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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...

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Autores principales: Mezhenskaya, Daria, Isakova-Sivak, Irina, Gupalova, Tatiana, Bormotova, Elena, Kuleshevich, Eugenia, Kramskaya, Tatiana, Leontieva, Galina, Rudenko, Larisa, Suvorov, Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615285/
https://www.ncbi.nlm.nih.gov/pubmed/34829744
http://dx.doi.org/10.3390/biomedicines9111515
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author Mezhenskaya, Daria
Isakova-Sivak, Irina
Gupalova, Tatiana
Bormotova, Elena
Kuleshevich, Eugenia
Kramskaya, Tatiana
Leontieva, Galina
Rudenko, Larisa
Suvorov, Alexander
author_facet Mezhenskaya, Daria
Isakova-Sivak, Irina
Gupalova, Tatiana
Bormotova, Elena
Kuleshevich, Eugenia
Kramskaya, Tatiana
Leontieva, Galina
Rudenko, Larisa
Suvorov, Alexander
author_sort Mezhenskaya, Daria
collection PubMed
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 Enterococcus faecium 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 E.faecium 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.
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spelling pubmed-86152852021-11-26 A Live Probiotic Vaccine Prototype Based on Conserved Influenza a Virus Antigens Protect Mice against Lethal Influenza Virus Infection Mezhenskaya, Daria Isakova-Sivak, Irina Gupalova, Tatiana Bormotova, Elena Kuleshevich, Eugenia Kramskaya, Tatiana Leontieva, Galina Rudenko, Larisa Suvorov, Alexander Biomedicines Article 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 Enterococcus faecium 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 E.faecium 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. MDPI 2021-10-21 /pmc/articles/PMC8615285/ /pubmed/34829744 http://dx.doi.org/10.3390/biomedicines9111515 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mezhenskaya, Daria
Isakova-Sivak, Irina
Gupalova, Tatiana
Bormotova, Elena
Kuleshevich, Eugenia
Kramskaya, Tatiana
Leontieva, Galina
Rudenko, Larisa
Suvorov, Alexander
A Live Probiotic Vaccine Prototype Based on Conserved Influenza a Virus Antigens Protect Mice against Lethal Influenza Virus Infection
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615285/
https://www.ncbi.nlm.nih.gov/pubmed/34829744
http://dx.doi.org/10.3390/biomedicines9111515
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