A Live Probiotic Vaccine Prototype Based on Conserved Influenza a Virus Antigens Protect Mice against Lethal Influenza Virus Infection

Background: Due to the highly variable nature of the antigenic properties of the influenza virus, many efforts have been made to develop broadly reactive influenza vaccines. Various vaccine platforms have been explored to deliver conserved viral antigens to the target cells to induce cross-reactive...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Daria Mezhenskaya, Irina Isakova-Sivak, Tatiana Gupalova, Elena Bormotova, Eugenia Kuleshevich, Tatiana Kramskaya, Galina Leontieva, Larisa Rudenko, Alexander Suvorov
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Enterococcus faecium</i> L3 influenza LAH antigen M2e antigen IgG oral immunization Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1c22c69dd64a4a81b0cf39e694352bed
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1c22c69dd64a4a81b0cf39e694352bed
record_format	dspace
spelling	oai:doaj.org-article:1c22c69dd64a4a81b0cf39e694352bed2021-11-25T16:48:26ZA Live Probiotic Vaccine Prototype Based on Conserved Influenza a Virus Antigens Protect Mice against Lethal Influenza Virus Infection10.3390/biomedicines91115152227-9059https://doaj.org/article/1c22c69dd64a4a81b0cf39e694352bed2021-10-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1515https://doaj.org/toc/2227-9059Background: Due to the highly variable nature of the antigenic properties of the influenza virus, many efforts have been made to develop broadly reactive influenza vaccines. Various vaccine platforms have been explored to deliver conserved viral antigens to the target cells to induce cross-reactive immune responses. Here, we assessed the feasibility of using <i>Enterococcus faecium</i> L3 as a bacterial vector for oral immunization against influenza virus. Methods: we generated two vaccine prototypes by inserting full-length HA2 (L3-HA2) protein or its long alpha helix (LAH) domain in combination with four M2e tandem repeats (L3-LAH+M2e) into genome of <i>E.faecium</i> L3 probiotic strain. The immunogenicity and protective potential of these oral vaccines were assessed in a lethal challenge model in BALB/c mice. Results: as expected, both vaccine prototypes induced HA stem-targeting antibodies, whereas only L3-LAH+4M2e vaccine induced M2e-specific antibody. The L3-HA2 vaccine partially protected mice against lethal challenge with two H1N1 heterologous viruses, while 100% of animals in the L3-LAH+4M2e vaccine group survived in both challenge experiments, and there was significant protection against weight loss in this group, compared to the L3 vector-immunized control mice. Conclusions: the recombinant enterococcal strain L3-LAH+4M2e can be considered as a promising live probiotic vaccine candidate for influenza prevention and warrants further evaluation in relevant pre-clinical models.Daria MezhenskayaIrina Isakova-SivakTatiana GupalovaElena BormotovaEugenia KuleshevichTatiana KramskayaGalina LeontievaLarisa RudenkoAlexander SuvorovMDPI AGarticle<i>Enterococcus faecium</i> L3influenzaLAH antigenM2e antigenIgGoral immunizationBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1515, p 1515 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Enterococcus faecium</i> L3 influenza LAH antigen M2e antigen IgG oral immunization Biology (General) QH301-705.5
spellingShingle	<i>Enterococcus faecium</i> L3 influenza LAH antigen M2e antigen IgG oral immunization Biology (General) QH301-705.5 Daria Mezhenskaya Irina Isakova-Sivak Tatiana Gupalova Elena Bormotova Eugenia Kuleshevich Tatiana Kramskaya Galina Leontieva Larisa Rudenko Alexander Suvorov A Live Probiotic Vaccine Prototype Based on Conserved Influenza a Virus Antigens Protect Mice against Lethal Influenza Virus Infection
description	Background: Due to the highly variable nature of the antigenic properties of the influenza virus, many efforts have been made to develop broadly reactive influenza vaccines. Various vaccine platforms have been explored to deliver conserved viral antigens to the target cells to induce cross-reactive immune responses. Here, we assessed the feasibility of using <i>Enterococcus faecium</i> L3 as a bacterial vector for oral immunization against influenza virus. Methods: we generated two vaccine prototypes by inserting full-length HA2 (L3-HA2) protein or its long alpha helix (LAH) domain in combination with four M2e tandem repeats (L3-LAH+M2e) into genome of <i>E.faecium</i> L3 probiotic strain. The immunogenicity and protective potential of these oral vaccines were assessed in a lethal challenge model in BALB/c mice. Results: as expected, both vaccine prototypes induced HA stem-targeting antibodies, whereas only L3-LAH+4M2e vaccine induced M2e-specific antibody. The L3-HA2 vaccine partially protected mice against lethal challenge with two H1N1 heterologous viruses, while 100% of animals in the L3-LAH+4M2e vaccine group survived in both challenge experiments, and there was significant protection against weight loss in this group, compared to the L3 vector-immunized control mice. Conclusions: the recombinant enterococcal strain L3-LAH+4M2e can be considered as a promising live probiotic vaccine candidate for influenza prevention and warrants further evaluation in relevant pre-clinical models.
