Epitope-targeting platform for broadly protective influenza vaccines.

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 p...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	David F Zeigler, Emily Gage, Christopher H Clegg
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d8ef46c113354e9abff9adbbc0fb7f49
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d8ef46c113354e9abff9adbbc0fb7f49
record_format	dspace
spelling	oai:doaj.org-article:d8ef46c113354e9abff9adbbc0fb7f492021-11-25T06:23:40ZEpitope-targeting platform for broadly protective influenza vaccines.1932-620310.1371/journal.pone.0252170https://doaj.org/article/d8ef46c113354e9abff9adbbc0fb7f492021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0252170https://doaj.org/toc/1932-6203Seasonal 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 5LD50 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 >104-fold reduction in pulmonary viral load. These studies describe a compelling platform for building vaccines that target conserved influenza epitopes.David F ZeiglerEmily GageChristopher H CleggPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0252170 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q David F Zeigler Emily Gage Christopher H Clegg Epitope-targeting platform for broadly protective influenza vaccines.
description	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 5LD50 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 >104-fold reduction in pulmonary viral load. These studies describe a compelling platform for building vaccines that target conserved influenza epitopes.
format	article
author	David F Zeigler Emily Gage Christopher H Clegg
author_facet	David F Zeigler Emily Gage Christopher H Clegg
author_sort	David F Zeigler
title	Epitope-targeting platform for broadly protective influenza vaccines.
title_short	Epitope-targeting platform for broadly protective influenza vaccines.
title_full	Epitope-targeting platform for broadly protective influenza vaccines.
title_fullStr	Epitope-targeting platform for broadly protective influenza vaccines.
title_full_unstemmed	Epitope-targeting platform for broadly protective influenza vaccines.
title_sort	epitope-targeting platform for broadly protective influenza vaccines.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/d8ef46c113354e9abff9adbbc0fb7f49
work_keys_str_mv	AT davidfzeigler epitopetargetingplatformforbroadlyprotectiveinfluenzavaccines AT emilygage epitopetargetingplatformforbroadlyprotectiveinfluenzavaccines AT christopherhclegg epitopetargetingplatformforbroadlyprotectiveinfluenzavaccines
_version_	1718413772720177152

Epitope-targeting platform for broadly protective influenza vaccines.

Ejemplares similares