A(H1N1)pdm09 vaccination of health care workers: improved immune responses in low responders following revaccination

J Infect Dis. 2012 Dec 1;206(11):1660-9. doi: 10.1093/infdis/jis589. Epub 2012 Sep 11.


Background: We conducted a clinical trial in October 2009 to evaluate the immunogenicity of the AS03-adjuvanted influenza vaccine (pH1N1 vaccine) in health care workers (HCWs). By 2 weeks after vaccination, 97% had protective hemagglutinin inhibition (HI) titers (≥ 40) however, 16% were low responders (LR) and failed to maintain a protective response 90 days after vaccination.

Methods: We analyzed the humoral responses (HI, antibody-secreting cell [ASC], and serum immunoglobulin G [IgG]) in 15 LRs and 25 control HCWs. Twelve LRs were revaccinated with the pH1N1 vaccine, and 7 were subsequently vaccinated with the 2010 seasonal trivalent influenza vaccine. We conducted a long-term analysis of the humoral and CD4(+) T-helper (Th) 1 responses.

Results: The LRs had a slower HI antibody response than the control HCWs, with protective antibody titers not reached until 2 weeks after vaccination in the majority of the participants. The LRs also had significantly lower IgG ASCs at day 7 and HA1-specific serum IgG responses at day 21, compared with the control HCWs. Revaccination with the pH1N1 vaccine elicited rapid HI antibody, ASC, memory B cell, and multifunctional CD4(+) Th1 cell responses.

Conclusion: This study shows that revaccination of low-responding HCWs with the pH1N1 vaccine is required for maintaining long-term protection.

Clinical trials registration: NCT01003288.

Publication types

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

MeSH terms

  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • CD4-Positive T-Lymphocytes
  • Cytokines / genetics
  • Cytokines / metabolism
  • Gene Expression Regulation / immunology
  • Hemagglutination Inhibition Tests
  • Humans
  • Immunity, Humoral
  • Immunization, Secondary*
  • Immunoglobulin G / blood
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / immunology*
  • Influenza, Human / prevention & control*


  • Antibodies, Viral
  • Cytokines
  • Immunoglobulin G
  • Influenza Vaccines

Associated data

  • ClinicalTrials.gov/NCT01003288