format	article
author	Daria Mezhenskaya Irina Isakova-Sivak Tatiana Gupalova Elena Bormotova Eugenia Kuleshevich Tatiana Kramskaya Galina Leontieva Larisa Rudenko Alexander Suvorov
author_facet	Daria Mezhenskaya Irina Isakova-Sivak Tatiana Gupalova Elena Bormotova Eugenia Kuleshevich Tatiana Kramskaya Galina Leontieva Larisa Rudenko Alexander Suvorov
author_sort	Daria Mezhenskaya
title	A Live Probiotic Vaccine Prototype Based on Conserved Influenza a Virus Antigens Protect Mice against Lethal Influenza Virus Infection
title_short	A Live Probiotic Vaccine Prototype Based on Conserved Influenza a Virus Antigens Protect Mice against Lethal Influenza Virus Infection
title_full	A Live Probiotic Vaccine Prototype Based on Conserved Influenza a Virus Antigens Protect Mice against Lethal Influenza Virus Infection
title_fullStr	A Live Probiotic Vaccine Prototype Based on Conserved Influenza a Virus Antigens Protect Mice against Lethal Influenza Virus Infection
title_full_unstemmed	A Live Probiotic Vaccine Prototype Based on Conserved Influenza a Virus Antigens Protect Mice against Lethal Influenza Virus Infection
title_sort	live probiotic vaccine prototype based on conserved influenza a virus antigens protect mice against lethal influenza virus infection
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1c22c69dd64a4a81b0cf39e694352bed
work_keys_str_mv	AT dariamezhenskaya aliveprobioticvaccineprototypebasedonconservedinfluenzaavirusantigensprotectmiceagainstlethalinfluenzavirusinfection AT irinaisakovasivak aliveprobioticvaccineprototypebasedonconservedinfluenzaavirusantigensprotectmiceagainstlethalinfluenzavirusinfection AT tatianagupalova aliveprobioticvaccineprototypebasedonconservedinfluenzaavirusantigensprotectmiceagainstlethalinfluenzavirusinfection AT elenabormotova aliveprobioticvaccineprototypebasedonconservedinfluenzaavirusantigensprotectmiceagainstlethalinfluenzavirusinfection AT eugeniakuleshevich aliveprobioticvaccineprototypebasedonconservedinfluenzaavirusantigensprotectmiceagainstlethalinfluenzavirusinfection AT tatianakramskaya aliveprobioticvaccineprototypebasedonconservedinfluenzaavirusantigensprotectmiceagainstlethalinfluenzavirusinfection AT galinaleontieva aliveprobioticvaccineprototypebasedonconservedinfluenzaavirusantigensprotectmiceagainstlethalinfluenzavirusinfection AT larisarudenko aliveprobioticvaccineprototypebasedonconservedinfluenzaavirusantigensprotectmiceagainstlethalinfluenzavirusinfection AT alexandersuvorov aliveprobioticvaccineprototypebasedonconservedinfluenzaavirusantigensprotectmiceagainstlethalinfluenzavirusinfection AT dariamezhenskaya liveprobioticvaccineprototypebasedonconservedinfluenzaavirusantigensprotectmiceagainstlethalinfluenzavirusinfection AT irinaisakovasivak liveprobioticvaccineprototypebasedonconservedinfluenzaavirusantigensprotectmiceagainstlethalinfluenzavirusinfection AT tatianagupalova liveprobioticvaccineprototypebasedonconservedinfluenzaavirusantigensprotectmiceagainstlethalinfluenzavirusinfection AT elenabormotova liveprobioticvaccineprototypebasedonconservedinfluenzaavirusantigensprotectmiceagainstlethalinfluenzavirusinfection AT eugeniakuleshevich liveprobioticvaccineprototypebasedonconservedinfluenzaavirusantigensprotectmiceagainstlethalinfluenzavirusinfection AT tatianakramskaya liveprobioticvaccineprototypebasedonconservedinfluenzaavirusantigensprotectmiceagainstlethalinfluenzavirusinfection AT galinaleontieva liveprobioticvaccineprototypebasedonconservedinfluenzaavirusantigensprotectmiceagainstlethalinfluenzavirusinfection AT larisarudenko liveprobioticvaccineprototypebasedonconservedinfluenzaavirusantigensprotectmiceagainstlethalinfluenzavirusinfection AT alexandersuvorov liveprobioticvaccineprototypebasedonconservedinfluenzaavirusantigensprotectmiceagainstlethalinfluenzavirusinfection
_version_	1718412942307753984

A Live Probiotic Vaccine Prototype Based on Conserved Influenza a Virus Antigens Protect Mice against Lethal Influenza Virus Infection

Ejemplares similares