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Vaccine2018; 36(12); 1592-1598; doi: 10.1016/j.vaccine.2018.02.019

Genetic and subunit vaccines based on the stem domain of the equine influenza hemagglutinin provide homosubtypic protection against heterologous strains.

Abstract: H3N8 influenza virus strains have been associated with infectious disease in equine populations throughout the world. Although current vaccines for equine influenza stimulate a protective humoral immune response against the surface glycoproteins, disease in vaccinated horses has been frequently reported, probably due to poor induction of cross-reactive antibodies against non-matching strains. This work describes the performance of a recombinant protein vaccine expressed in prokaryotic cells (ΔHAp) and of a genetic vaccine (ΔHAe), both based on the conserved stem region of influenza hemagglutinin (HA) derived from A/equine/Argentina/1/93 (H3N8) virus. Sera from mice inoculated with these immunogens in different combinations and regimes presented reactivity in vitro against highly divergent influenza virus strains belonging to phylogenetic groups 1 and 2 (H1 and H3 subtypes, respectively), and conferred robust protection against a lethal challenge with both the homologous equine strain (100%) and the homosubtypic human strain A/Victoria/3/75 (H3N2) (70-100%). Animals vaccinated with the same antigens but challenged with the human strain A/PR/8/34 (H1N1), belonging to the phylogenetic group 1, were not protected (0-33%). Combination of protein and DNA immunogens showed higher reactivity to non-homologous strains than protein alone, although all vaccines were permissive for lung infection.
Publication Date: 2018-02-15 PubMed ID: 29454522DOI: 10.1016/j.vaccine.2018.02.019Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The study investigates the effectiveness of new genetic and subunit influenza virus vaccines made from recombinant proteins, aimed at increasing the immunogenic response to heterologous strains of equine influenza.

Research Context

  • Equine influenza, caused by H3N8 strains of the influenza virus, is a global issue that affects horse populations.
  • While current vaccines trigger a humoral immune response, they have shown poor effectiveness against different, non-matching strains.

Research Focus

  • The researchers have developed a novel recombinant protein vaccine (ΔHAp) and a genetic vaccine (ΔHAe), focusing on the conserved stem region of the influenza virus’ hemagglutinin (HA), which is responsible for virus infection in host cells.
  • The H3N8 virus is the source of these vaccines’ HA stems.

Research Methodology

  • The team administered the developed immunogens to mice in unique combinations and regimes.
  • The mice’s serum was analyzed for reactivity against numerous, vastly divergent strains of the influenza virus, part of either phylogenetic group 1 (H1 subtype) or group 2 (H3 subtype).

Key Findings

  • The vaccines provided strong 100% protection against the matching equine strain and 70-100% protection against the homosubtypic human strain A/Victoria/3/75 (H3N2).
  • However, animals vaccinated with the same vaccines but exposed to the human strain A/PR/8/34 (H1N1), from phylogenetic group 1, did not show significant protection (0-33%).
  • A combination of protein and DNA immunogens showed higher reactivity against non-matching strains compared to protein alone though all vaccines allowed for lung infection.

Research Implications

  • This study’s findings demonstrate that the newly developed vaccines could provide a more significant immune response against various equine influenza virus strains, potentially overcoming the limited effectiveness of existing vaccines that are poorly inducing of cross-reactive antibodies.
  • Despite these promising results, it is worth noting that the vaccines were unable to significantly protect against all strains, indicating room for further improvements and research.

Cite This Article

APA
Ibañez LI, Caldevilla CA, Paredes Rojas Y, Mattion N. (2018). Genetic and subunit vaccines based on the stem domain of the equine influenza hemagglutinin provide homosubtypic protection against heterologous strains. Vaccine, 36(12), 1592-1598. https://doi.org/10.1016/j.vaccine.2018.02.019

Publication

ISSN: 1873-2518
NlmUniqueID: 8406899
Country: Netherlands
Language: English
Volume: 36
Issue: 12
Pages: 1592-1598
PII: S0264-410X(18)30193-2

Researcher Affiliations

Ibañez, Lorena Itatí
  • Centro de Virología Animal (CEVAN), Instituto de Ciencia y Tecnología Dr. César Milstein, CONICET, Saladillo 2468, C1440FFX Ciudad de Buenos Aires, Argentina. Electronic address: loreitati@gmail.com.
Caldevilla, Cecilia Andrea
  • Centro de Virología Animal (CEVAN), Instituto de Ciencia y Tecnología Dr. César Milstein, CONICET, Saladillo 2468, C1440FFX Ciudad de Buenos Aires, Argentina. Electronic address: ccaldevilla@yahoo.com.ar.
Paredes Rojas, Yesica
  • Centro de Virología Animal (CEVAN), Instituto de Ciencia y Tecnología Dr. César Milstein, CONICET, Saladillo 2468, C1440FFX Ciudad de Buenos Aires, Argentina. Electronic address: yesica_lpr@hotmail.com.
Mattion, Nora
  • Centro de Virología Animal (CEVAN), Instituto de Ciencia y Tecnología Dr. César Milstein, CONICET, Saladillo 2468, C1440FFX Ciudad de Buenos Aires, Argentina. Electronic address: nmattioncevan@centromilstein.org.ar.

MeSH Terms

  • Animals
  • Cell Line
  • Cross Protection / immunology
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Horse Diseases / immunology
  • Horse Diseases / prevention & control
  • Horse Diseases / virology
  • Horses
  • Humans
  • Immunization
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza A Virus, H3N8 Subtype / immunology
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology
  • Orthomyxoviridae Infections / veterinary
  • Recombinant Proteins
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology

Citations

This article has been cited 4 times.
  1. McMillan CLD, Young PR, Watterson D, Chappell KJ. The Next Generation of Influenza Vaccines: Towards a Universal Solution. Vaccines (Basel) 2021 Jan 7;9(1).
    doi: 10.3390/vaccines9010026pubmed: 33430278google scholar: lookup
  2. Singh RK, Dhama K, Karthik K, Khandia R, Munjal A, Khurana SK, Chakraborty S, Malik YS, Virmani N, Singh R, Tripathi BN, Munir M, van der Kolk JH. A Comprehensive Review on Equine Influenza Virus: Etiology, Epidemiology, Pathobiology, Advances in Developing Diagnostics, Vaccines, and Control Strategies. Front Microbiol 2018;9:1941.
    doi: 10.3389/fmicb.2018.01941pubmed: 30237788google scholar: lookup
  3. Vilaboa N, Bloom DC, Canty W, Voellmy R. A Broad Influenza Vaccine Based on a Heat-Activated, Tissue-Restricted Replication-Competent Herpesvirus. Vaccines (Basel) 2024 Jun 23;12(7).
    doi: 10.3390/vaccines12070703pubmed: 39066341google scholar: lookup
  4. Bloom DC, Lilly C, Canty W, Vilaboa N, Voellmy R. Very Broadly Effective Hemagglutinin-Directed Influenza Vaccines with Anti-Herpetic Activity. Vaccines (Basel) 2024 May 14;12(5).
    doi: 10.3390/vaccines12050537pubmed: 38793788google scholar: lookup