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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

CONSORT flowchart.In total, 65 adult subjects were assessed for eligibility and 60 were included in the study (mean age 31 years old, 60% female). Prior to being enrolled in the study, all participants provided written informed consent and were screened for normal haematology, biochemistry and immunology parameters. The 60 volunteers were randomised into four groups and were immunised twice, 21 days (±1) apart with the virosomal H5N1 vaccine alone (30μg HA) or with vaccine (1.5, 7.5 or 30μg HA) formulated with Matrix-M (50μg) adjuvant. Blood samples were collected at 7, 14 and 21 days after each dose of vaccine and 180 and 365 days after the first vaccination.
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pone.0131652.g001: CONSORT flowchart.In total, 65 adult subjects were assessed for eligibility and 60 were included in the study (mean age 31 years old, 60% female). Prior to being enrolled in the study, all participants provided written informed consent and were screened for normal haematology, biochemistry and immunology parameters. The 60 volunteers were randomised into four groups and were immunised twice, 21 days (±1) apart with the virosomal H5N1 vaccine alone (30μg HA) or with vaccine (1.5, 7.5 or 30μg HA) formulated with Matrix-M (50μg) adjuvant. Blood samples were collected at 7, 14 and 21 days after each dose of vaccine and 180 and 365 days after the first vaccination.

Mentions: In this study, we investigated the early kinetics and the long-term persistence of the serological responses induced by a candidate H5N1 vaccine formulated with or without the Matrix M adjuvant. Serological responses were determined against both the homologous vaccine as well as clade 1 and 2 H5N1 strains. Fig 1 shows the CONSORT flowchart of the clinical trial and the CONSORT checklist (S1 File), N3CRs Arrive guidelines (S2 File) and study protocol (S3 File) are provided as supporting information. The protective efficacy of the vaccine formulations against challenge with HPAI virus was tested in a ferret infection model.


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)

CONSORT flowchart.In total, 65 adult subjects were assessed for eligibility and 60 were included in the study (mean age 31 years old, 60% female). Prior to being enrolled in the study, all participants provided written informed consent and were screened for normal haematology, biochemistry and immunology parameters. The 60 volunteers were randomised into four groups and were immunised twice, 21 days (±1) apart with the virosomal H5N1 vaccine alone (30μg HA) or with vaccine (1.5, 7.5 or 30μg HA) formulated with Matrix-M (50μg) adjuvant. Blood samples were collected at 7, 14 and 21 days after each dose of vaccine and 180 and 365 days after the first vaccination.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131652.g001: CONSORT flowchart.In total, 65 adult subjects were assessed for eligibility and 60 were included in the study (mean age 31 years old, 60% female). Prior to being enrolled in the study, all participants provided written informed consent and were screened for normal haematology, biochemistry and immunology parameters. The 60 volunteers were randomised into four groups and were immunised twice, 21 days (±1) apart with the virosomal H5N1 vaccine alone (30μg HA) or with vaccine (1.5, 7.5 or 30μg HA) formulated with Matrix-M (50μg) adjuvant. Blood samples were collected at 7, 14 and 21 days after each dose of vaccine and 180 and 365 days after the first vaccination.
Mentions: In this study, we investigated the early kinetics and the long-term persistence of the serological responses induced by a candidate H5N1 vaccine formulated with or without the Matrix M adjuvant. Serological responses were determined against both the homologous vaccine as well as clade 1 and 2 H5N1 strains. Fig 1 shows the CONSORT flowchart of the clinical trial and the CONSORT checklist (S1 File), N3CRs Arrive guidelines (S2 File) and study protocol (S3 File) are provided as supporting information. The protective efficacy of the vaccine formulations against challenge with HPAI virus was tested in a ferret infection model.

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