A Controlled Double-Blind Comparison of Reactogenicity, Immunogenicity, and Protective Efficacy of Whole-Virus and Split-Product Influenza Vaccines in Children

J Infect Dis. 1977 Nov;136(5):623-32. doi: 10.1093/infdis/136.5.623.


A double-blind randomized study with bivalent influenza virus vaccines was conducted to compare the local and systemic reactions and immunogenicity of a whole-virus vaccine and a split-product vaccine in children. Fevers of greater than 100 F were more frequent after vaccination with whole-virus than split-product vaccine especially in children one to four years old (69% vs 22%; P less than 0.01). Fevers of greater than or equal to 103 F did not occur in children who previously had been given influenza virus vaccine, even in the absence of preexisting homologous serum antibody. The immune response to the A/Port Chalmers/1/73 antigen in the vaccine was similar after administration of either whole-virus or split-product vaccine. However, split-product vaccine induced significantly less hemagglutination-inhibiting antibody to B/Hong Kong/5/72 virus in children younger than 10 years who had not been previously immunized; only 43% developed detectable antibody vs. 100% of those vaccinated with whole virus vaccine (P less than 0.01). These studies indicate that (1) in young children whole-virus vaccine causes fever more frequently than split-product vaccine; (2) young children previously vaccinated with influenza virus vaccine are unlikely to experience fever subsequent to immunization with a related antigen; and (3) split-product vaccine induces less antibody to B/Hong Kong/5/72 virus than whole-virus vaccine in immunologically unprimed young children.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antibodies, Viral / biosynthesis*
  • Child
  • Child, Preschool
  • Clinical Trials as Topic
  • Double-Blind Method
  • Fever / etiology
  • Hemagglutination Inhibition Tests
  • Humans
  • Infant
  • Influenza A virus / immunology*
  • Influenza Vaccines* / adverse effects
  • Influenza, Human / prevention & control*


  • Antibodies, Viral
  • Influenza Vaccines