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Enhancing the cross protective efficacy of live attenuated influenza virus vaccine by supplemented vaccination with M2 ectodomain virus-like particles.

ABSTRACT: Current influenza vaccines including live attenuated influenza virus (LAIV) provide suboptimal protection against drift and potential pandemic strains. We hypothesized that supplementing LAIV with a highly conserved antigenic target M2 ectodomain (M2e) would confer cross-protection by inducing humoral and cellular immune responses to conserved antigenic targets. Intranasal vaccination with LAIV (A/Netherlands/602/09, H1N1) supplemented with tandem repeat M2e containing virus-like particles (M2e5x VLP) induced M2e- and virus-specific antibodies. Upon heterosubtypic virus challenge, M2e5x VLP-supplemented LAIV vaccination of mice induced significantly improved cross protection by preventing weight loss and lowering lung viral titers. Further mechanistic studies on heterosubtypic immunity suggest that T cell responses to M2e and nucleoprotein as well as systemic and mucosal antibodies to M2e and viruses might be contributing to cross protection. Therefore, this study demonstrates a novel vaccination strategy to improve the cross protective efficacy of LAIV by supplementing with a conserved M2e antigenic target.

SUBMITTER: Lee YT

PROVIDER: S-EPMC6382595 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Enhancing the cross protective efficacy of live attenuated influenza virus vaccine by supplemented vaccination with M2 ectodomain virus-like particles.

Lee Young-Tae YT Kim Ki-Hye KH Ko Eun-Ju EJ Kim Min-Chul MC Lee Yu-Na YN Hwang Hye-Suk HS Lee Youri Y Jung Yu-Jin YJ Kim Yu Jin YJ Santos Jefferson J Perez Daniel R DR Kang Sang-Moo SM

Virology 20190115

Current influenza vaccines including live attenuated influenza virus (LAIV) provide suboptimal protection against drift and potential pandemic strains. We hypothesized that supplementing LAIV with a highly conserved antigenic target M2 ectodomain (M2e) would confer cross-protection by inducing humoral and cellular immune responses to conserved antigenic targets. Intranasal vaccination with LAIV (A/Netherlands/602/09, H1N1) supplemented with tandem repeat M2e containing virus-like particles (M2e5 ...[more]

PMID: 30685658

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Project description:African swine fever is a highly contagious viral disease of mandatory declaration to the World Organization for Animal Health (OIE). The lack of available vaccines makes its control difficult; thus, African swine fever virus (ASFV) represents a major threat to the swine industry. Inactivated vaccines do not confer solid protection against ASFV. Conversely, live attenuated viruses (LAV), either naturally isolated or obtained by genetic manipulation, have demonstrated reliable protection against homologous ASFV strains, although little or no protection has been demonstrated against heterologous viruses. Safety concerns are a major issue for the use of ASFV attenuated vaccine candidates and have hampered their implementation in the field so far. While trying to develop safer and efficient ASFV vaccines, we found that the deletion of the viral CD2v (EP402R) gene highly attenuated the virulent BA71 strain in vivo Inoculation of pigs with the deletion mutant virus BA71?CD2 conferred protection not only against lethal challenge with the parental BA71 but also against the heterologous E75 (both genotype I strains). The protection induced was dose dependent, and the cross-protection observed in vivo correlated with the ability of BA71?CD2 to induce specific CD8+ T cells capable of recognizing both BA71 and E75 viruses in vitro Interestingly, 100% of the pigs immunized with BA71?CD2 also survived lethal challenge with Georgia 2007/1, the genotype II strain of ASFV currently circulating in continental Europe. These results open new avenues to design ASFV cross-protective vaccines, essential to fight ASFV in areas where the virus is endemic and where multiple viruses are circulating.IMPORTANCE African swine fever virus (ASFV) remains enzootic in most countries of Sub-Saharan Africa, today representing a major threat for the development of their swine industry. The uncontrolled presence of ASFV has favored its periodic exportation to other countries, the last event being in Georgia in 2007. Since then, ASFV has spread toward neighboring countries, reaching the European Union's east border in 2014. The lack of available vaccines against ASFV makes its control difficult; so far, only live attenuated viruses have demonstrated solid protection against homologous experimental challenges, but they have failed at inducing solid cross-protective immunity against heterologous viruses. Here we describe a new LAV candidate with unique cross-protective abilities: BA71?CD2. Inoculation of BA71?CD2 protected pigs not only against experimental challenge with BA71, the virulent parental strain, but also against heterologous viruses, including Georgia 2007/1, the genotype II strain of ASFV currently circulating in Eastern Europe.

Project description:Background and aimThe majority of seasonal influenza vaccines are trivalent, containing two A virus strains (H1N1 and H3N2) and one B virus strain. The co-circulation of two distinct lineages of B viruses can lead to mismatch between the influenza B virus strain recommended for the trivalent seasonal vaccine and the circulating B virus. This has led some manufacturers to produce quadrivalent influenza vaccines containing one strain from each B lineage in addition to H1N1 and H3N2 strains. However, it is also important to know whether vaccines containing a single influenza B strain can provide cross-protectivity against viruses of the antigenically distinct lineage. The aim of this study was to assess in naïve ferrets the potential cross-protective activity of trivalent live attenuated influenza vaccine (T-LAIV) against challenge with a heterologous wild-type influenza B virus belonging to the genetically different lineage and to compare this activity with effectiveness of quadrivalent LAIV (Q-LAIV) in the ferret model.Methods and resultsFerrets were vaccinated with either one dose of trivalent LAIV containing B/Victoria or B/Yamagata lineage virus, or quadrivalent LAIV (containing both B lineages), or placebo. They were then challenged with B/Victoria or B/Yamagata lineage wild-type virus 28 days after vaccination. The ferrets were monitored for clinical signs and morbidity. Nasal swabs and lung tissue samples were analyzed for the presence of challenge virus. Antibody response to vaccination was assessed by routine hemagglutination inhibition assay. All LAIVs tested were found to be safe and effective against wild-type influenza B viruses based on clinical signs, and virological and histological data. The absence of interference between vaccine strains in trivalent and quadrivalent vaccine formulations was confirmed. Trivalent LAIVs were shown to have the potential to be cross-protective against infection with genetically different influenza B/Victoria and B/Yamagata lineages.ConclusionsIn this ferret model, quadrivalent vaccine provided higher protection to challenge against both B/Victoria and B/Yamagata lineage viruses. However, T-LAIV provided some cross-protection in the case of a mismatch between circulating and vaccine type B strains. Notably, B/Victoria-based T-LAIV was more protective compared to B/Yamagata-based T-LAIV.

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Enhancing the cross protective efficacy of live attenuated influenza virus vaccine by supplemented vaccination with M2 ectodomain virus-like particles.

Publications

Enhancing the cross protective efficacy of live attenuated influenza virus vaccine by supplemented vaccination with M2 ectodomain virus-like particles.

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