Matrix M H5N1 vaccine induces cross-H5 clade humoral immune responses in a randomized clinical trial and provides protection from highly pathogenic influenza challenge in ferrets

Rebecca J. Cox, Diane Major, Gabriel Pedersen, Rishi D. Pathirana, Katja Hoschler, Kate Guilfoyle, Sarah Roseby, Geir Bredholt, Jörg Assmus, Lucy Breakwell, Laura Campitelli, Haakon Sjursen

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11 Citations (Scopus)

Abstract

Background and Methods Highly pathogenic avian influenza (HPAI) viruses constitute a pandemic threat and the development of effective vaccines is a global priority. Sixty adults were recruited into a randomized clinical trial and were intramuscularly immunized with two virosomal vaccine H5N1 (NIBRG-14) doses (21 days apart) of 30μg HA alone or 1.5, 7.5 or 30μg HA adjuvanted with Matrix M. The kinetics and longevity of the serological responses against NIBRG-14 were determined by haemagglutination inhibition (HI), single radial haemolysis (SRH), microneutralization (MN) and ELISA assays. The cross-H5 clade responses in sera were determined by HI and the antibody-secreting (ASC) cell ELISPOT assays. The protective efficacy of the vaccine against homologous HPAI challenge was evaluated in ferrets. Results The serological responses against the homologous and cross-reactive strains generally peaked one week after the second dose, and formulation with Matrix M augmented the responses. The NIBRG-14-specific seroprotection rates fell significantly by six months and were low against cross-reactive strains although the adjuvant appeared to prolong the longevity of the protective responses in some subjects. By 12 months post-vaccination, nearly all vaccinees had NIBRG-14-specific antibody titres below the protective thresholds. The Matrix M adjuvant was shown to greatly improve ASC and serum IgG responses following vaccination. In a HPAI ferret challenge model, the vaccine protected the animals from febrile responses, severe weight loss and local and systemic spread of the virus. Conclusion Our findings show that the Matrix M-adjuvanted virosomal H5N1 vaccine is a promising prepandemic vaccine candidate.

Original languageEnglish
Article numbere0131652
JournalPLoS ONE
Volume10
Issue number7
DOIs
Publication statusPublished - 6 Jul 2015

Bibliographical note

Publisher Copyright:
© 2015 Cox et al.

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