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Epitope-targeting platform for broadly protective influenza vaccines
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Journal Article
Epitope-targeting platform for broadly protective influenza vaccines
2021
Overview
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.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Animals
/ Antibodies, Viral - immunology
/ Antigens
/ Epitopes
/ Hemagglutinin Glycoproteins, Influenza Virus - immunology
/ Homology
/ Humans
/ Influenza B virus - immunology
/ Influenza, Human - immunology
/ Influenza, Human - prevention & control
/ Medicine and Health Sciences
/ Mice
/ Orthomyxoviridae Infections - immunology
/ Orthomyxoviridae Infections - virology
/ Peptides
/ Proteins
/ Research and Analysis Methods
/ Vaccines
/ Viruses
