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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

Protective efficacy of the H5N1 vaccine in ferrets.Ferrets were divided into five groups of 10 and were vaccinated intramuscularly with two doses (14 days apart) of virosomal vaccine alone (30μg HA, blue) or 1.5 (red), 7.5 (green) and 30μg HA (black) adjuvanted with Matrix M (50μg). Control ferrets (brown) received PBS. Fourteen days after the second immunization, ferrets were challenged by administering A/Vietnam/1203/2004 live virus (106 EID50 in 0.4 mL PBS/BSA). (A) The serum HI antibody response 12 days after each vaccination with NIBRG-14 virosomal vaccine and fourteen days following challenge with A/Vietnam/1203/2004 virus. (B) The virus titres in the nasal washing and tissue samples after challenge with the A/Vietnam/1203/2004 virus. The limit of detection in TCID50 assay for the ferret tissue samples was 101.63TCID50/ml of homogenate. (C) The changes in weight and (D) temperature after challenge with A/Vietnam/1203/2004 live virus.
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pone.0131652.g010: Protective efficacy of the H5N1 vaccine in ferrets.Ferrets were divided into five groups of 10 and were vaccinated intramuscularly with two doses (14 days apart) of virosomal vaccine alone (30μg HA, blue) or 1.5 (red), 7.5 (green) and 30μg HA (black) adjuvanted with Matrix M (50μg). Control ferrets (brown) received PBS. Fourteen days after the second immunization, ferrets were challenged by administering A/Vietnam/1203/2004 live virus (106 EID50 in 0.4 mL PBS/BSA). (A) The serum HI antibody response 12 days after each vaccination with NIBRG-14 virosomal vaccine and fourteen days following challenge with A/Vietnam/1203/2004 virus. (B) The virus titres in the nasal washing and tissue samples after challenge with the A/Vietnam/1203/2004 virus. The limit of detection in TCID50 assay for the ferret tissue samples was 101.63TCID50/ml of homogenate. (C) The changes in weight and (D) temperature after challenge with A/Vietnam/1203/2004 live virus.

Mentions: Following the first vaccination, HI titres ≥40 were detected in one animal each from the adjuvanted 7.5 and 30μg HA groups (Fig 10A). After the second dose, the majority of ferrets (70–90%) in the adjuvanted vaccine groups had HI titres ≥40, whilst no HI responses were observed in the unadjuvanted vaccine or control groups. After the virus challenge, 80–100% of animals in the adjuvanted vaccine and 60% in the unadjuvanted vaccine groups had HI titres above the protective threshold.


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)

Protective efficacy of the H5N1 vaccine in ferrets.Ferrets were divided into five groups of 10 and were vaccinated intramuscularly with two doses (14 days apart) of virosomal vaccine alone (30μg HA, blue) or 1.5 (red), 7.5 (green) and 30μg HA (black) adjuvanted with Matrix M (50μg). Control ferrets (brown) received PBS. Fourteen days after the second immunization, ferrets were challenged by administering A/Vietnam/1203/2004 live virus (106 EID50 in 0.4 mL PBS/BSA). (A) The serum HI antibody response 12 days after each vaccination with NIBRG-14 virosomal vaccine and fourteen days following challenge with A/Vietnam/1203/2004 virus. (B) The virus titres in the nasal washing and tissue samples after challenge with the A/Vietnam/1203/2004 virus. The limit of detection in TCID50 assay for the ferret tissue samples was 101.63TCID50/ml of homogenate. (C) The changes in weight and (D) temperature after challenge with A/Vietnam/1203/2004 live virus.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4493055&req=5

pone.0131652.g010: Protective efficacy of the H5N1 vaccine in ferrets.Ferrets were divided into five groups of 10 and were vaccinated intramuscularly with two doses (14 days apart) of virosomal vaccine alone (30μg HA, blue) or 1.5 (red), 7.5 (green) and 30μg HA (black) adjuvanted with Matrix M (50μg). Control ferrets (brown) received PBS. Fourteen days after the second immunization, ferrets were challenged by administering A/Vietnam/1203/2004 live virus (106 EID50 in 0.4 mL PBS/BSA). (A) The serum HI antibody response 12 days after each vaccination with NIBRG-14 virosomal vaccine and fourteen days following challenge with A/Vietnam/1203/2004 virus. (B) The virus titres in the nasal washing and tissue samples after challenge with the A/Vietnam/1203/2004 virus. The limit of detection in TCID50 assay for the ferret tissue samples was 101.63TCID50/ml of homogenate. (C) The changes in weight and (D) temperature after challenge with A/Vietnam/1203/2004 live virus.
Mentions: Following the first vaccination, HI titres ≥40 were detected in one animal each from the adjuvanted 7.5 and 30μg HA groups (Fig 10A). After the second dose, the majority of ferrets (70–90%) in the adjuvanted vaccine groups had HI titres ≥40, whilst no HI responses were observed in the unadjuvanted vaccine or control groups. After the virus challenge, 80–100% of animals in the adjuvanted vaccine and 60% in the unadjuvanted vaccine groups had HI titres above the protective threshold.

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