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Local B-cell #immunity and durable memory following live-attenuated #influenza intranasal #vaccination of #humans

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By G.M.

Abstract

Seasonal influenza vaccines are most frequently delivered as intramuscular inactivated vaccines which elicit systemic responses against the immunodominant hemagglutinin (HA) head domain. An intranasally administered, live-attenuated influenza vaccine designed to stimulate mucosal immunity, FluMist, is the sole intranasal vaccine approved in the United States. However, FluMist has lower systemic immunogenicity and efficacy in adults compared to intramuscular formulations. In this study, human mucosal and systemic immunity were examined following seasonal intramuscular or intranasal vaccination. Nasopharyngeal swabs of adenoid tissue were used to longitudinally sample the upper airway. Notably, FluMist induced substantial increases in upper respiratory tract IgG+ and IgA+ HA-specific memory B cells, which displayed an activated CD27+CD21- phenotype. H1, H3, and influenza B virus HA-specific memory B cells were all detected in the upper airway after intranasal immunization and remained elevated at 6-months post-vaccination. Recently activated upper airway memory B cells were not readily detected in intramuscular vaccinees, despite marked elevation of systemic antibody and memory B cells. Thus, despite minimal immune response detected in circulation, live-attenuated influenza vaccine can generate substantial local antigen-specific memory B cell responses in adults. These findings have implications for improving influenza vaccines and for mucosal vaccination against other respiratory pathogens.


Competing Interest Statement

S.C. has no competing interests related to influenza vaccines. The other authors declare no competing interests. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays, NDV-based SARS-CoV-2 vaccines influenza virus vaccines and influenza virus therapeutics which list FK as co-inventor and FK has received royalty payments from some of these patents. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2 and another company, Castlevax, to develop SARS-CoV-2 vaccines. FK is co-founder and scientific advisory board member of Castlevax. FK has consulted for Merck, GSK, Sanofi, Curevac, Gritstone, Seqirus and Pfizer and is currently consulting for 3rd Rock Ventures and Avimex. The Krammer laboratory is also collaborating with Dynavax on influenza vaccine development.


Funder Information Declared

National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH), Department of Health and Human Services, AI142742

NIH NIAID CIVIC, 75N93019C00051

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