Human influenza virus challenge identifies cellular correlates of protection for oral vaccination.
Double-Blind Method
Humans
Immunity
Immunity, Cellular
Immunization
Influenza A Virus, H1N1 Subtype
Influenza A virus
Influenza Vaccines
/ immunology
Influenza, Human
/ immunology
L-Selectin
/ metabolism
STAT5 Transcription Factor
/ metabolism
T-Lymphocytes
Vaccination
Vaccines, Inactivated
/ immunology
Virus Shedding
CyTOF
cellular immunity
correlates of protection
influenza challenge study
influenza vaccine
mass cytometry
Journal
Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316
Informations de publication
Date de publication:
08 12 2021
08 12 2021
Historique:
received:
24
05
2021
revised:
16
09
2021
accepted:
21
10
2021
pubmed:
17
11
2021
medline:
19
1
2022
entrez:
16
11
2021
Statut:
ppublish
Résumé
Developing new influenza vaccines with improved performance and easier administration routes hinges on defining correlates of protection. Vaccine-elicited cellular correlates of protection for influenza in humans have not yet been demonstrated. A phase-2 double-blind randomized placebo and active (inactivated influenza vaccine) controlled study provides evidence that a human-adenovirus-5-based oral influenza vaccine tablet (VXA-A1.1) can protect from H1N1 virus challenge in humans. Mass cytometry characterization of vaccine-elicited cellular immune responses identified shared and vaccine-type-specific responses across B and T cells. For VXA-A1.1, the abundance of hemagglutinin-specific plasmablasts and plasmablasts positive for integrin α4β7, phosphorylated STAT5, or lacking expression of CD62L at day 8 were significantly correlated with protection from developing viral shedding following virus challenge at day 90 and contributed to an effective machine learning model of protection. These findings reveal the characteristics of vaccine-elicited cellular correlates of protection for an oral influenza vaccine.
Identifiants
pubmed: 34784508
pii: S1931-3128(21)00473-X
doi: 10.1016/j.chom.2021.10.009
pmc: PMC8665113
mid: NIHMS1754011
pii:
doi:
Substances chimiques
Influenza Vaccines
0
SELL protein, human
0
STAT5 Transcription Factor
0
Vaccines, Inactivated
0
L-Selectin
126880-86-2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1828-1837.e5Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM137936
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM138353
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI057229
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI100627
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare the following competing interests: S.N.T., D.L., N.S.K., and C.J.M. are current or former employees of Vaxart Inc. G.P.N. and D.R.M. have received research funding support from Vaxart Inc. M.A., K.K., and B.B. are current or former employees of WCCT Global. D.R.M. is an unpaid advisor for WCCT Global. Z.B. is an employee of CellCarta. CMS is a scientific advisor to and has received research funding from Enable Medicine, Inc., all outside of this work.
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