TY - JOUR T1 - M2e-displaying virus-like particles with associated RNA promote T helper 1 type adaptive immunity against influenza A. JF - PLoS One Y1 - 2013 A1 - Ibañez, Lorena Itatí A1 - Roose, Kenny A1 - De Filette, Marina A1 - Schotsaert, Michael A1 - De Sloovere, Jessica A1 - S. Roels A1 - Pollard, Charlotte A1 - Schepens, Bert A1 - Grooten, Johan A1 - Fiers, Walter A1 - Saelens, Xavier KW - Adaptive Immunity KW - Adaptor Proteins, Vesicular Transport KW - Animals KW - Female KW - Humans KW - Immunity, Cellular KW - Influenza A Virus, H3N2 Subtype KW - Influenza Vaccines KW - Influenza, Human KW - Lung KW - mice KW - Myeloid Differentiation Factor 88 KW - Orthomyxoviridae Infections KW - Rna KW - Signal Transduction KW - Th1 Cells KW - Vaccination KW - Vaccines, Virus-Like Particle KW - Viral Load AB -

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.

VL - 8 CP - 3 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23527091?dopt=Abstract M3 - 10.1371/journal.pone.0059081 ER -