tetano
Editor, Senior Moderator
PLoS One. 2015 Jul 6;10(7):e0131652. doi: 10.1371/journal.pone.0131652. eCollection 2015.
[h=1]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.[/h] Cox RJ[SUP]1[/SUP], Major D[SUP]2[/SUP], Pedersen G[SUP]3[/SUP], Pathirana RD[SUP]1[/SUP], Hoschler K[SUP]4[/SUP], Guilfoyle K[SUP]2[/SUP], Roseby S[SUP]2[/SUP], Bredholt G[SUP]1[/SUP], Assmus J[SUP]5[/SUP], Breakwell L[SUP]4[/SUP], Campitelli L[SUP]6[/SUP], Sjursen H[SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND AND METHODS:[/h] 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.
[h=4]RESULTS:[/h] 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.
[h=4]CONCLUSION:[/h] Our findings show that the Matrix M-adjuvanted virosomal H5N1 vaccine is a promising pre-pandemic vaccine candidate.
[h=4]TRIAL REGISTRATION:[/h] ClinicalTrials.gov NCT00868218.
PMID: 26147369 [PubMed - in process]
[h=1]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.[/h] Cox RJ[SUP]1[/SUP], Major D[SUP]2[/SUP], Pedersen G[SUP]3[/SUP], Pathirana RD[SUP]1[/SUP], Hoschler K[SUP]4[/SUP], Guilfoyle K[SUP]2[/SUP], Roseby S[SUP]2[/SUP], Bredholt G[SUP]1[/SUP], Assmus J[SUP]5[/SUP], Breakwell L[SUP]4[/SUP], Campitelli L[SUP]6[/SUP], Sjursen H[SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND AND METHODS:[/h] 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.
[h=4]RESULTS:[/h] 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.
[h=4]CONCLUSION:[/h] Our findings show that the Matrix M-adjuvanted virosomal H5N1 vaccine is a promising pre-pandemic vaccine candidate.
[h=4]TRIAL REGISTRATION:[/h] ClinicalTrials.gov NCT00868218.
PMID: 26147369 [PubMed - in process]