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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.

Cox RJ, Major D, Pedersen G, Pathirana RD, Hoschler K, Guilfoyle K, Roseby S, Bredholt G, Assmus J, Breakwell L, Campitelli L, Sjursen H - PLoS ONE (2015)

Bottom Line: Highly pathogenic avian influenza (HPAI) viruses constitute a pandemic threat and the development of effective vaccines is a global priority.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.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.

View Article: PubMed Central - PubMed

Affiliation: Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Research and Development, Haukeland University Hospital, Bergen, Norway; Jebsen Centre for Influenza Vaccine Research, University of Bergen, Bergen, Norway.

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 30 μg HA alone or 1.5, 7.5 or 30 μg 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 pre-pandemic vaccine candidate.

Trial registration: ClinicalTrials.gov NCT00868218.

No MeSH data available.


Related in: MedlinePlus

The longevity of the haemagglutination inhibition antibody response induced after vaccination.A: The haemagglutination inhibition (HI) response against the homologous vaccine strain A/Vietnam/1194/2004 (NIBRG-14) at 180 and 365 days after vaccination. B: The cross-H5 clade HI response to A/turkey/Turkey/1/2005 (NIBRG-23), A/Indonesia/5/2005 (RG2) and A/Cambodia/R0405050/2007 (NIBRG-88) at 180 days post-vaccination. Subjects were vaccinated with two doses (21 ±1 days apart) of inactivated virosomal H5N1 vaccine alone (30μg HA, blue) or 1.5 (red), 7.5 (green) or 30 μg HA (black) adjuvanted with Matrix-M (50μg). The HI titres were measured by the modified HI test using horse erythrocytes. Each symbol represents the geometric HI titre for one individual participant, with geometric mean titres for the group and 95% confidence interval presented. The dotted line shows the protective HI titre of 32.
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pone.0131652.g005: The longevity of the haemagglutination inhibition antibody response induced after vaccination.A: The haemagglutination inhibition (HI) response against the homologous vaccine strain A/Vietnam/1194/2004 (NIBRG-14) at 180 and 365 days after vaccination. B: The cross-H5 clade HI response to A/turkey/Turkey/1/2005 (NIBRG-23), A/Indonesia/5/2005 (RG2) and A/Cambodia/R0405050/2007 (NIBRG-88) at 180 days post-vaccination. Subjects were vaccinated with two doses (21 ±1 days apart) of inactivated virosomal H5N1 vaccine alone (30μg HA, blue) or 1.5 (red), 7.5 (green) or 30 μg HA (black) adjuvanted with Matrix-M (50μg). The HI titres were measured by the modified HI test using horse erythrocytes. Each symbol represents the geometric HI titre for one individual participant, with geometric mean titres for the group and 95% confidence interval presented. The dotted line shows the protective HI titre of 32.

Mentions: Fig 5A shows the NIBRG-14-specific HI responses at days 180 and 365 post-vaccination. On day 180, the 45% of subjects in the adjuvanted 30μg HA (GMT = 23) and 29% in the 7.5μg HA (GMT = 10) groups were seroprotected, whilst in the 1.5μg HA group, two persons (21%) had a seroprotective response (GMT = 6). In the virosomal alone vaccine group, 23% of subjects had HI titres ≥32 (GMT = 8). At 12 months after vaccination, only two volunteers from the adjuvanted 30μg HA group and one from the 7.5μg HA had seroprotective HI titres. Fig 5B shows that generally no long term protective HI responses were observed against the other H5N1 strains, except four persons (across all four vaccinated groups) were seroprotected against NIBRG-88 and two against NIBRG-23 strains at 6 months post vaccination. No cross-H5 clade HI responses were observed at 12 months post-vaccination (data not shown).


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.

Cox RJ, Major D, Pedersen G, Pathirana RD, Hoschler K, Guilfoyle K, Roseby S, Bredholt G, Assmus J, Breakwell L, Campitelli L, Sjursen H - PLoS ONE (2015)

The longevity of the haemagglutination inhibition antibody response induced after vaccination.A: The haemagglutination inhibition (HI) response against the homologous vaccine strain A/Vietnam/1194/2004 (NIBRG-14) at 180 and 365 days after vaccination. B: The cross-H5 clade HI response to A/turkey/Turkey/1/2005 (NIBRG-23), A/Indonesia/5/2005 (RG2) and A/Cambodia/R0405050/2007 (NIBRG-88) at 180 days post-vaccination. Subjects were vaccinated with two doses (21 ±1 days apart) of inactivated virosomal H5N1 vaccine alone (30μg HA, blue) or 1.5 (red), 7.5 (green) or 30 μg HA (black) adjuvanted with Matrix-M (50μg). The HI titres were measured by the modified HI test using horse erythrocytes. Each symbol represents the geometric HI titre for one individual participant, with geometric mean titres for the group and 95% confidence interval presented. The dotted line shows the protective HI titre of 32.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493055&req=5

pone.0131652.g005: The longevity of the haemagglutination inhibition antibody response induced after vaccination.A: The haemagglutination inhibition (HI) response against the homologous vaccine strain A/Vietnam/1194/2004 (NIBRG-14) at 180 and 365 days after vaccination. B: The cross-H5 clade HI response to A/turkey/Turkey/1/2005 (NIBRG-23), A/Indonesia/5/2005 (RG2) and A/Cambodia/R0405050/2007 (NIBRG-88) at 180 days post-vaccination. Subjects were vaccinated with two doses (21 ±1 days apart) of inactivated virosomal H5N1 vaccine alone (30μg HA, blue) or 1.5 (red), 7.5 (green) or 30 μg HA (black) adjuvanted with Matrix-M (50μg). The HI titres were measured by the modified HI test using horse erythrocytes. Each symbol represents the geometric HI titre for one individual participant, with geometric mean titres for the group and 95% confidence interval presented. The dotted line shows the protective HI titre of 32.
Mentions: Fig 5A shows the NIBRG-14-specific HI responses at days 180 and 365 post-vaccination. On day 180, the 45% of subjects in the adjuvanted 30μg HA (GMT = 23) and 29% in the 7.5μg HA (GMT = 10) groups were seroprotected, whilst in the 1.5μg HA group, two persons (21%) had a seroprotective response (GMT = 6). In the virosomal alone vaccine group, 23% of subjects had HI titres ≥32 (GMT = 8). At 12 months after vaccination, only two volunteers from the adjuvanted 30μg HA group and one from the 7.5μg HA had seroprotective HI titres. Fig 5B shows that generally no long term protective HI responses were observed against the other H5N1 strains, except four persons (across all four vaccinated groups) were seroprotected against NIBRG-88 and two against NIBRG-23 strains at 6 months post vaccination. No cross-H5 clade HI responses were observed at 12 months post-vaccination (data not shown).

Bottom Line: Highly pathogenic avian influenza (HPAI) viruses constitute a pandemic threat and the development of effective vaccines is a global priority.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.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.

View Article: PubMed Central - PubMed

Affiliation: Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Research and Development, Haukeland University Hospital, Bergen, Norway; Jebsen Centre for Influenza Vaccine Research, University of Bergen, Bergen, Norway.

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 30 μg HA alone or 1.5, 7.5 or 30 μg 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 pre-pandemic vaccine candidate.

Trial registration: ClinicalTrials.gov NCT00868218.

No MeSH data available.


Related in: MedlinePlus