@article{eef733e4c4ff4926adea480fdfe2fa62,
title = "Intranasal live influenza vaccine priming elicits localized B cell responses in mediastinal lymph nodes",
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.",
keywords = "B cells, Influenza, LAIV, Vaccines",
author = "Sinthujan Jegaskand and Mason, {Rosemarie D.} and Andrews, {Sarah F.} and Wheatley, {Adam K.} and Ruijun Zhang and Reynoso, {Glennys V.} and Ambrozak, {David R.} and Santos, {Celia P.} and Luke, {Catherine J.} and Yumiko Matsuoka and Brenchley, {Jason M.} and Hickman, {Heather D.} and Talaat, {Kawsar R.} and Permar, {Sallie R.} and Liao, {Hua Xin} and Yewdell, {Jonathan W.} and Koup, {Richard A.} and Mario Roederer and McDermott, {Adrian B.} and Kanta Subbarao",
note = "Funding Information: We declare that we have no conflicts of interest. We are grateful to Ata Mohammed Rasheed and Rafi Ahmed for technical advice. We thank Ashley Majewski, Joanna Swerczek, and Richard Herbert of the National Institutes of Health Animal Center (NIAID) for technical assistance and Margaret Beddall and Pratip Chattopadhyay for reagents (Vaccine Research Center, NIAID). This research is supported in part by the Intramural Research Program of NIAID, NIH. S.J. is supported by a National Health and Medical Research Council, Australia Early Career Fellowship (APP1072127). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. S.J., K.S., R.D.M., S.F.A., A.K.W., and A.B.M. designed the study. S.J., R.D.M., C.L., K.T., J.M.B., R.A.K., M.R., H.-X.L., and Y.M. performed assays, and analysis and C.S. and D.A. provided technical assistance. R.D.M., R.Z., S.R.P., and H.-X.L. performed sequence analysis. G.R., J.W.Y., and H.D.H. performed microscopy Publisher Copyright: {\textcopyright} 2018 American Society for Microbiology.",
year = "2018",
month = may,
day = "1",
doi = "10.1128/JVI.01970-17",
language = "English (US)",
volume = "92",
journal = "Journal of virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "9",
}