In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 5 ( 2021-5-27), p. e0252170-
Abstract:
Seasonal influenza vaccines are often ineffective because they elicit strain-specific antibody responses to mutation-prone sites on the hemagglutinin (HA) head. Vaccines that provide long-lasting immunity to conserved epitopes are needed. Recently, we reported a nanoparticle-based vaccine platform produced by solid-phase peptide synthesis (SPPS) for targeting linear and helical protein-based epitopes. Here, we illustrate its potential for building broadly protective influenza vaccines. Targeting known epitopes in the HA stem, neuraminidase (NA) active site, and M2 ectodomain (M2e) conferred 50–75% survival against 5LD 50 influenza B and H1N1 challenge; combining stem and M2e antigens increased survival to 90%. Additionally, protein sequence and structural information were employed in tandem to identify alternative epitopes that stimulate greater protection; we report three novel HA and NA sites that are highly conserved in type B viruses. One new target in the HA stem stimulated 100% survival, highlighting the value of this simple epitope discovery strategy. A candidate influenza B vaccine targeting two adjacent HA stem sites led to 〉 10 4 -fold reduction in pulmonary viral load. These studies describe a compelling platform for building vaccines that target conserved influenza epitopes.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0252170
DOI:
10.1371/journal.pone.0252170.g001
DOI:
10.1371/journal.pone.0252170.g002
DOI:
10.1371/journal.pone.0252170.g003
DOI:
10.1371/journal.pone.0252170.g004
DOI:
10.1371/journal.pone.0252170.s001
DOI:
10.1371/journal.pone.0252170.s002
DOI:
10.1371/journal.pone.0252170.s003
DOI:
10.1371/journal.pone.0252170.s004
DOI:
10.1371/journal.pone.0252170.s005
DOI:
10.1371/journal.pone.0252170.s006
DOI:
10.1371/journal.pone.0252170.s007
DOI:
10.1371/journal.pone.0252170.s008
DOI:
10.1371/journal.pone.0252170.s009
DOI:
10.1371/journal.pone.0252170.s010
DOI:
10.1371/journal.pone.0252170.s011
DOI:
10.1371/journal.pone.0252170.s012
DOI:
10.1371/journal.pone.0252170.s013
DOI:
10.1371/journal.pone.0252170.s014
DOI:
10.1371/journal.pone.0252170.r001
DOI:
10.1371/journal.pone.0252170.r002
DOI:
10.1371/journal.pone.0252170.r003
DOI:
10.1371/journal.pone.0252170.r004
DOI:
10.1371/journal.pone.0252170.r005
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
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