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

JL Nayak, TF Fitzgerald, KA Richards… - The Journal of …, 2013 - academic.oup.com
JL Nayak, TF Fitzgerald, KA Richards, H Yang, JJ Treanor, AJ Sant
The Journal of infectious diseases, 2013academic.oup.com
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 …
Abstract
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.
Oxford University Press