CD4 super(+) T-Cell Expansion Predicts Neutralizing Antibody Responses to Monovalent, Inactivated 2009 Pandemic Influenza A(H1N1) Virus Subtype H1N1 Vaccine

• Published in: The Journal of infectious diseases 2013-01, Vol.207 (2), p.297-305
• Main Authors: Nayak, Jennifer L, Fitzgerald, Theresa F, Richards, Katherine A, Yang, Hongmei, Treanor, John J, Sant, Andrea J
• Format: Article
• Language: English
• Subjects: Influenza A virus
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jis684

Background. The ability of influenza vaccines to elicit CD4 super(+) T cells and the relationship between induction of CD4 super(+) T cells and vaccine-induced neutralizing antibody responses has been controversial. The emergence of swine-origin 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) provided a unique opportunity to examine responses to an influenza vaccine composed of both novel and previously encountered antigens and to probe the relationship between B-cell and T-cell responses to vaccination. Methods. We tracked CD4 super(+) T-cell and antibody responses of human subjects vaccinated with monovalent subunit A(H1N1)pdm09 vaccine. The specificity and magnitude of the CD4 super(+) T-cell response was evaluated using cytokine enzyme-linked immunosorbent spot assays in conjugation with peptide pools representing distinct influenza virus proteins. Results. Our studies revealed that vaccination induced readily detectable CD4 super(+) T cells specific for conserved portions of hemagglutinin (HA) and the internal viral proteins. Interestingly, expansion of HA-specific CD4 super(+) T cells was most tightly correlated with the antibody response. Conclusions. These results indicate that CD4 super(+) T-cell expansion may be a limiting factor in development of neutralizing antibody responses to pandemic influenza vaccines and suggest that approaches to facilitate CD4 super(+) T-cell recruitment may increase the neutralizing antibody produced in response to vaccines against novel influenza strains.