Nonreplicating Influenza A Virus Vaccines Confer Broad Protection against Lethal Challenge

ABSTRACT New vaccine technologies are being investigated for their ability to elicit broadly cross-protective immunity against a range of influenza viruses. We compared the efficacies of two intranasally delivered nonreplicating influenza virus vaccines (H1 and H5 S-FLU) that are based on the suppre...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Mariana Baz, Kobporn Boonnak, Myeisha Paskel, Celia Santos, Timothy Powell, Alain Townsend, Kanta Subbarao
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/79a9b26e4bc64166a35f0eb2fe4f499e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:79a9b26e4bc64166a35f0eb2fe4f499e
record_format	dspace
spelling	oai:doaj.org-article:79a9b26e4bc64166a35f0eb2fe4f499e2021-11-15T15:41:31ZNonreplicating Influenza A Virus Vaccines Confer Broad Protection against Lethal Challenge10.1128/mBio.01487-152150-7511https://doaj.org/article/79a9b26e4bc64166a35f0eb2fe4f499e2015-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01487-15https://doaj.org/toc/2150-7511ABSTRACT New vaccine technologies are being investigated for their ability to elicit broadly cross-protective immunity against a range of influenza viruses. We compared the efficacies of two intranasally delivered nonreplicating influenza virus vaccines (H1 and H5 S-FLU) that are based on the suppression of the hemagglutinin signal sequence, with the corresponding H1N1 and H5N1 cold-adapted (ca) live attenuated influenza virus vaccines in mice and ferrets. Administration of two doses of H1 or H5 S-FLU vaccines protected mice and ferrets from lethal challenge with homologous, heterologous, and heterosubtypic influenza viruses, and two doses of S-FLU and ca vaccines yielded comparable effects. Importantly, when ferrets immunized with one dose of H1 S-FLU or ca vaccine were challenged with the homologous H1N1 virus, the challenge virus failed to transmit to naive ferrets by the airborne route. S-FLU technology can be rapidly applied to any emerging influenza virus, and the promising preclinical data support further evaluation in humans. IMPORTANCE Influenza viruses continue to represent a global public health threat, and cross-protective vaccines are needed to prevent seasonal and pandemic influenza. Currently licensed influenza vaccines are based on immunity to the hemagglutinin protein that is highly variable. However, T cell responses directed against highly conserved viral proteins contribute to clearance of the virus and confer broadly cross-reactive and protective immune responses against a range of influenza viruses. In this study, two nonreplicating pseudotyped influenza virus vaccines were compared with their corresponding live attenuated influenza virus vaccines, and both elicited robust protection against homologous and heterosubtypic challenge in mice and ferrets, making them promising candidates for further evaluation in humans.Mariana BazKobporn BoonnakMyeisha PaskelCelia SantosTimothy PowellAlain TownsendKanta SubbaraoAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 5 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Mariana Baz Kobporn Boonnak Myeisha Paskel Celia Santos Timothy Powell Alain Townsend Kanta Subbarao Nonreplicating Influenza A Virus Vaccines Confer Broad Protection against Lethal Challenge
description	ABSTRACT New vaccine technologies are being investigated for their ability to elicit broadly cross-protective immunity against a range of influenza viruses. We compared the efficacies of two intranasally delivered nonreplicating influenza virus vaccines (H1 and H5 S-FLU) that are based on the suppression of the hemagglutinin signal sequence, with the corresponding H1N1 and H5N1 cold-adapted (ca) live attenuated influenza virus vaccines in mice and ferrets. Administration of two doses of H1 or H5 S-FLU vaccines protected mice and ferrets from lethal challenge with homologous, heterologous, and heterosubtypic influenza viruses, and two doses of S-FLU and ca vaccines yielded comparable effects. Importantly, when ferrets immunized with one dose of H1 S-FLU or ca vaccine were challenged with the homologous H1N1 virus, the challenge virus failed to transmit to naive ferrets by the airborne route. S-FLU technology can be rapidly applied to any emerging influenza virus, and the promising preclinical data support further evaluation in humans. IMPORTANCE Influenza viruses continue to represent a global public health threat, and cross-protective vaccines are needed to prevent seasonal and pandemic influenza. Currently licensed influenza vaccines are based on immunity to the hemagglutinin protein that is highly variable. However, T cell responses directed against highly conserved viral proteins contribute to clearance of the virus and confer broadly cross-reactive and protective immune responses against a range of influenza viruses. In this study, two nonreplicating pseudotyped influenza virus vaccines were compared with their corresponding live attenuated influenza virus vaccines, and both elicited robust protection against homologous and heterosubtypic challenge in mice and ferrets, making them promising candidates for further evaluation in humans.
format	article
author	Mariana Baz Kobporn Boonnak Myeisha Paskel Celia Santos Timothy Powell Alain Townsend Kanta Subbarao
author_facet	Mariana Baz Kobporn Boonnak Myeisha Paskel Celia Santos Timothy Powell Alain Townsend Kanta Subbarao
author_sort	Mariana Baz
title	Nonreplicating Influenza A Virus Vaccines Confer Broad Protection against Lethal Challenge
title_short	Nonreplicating Influenza A Virus Vaccines Confer Broad Protection against Lethal Challenge
title_full	Nonreplicating Influenza A Virus Vaccines Confer Broad Protection against Lethal Challenge
title_fullStr	Nonreplicating Influenza A Virus Vaccines Confer Broad Protection against Lethal Challenge
title_full_unstemmed	Nonreplicating Influenza A Virus Vaccines Confer Broad Protection against Lethal Challenge
title_sort	nonreplicating influenza a virus vaccines confer broad protection against lethal challenge
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/79a9b26e4bc64166a35f0eb2fe4f499e
work_keys_str_mv	AT marianabaz nonreplicatinginfluenzaavirusvaccinesconferbroadprotectionagainstlethalchallenge AT kobpornboonnak nonreplicatinginfluenzaavirusvaccinesconferbroadprotectionagainstlethalchallenge AT myeishapaskel nonreplicatinginfluenzaavirusvaccinesconferbroadprotectionagainstlethalchallenge AT celiasantos nonreplicatinginfluenzaavirusvaccinesconferbroadprotectionagainstlethalchallenge AT timothypowell nonreplicatinginfluenzaavirusvaccinesconferbroadprotectionagainstlethalchallenge AT alaintownsend nonreplicatinginfluenzaavirusvaccinesconferbroadprotectionagainstlethalchallenge AT kantasubbarao nonreplicatinginfluenzaavirusvaccinesconferbroadprotectionagainstlethalchallenge
_version_	1718427712768442368

Nonreplicating Influenza A Virus Vaccines Confer Broad Protection against Lethal Challenge

Ejemplares similares