CD4⁺ 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: Adolescent; Adult; Aged; Antibodies; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Applied microbiology; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; Epitopes; Female; Fundamental and applied biological sciences. Psychology; Humans; Immunodominant Epitopes - immunology; Infectious diseases; Influenza; Influenza A Virus, H1N1 Subtype - immunology; Influenza vaccines; Influenza Vaccines - immunology; Influenza, Human - prevention & control; Influenza, Human - virology; Lymphocyte Activation; Major and Brief Reports; Male; Medical sciences; Microbiology; Middle Aged; Neutralizing antibodies; Orthomyxoviridae; Pandemics; Predictive Value of Tests; T lymphocytes; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Inactivated - immunology; Viruses; Young Adult
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jis684

Background. The ability of influenza vaccines to elicit CD4⁺ T cells and the relationship between induction of CD4⁺ 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⁺ T-cell and antibody responses of human subjects vaccinated with monovalent subunit A(H1N1)pdm09 vaccine. The specificity and magnitude of the CD4⁺ 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⁺ T cells specific for conserved portions of hemagglutinin (HA) and the internal viral proteins. Interestingly, expansion of HA-specific CD4⁺ T cells was most tightly correlated with the antibody response. Conclusions. These results indicate that CD4⁺ 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⁺ T cell recruitment may increase the neutralizing antibody produced in response to vaccines against novel influenza strains.