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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 antibody secreting cell response induced after influenza vaccination.Lymphocytes were collected 7 days after the first (day 7) and second vaccine dose (day 28) of inactivated virosomal H5N1 vaccine alone or formulated 1.5, 7.5 or 30μg HA formulated with Matrix-M (50μg). The influenza-specific IgG, IgA and IgM antibody secreting cells (ASC) were enumerated using the ELISPOT assay. The data are presented as the mean number of influenza-specific ASC per 200 000 lymphocytes ± standard error of the mean to the homologous vaccine strain A/Vietnam/1104/2004 (NIBRG-14), and the heterologous responses to A/Turkey/Turkey/1/05 (NIBRG-23), A/Cambodia/R0405050/2007 (NIBRG-88) and A/Anhui/1/05 (RG6). Statistical differences between the adjuvanted and non-adjuvanted groups were calculated by ANOVA with Dunnett’s multiple comparisons test. *p<0.05.
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pone.0131652.g008: The antibody secreting cell response induced after influenza vaccination.Lymphocytes were collected 7 days after the first (day 7) and second vaccine dose (day 28) of inactivated virosomal H5N1 vaccine alone or formulated 1.5, 7.5 or 30μg HA formulated with Matrix-M (50μg). The influenza-specific IgG, IgA and IgM antibody secreting cells (ASC) were enumerated using the ELISPOT assay. The data are presented as the mean number of influenza-specific ASC per 200 000 lymphocytes ± standard error of the mean to the homologous vaccine strain A/Vietnam/1104/2004 (NIBRG-14), and the heterologous responses to A/Turkey/Turkey/1/05 (NIBRG-23), A/Cambodia/R0405050/2007 (NIBRG-88) and A/Anhui/1/05 (RG6). Statistical differences between the adjuvanted and non-adjuvanted groups were calculated by ANOVA with Dunnett’s multiple comparisons test. *p<0.05.

Mentions: No or very low NIBRG-14-specific ASCs were detected prior to vaccination (data not shown). Fig 8 shows the homologous and cross-H5 clade IgG, IgA and IgM ASC responses after the first (day 7) and second (day 28) vaccine doses. On day 7, the strongest IgG, IgA and IgM ASC responses against both the homologous and cross-reactive strains were detected in the groups that received the adjuvanted high dose (7.5 and 30μg HA) vaccines. After the second dose (day 28), the strongest ASC responses were observed in the group that received the adjuvanted 1.5μg HA vaccine and the ASC responses were dominated by IgG while very low IgA and IgM levels were detected.


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 antibody secreting cell response induced after influenza vaccination.Lymphocytes were collected 7 days after the first (day 7) and second vaccine dose (day 28) of inactivated virosomal H5N1 vaccine alone or formulated 1.5, 7.5 or 30μg HA formulated with Matrix-M (50μg). The influenza-specific IgG, IgA and IgM antibody secreting cells (ASC) were enumerated using the ELISPOT assay. The data are presented as the mean number of influenza-specific ASC per 200 000 lymphocytes ± standard error of the mean to the homologous vaccine strain A/Vietnam/1104/2004 (NIBRG-14), and the heterologous responses to A/Turkey/Turkey/1/05 (NIBRG-23), A/Cambodia/R0405050/2007 (NIBRG-88) and A/Anhui/1/05 (RG6). Statistical differences between the adjuvanted and non-adjuvanted groups were calculated by ANOVA with Dunnett’s multiple comparisons test. *p<0.05.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131652.g008: The antibody secreting cell response induced after influenza vaccination.Lymphocytes were collected 7 days after the first (day 7) and second vaccine dose (day 28) of inactivated virosomal H5N1 vaccine alone or formulated 1.5, 7.5 or 30μg HA formulated with Matrix-M (50μg). The influenza-specific IgG, IgA and IgM antibody secreting cells (ASC) were enumerated using the ELISPOT assay. The data are presented as the mean number of influenza-specific ASC per 200 000 lymphocytes ± standard error of the mean to the homologous vaccine strain A/Vietnam/1104/2004 (NIBRG-14), and the heterologous responses to A/Turkey/Turkey/1/05 (NIBRG-23), A/Cambodia/R0405050/2007 (NIBRG-88) and A/Anhui/1/05 (RG6). Statistical differences between the adjuvanted and non-adjuvanted groups were calculated by ANOVA with Dunnett’s multiple comparisons test. *p<0.05.
Mentions: No or very low NIBRG-14-specific ASCs were detected prior to vaccination (data not shown). Fig 8 shows the homologous and cross-H5 clade IgG, IgA and IgM ASC responses after the first (day 7) and second (day 28) vaccine doses. On day 7, the strongest IgG, IgA and IgM ASC responses against both the homologous and cross-reactive strains were detected in the groups that received the adjuvanted high dose (7.5 and 30μg HA) vaccines. After the second dose (day 28), the strongest ASC responses were observed in the group that received the adjuvanted 1.5μg HA vaccine and the ASC responses were dominated by IgG while very low IgA and IgM levels were detected.

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