Intranasal live influenza vaccine priming elicits localized B cell responses in mediastinal lymph nodes

Sinthujan Jegaskand, Rosemarie D. Mason, Sarah F. Andrews, Adam K. Wheatley, Ruijun Zhang, Glennys V. Reynoso, David R. Ambrozak, Celia P. Santos, Catherine J. Luke, Yumiko Matsuoka, Jason M. Brenchley, Heather D. Hickman, Kawsar R. Talaat, Sallie R. Permar, Hua Xin Liao, Jonathan W. Yewdell, Richard A. Koup, Mario Roederer, Adrian B. McDermott, Kanta Subbarao

Research output: Contribution to journalArticle

Abstract

Pandemic live attenuated influenza vaccines (pLAIV) prime subjects for a robust neutralizing antibody response upon subsequent administration of a pandemic inactivated subunit vaccine (pISV). However, a difference was not detected in H5-specific memory B cells in the peripheral blood between pLAIV-primed and unprimed subjects prior to pISV boost. To investigate the mechanism underlying pLAIV priming, we vaccinated groups of 12 African green monkeys (AGMs) with H5N1 pISV or pLAIV alone or H5N1 pLAIV followed by pISV and examined immunity systemically and in local draining lymph nodes (LN). The AGM model recapitulated the serologic observations from clinical studies. Interestingly, H5N1 pLAIV induced robust germinal center B cell responses in the mediastinal LN (MLN). Subsequent boosting with H5N1 pISV drove increases in H5-specific B cells in the axillary LN, spleen, and circulation in H5N1 pLAIV-primed animals. Thus, H5N1 pLAIV primes localized B cell responses in the MLN that are recalled systemically following pISV boost. These data provide mechanistic insights for the generation of robust humoral responses via prime-boost vaccination.

Original languageEnglish (US)
Article numbere01970-17
JournalJournal of virology
Volume92
Issue number9
DOIs
StatePublished - May 1 2018

Keywords

  • B cells
  • Influenza
  • LAIV
  • Vaccines

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Jegaskand, S., Mason, R. D., Andrews, S. F., Wheatley, A. K., Zhang, R., Reynoso, G. V., Ambrozak, D. R., Santos, C. P., Luke, C. J., Matsuoka, Y., Brenchley, J. M., Hickman, H. D., Talaat, K. R., Permar, S. R., Liao, H. X., Yewdell, J. W., Koup, R. A., Roederer, M., McDermott, A. B., & Subbarao, K. (2018). Intranasal live influenza vaccine priming elicits localized B cell responses in mediastinal lymph nodes. Journal of virology, 92(9), [e01970-17]. https://doi.org/10.1128/JVI.01970-17