or H1N1 strains, respectively. Vaccination with A/New Jersey/76 virus produced only low levels of HAI antibody to influenza A/Japan/305/57 (H2N2) and A/Victoria/3/75 (H3N2) viruses, and these responses were less clearly related to primary infections. Thus the greatest heterologous HAI antibody responses occurred when there were shared antigenic determinants between the hemagglutinins of the vaccine virus and the viruses that had caused the initial priming infection. However, when vaccinations or infections with H3N2 and Hsw1N1 strains may both be occurring in the population, even infrequent formation of heterologous antibody may make it difficult to interpret serologic data precisely.
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