Paradoxical response to a novel influenza virus vaccine strain: the effect of prior immunization

Vaccine. 1999 May 4;17(18):2284-9. doi: 10.1016/s0264-410x(98)00478-2.


Background: repeated influenza immunization does not appear to adversely affect the serum antibody response to new influenza strains.

Objective: to determine whether the immune response to a new influenza strain was inferior in persons previously vaccinated compared with persons not previously vaccinated.

Design: randomized, double-blind clinical trial.

Setting: university affiliated community teaching hospital.

Patients: 139 healthy adult men and women, mean age 38 years.

Intervention: subjects were vaccinated as part of another study. They received influenza vaccines containing influenza strains A/Texas/36/91 (H1N1), A/Nanchang/933/95 (H3N2) and B/Beijing/184/93. One group received a licensed influenza vaccine while the other group received a similar vaccine except the A/Nanchang strain had a diminished potency.

Measurements: serum hemagglutination inhibition (HAI) antibody titers were determined prior to vaccination and two weeks afterward. If patients had a low postvaccination titer, they were revaccinated and HAI titers were determined two weeks later.

Results: 68 adults received the licensed vaccine and 70 received the subpotent vaccine. The groups were similar with regards to baseline characteristics. Those previously vaccinated had significantly lower postvaccination HAI geometric mean titers (GMTs) for all three vaccine strains (A/Texas--127 vs. 359, p < 0.001, A/Nanchang--31 vs. 93, p < 0.001 and B/Beijing--140 vs. 205, p < 0.05). The percentage of subjects with a presumed protective HAI titer of > or =40 was significantly lower among the previously vaccinated groups only for the new influenza strain, A/Nanchang (55% vs. 80%, p < 0.05). For the other two vaccine strains, the percentage with an HAI titer > or =40 was greater than 90% for both groups.

Conclusions: the decrease in serologic response to influenza vaccine among healthy, young adults who were previously vaccinated appears to be unique for this year's influenza vaccine. Further studies are required to determine the frequency and clinical significance of this phenomenon observed in younger healthy adults, and whether it is a general one. Based on its proven efficacy, influenza vaccine should continue to be given on an annual basis to high risk children and adults and to all those 65 years or older.

Publication types

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

MeSH terms

  • Adult
  • Antibodies, Viral / blood
  • Female
  • Humans
  • Immunization, Secondary / adverse effects*
  • Influenza, Human / immunology*
  • Male
  • Orthomyxoviridae / immunology*
  • Viral Vaccines / immunology*


  • Antibodies, Viral
  • Viral Vaccines