M2e-displaying virus-like particles with associated RNA promote T helper 1 type adaptive immunity against influenza A

L.I. Ibañez, K. Roose, M. De Filette, M. Schotsaert, J. De Sloovere, S. Roels, C. Pollard, B. Schepens, J. Grooten, W. Fiers, X. Saelens

Research output: Contribution to journalA1: Web of Science-article

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Abstract

The ectodomain of influenza A matrix protein 2 (M2e) is a candidate for a universal influenza A vaccine. We used recombinant Hepatitis B core antigen to produce virus-like particles presenting M2e (M2e-VLPs). We produced the VLPs with and without entrapped nucleic acids and compared their immunogenicity and protective efficacy. Immunization of BALB/c mice with M2e-VLPs containing nucleic acids induced a stronger, Th1-biased antibody response compared to particles lacking nucleic acids. The former also induced a stronger M2e-specific CD4(+) T cell response, as determined by ELISPOT. Mice vaccinated with alum-adjuvanted M2e-VLPs containing the nucleic acid-binding domain were better protected against influenza A virus challenge than mice vaccinated with similar particles lacking this domain, as deduced from the loss in body weight following challenge with X47 (H3N2) or PR/8 virus. Challenge of mice that had been immunized with M2e-VLPs with or without nucleic acids displayed significantly lower mortality, morbidity and lung virus titers than control-immunized groups. We conclude that nucleic acids present in M2e-VLPs correlate with improved immune protection.
Original languageEnglish
JournalPLoS ONE
Volume8
Issue number3
Pages (from-to)e59081
ISSN1932-6203
DOIs
Publication statusPublished - 2013

Keywords

  • Viral diseases
  • Influenza
  • Research
  • Vaccine development
  • Immune response
  • Proteins
  • Nucleic acids
  • Immunogenicity
  • Efficacy
  • Vaccination
  • Antibodies
  • CD4-positive-T-lymphocytes
  • In vivo
  • Mice
  • Laboratory techniques and procedures

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