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Vaccine-induced boosting of influenza virus-specific CD4 T cells in younger and aged humans.

Publication ,  Journal Article
Dolfi, DV; Mansfield, KD; Kurupati, RK; Kannan, S; Doyle, SA; Ertl, HCJ; Schmader, KE; Wherry, EJ
Published in: PLoS One
2013

Current yearly influenza virus vaccines induce strain-specific neutralizing antibody (NAb) responses providing protective immunity to closely matched viruses. However, these vaccines are often poorly effective in high-risk groups such as the elderly and challenges exist in predicting yearly or emerging pandemic influenza virus strains to include in the vaccines. Thus, there has been considerable emphasis on understanding broadly protective immunological mechanisms for influenza virus. Recent studies have implicated memory CD4 T cells in heterotypic immunity in animal models and in human challenge studies. Here we examined how influenza virus vaccination boosted CD4 T cell responses in younger versus aged humans. Our results demonstrate that while the magnitude of the vaccine-induced CD4 T cell response and number of subjects responding on day 7 did not differ between younger and aged subjects, fewer aged subjects had peak responses on day 14. While CD4 T cell responses were inefficiently boosted against NA, both HA and especially nucleocaspid protein- and matrix-(NP+M) specific responses were robustly boosted. Pre-existing CD4 T cell responses were associated with more robust responses to influenza virus NP+M, but not H1 or H3. Finally pre-existing strain-specific NAb decreased the boosting of CD4 T cell responses. Thus, accumulation of pre-existing influenza virus-specific immunity in the form of NAb and cross-reactive T cells to conserved virus proteins (e.g. NP and M) over a lifetime of exposure to infection and vaccination may influence vaccine-induced CD4 T cell responses in the aged.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

10

Start / End Page

e77164

Location

United States

Related Subject Headings

  • Viral Proteins
  • Vaccines, Inactivated
  • Species Specificity
  • Orthomyxoviridae
  • Male
  • Kinetics
  • Influenza Vaccines
  • Humans
  • General Science & Technology
  • Female
 

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Dolfi, D. V., Mansfield, K. D., Kurupati, R. K., Kannan, S., Doyle, S. A., Ertl, H. C. J., … Wherry, E. J. (2013). Vaccine-induced boosting of influenza virus-specific CD4 T cells in younger and aged humans. PLoS One, 8(10), e77164. https://doi.org/10.1371/journal.pone.0077164
Dolfi, Douglas V., Kathleen D. Mansfield, Raj K. Kurupati, Senthil Kannan, Susan A. Doyle, Hildegund C. J. Ertl, Kenneth E. Schmader, and E John Wherry. “Vaccine-induced boosting of influenza virus-specific CD4 T cells in younger and aged humans.PLoS One 8, no. 10 (2013): e77164. https://doi.org/10.1371/journal.pone.0077164.
Dolfi DV, Mansfield KD, Kurupati RK, Kannan S, Doyle SA, Ertl HCJ, et al. Vaccine-induced boosting of influenza virus-specific CD4 T cells in younger and aged humans. PLoS One. 2013;8(10):e77164.
Dolfi, Douglas V., et al. “Vaccine-induced boosting of influenza virus-specific CD4 T cells in younger and aged humans.PLoS One, vol. 8, no. 10, 2013, p. e77164. Pubmed, doi:10.1371/journal.pone.0077164.
Dolfi DV, Mansfield KD, Kurupati RK, Kannan S, Doyle SA, Ertl HCJ, Schmader KE, Wherry EJ. Vaccine-induced boosting of influenza virus-specific CD4 T cells in younger and aged humans. PLoS One. 2013;8(10):e77164.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

10

Start / End Page

e77164

Location

United States

Related Subject Headings

  • Viral Proteins
  • Vaccines, Inactivated
  • Species Specificity
  • Orthomyxoviridae
  • Male
  • Kinetics
  • Influenza Vaccines
  • Humans
  • General Science & Technology
  • Female