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Matrix-M Adjuvated Seasonal Virosomal Influenza Vaccine Induces Partial Protection in Mice and Ferrets against Avian H5 and H7 Challenge.

Cox F, Roos A, Hafkemeijer N, Baart M, Tolboom J, Dekking L, Stittelaar K, Goudsmit J, Radošević K, Saeland E - PLoS ONE (2015)

Bottom Line: An effective pre-pandemic vaccine is therefore required as a first line of defense.In contrast, reduced upper and lower respiratory tract viral loads and reduced lung pathology, was achieved in H5N1 challenged ferrets.Together these results suggest that, at least to some extent, Matrix-M adjuvated seasonal virosomal influenza vaccine can serve as an interim measure to decrease morbidity and mortality associated with a pandemic outbreak.

View Article: PubMed Central - PubMed

Affiliation: Janssen Prevention Center, Center of Excellence of Janssen Research & Development, Pharmaceutical companies of Johnson and Johnson, Leiden, The Netherlands.

ABSTRACT
There is a constant threat of zoonotic influenza viruses causing a pandemic outbreak in humans. It is virtually impossible to predict which virus strain will cause the next pandemic and it takes a considerable amount of time before a safe and effective vaccine will be available once a pandemic occurs. In addition, development of pandemic vaccines is hampered by the generally poor immunogenicity of avian influenza viruses in humans. An effective pre-pandemic vaccine is therefore required as a first line of defense. Broadening of the protective efficacy of current seasonal vaccines by adding an adjuvant may be a way to provide such first line of defense. Here we evaluate whether a seasonal trivalent virosomal vaccine (TVV) adjuvated with the saponin-based adjuvant Matrix-M (MM) can confer protection against avian influenza H5 and H7 virus strains in mice and ferrets. We demonstrate that mice were protected from death against challenges with H5N1 and H7N7, but that the protection was not complete as evidenced by severe clinical signs. In ferrets, protection against H7N9 was not observed. In contrast, reduced upper and lower respiratory tract viral loads and reduced lung pathology, was achieved in H5N1 challenged ferrets. Together these results suggest that, at least to some extent, Matrix-M adjuvated seasonal virosomal influenza vaccine can serve as an interim measure to decrease morbidity and mortality associated with a pandemic outbreak.

No MeSH data available.


Related in: MedlinePlus

TVV+MM protects mice against avian H7N7.Mice (n = 10/group) were immunized 1x or 2x with TVV with or without MM. Four weeks later, mice were challenged with 25xLD50 H7N7 A/Chicken/Netherlands/62155710/03 and monitored for 21 days for survival, body weight loss and clinical symptoms. Graphs represent the Kaplan-Meier survival curve (A and D) or mean bodyweight change with 95% confidence interval (B and E) or mean clinical scores with interquartile range (C and F). Asterisks indicate statistically significant differences compared to the vehicle control group (*p<0.05, **p<0.01, ***p<0.001, according to the materials and methods section).
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pone.0135723.g003: TVV+MM protects mice against avian H7N7.Mice (n = 10/group) were immunized 1x or 2x with TVV with or without MM. Four weeks later, mice were challenged with 25xLD50 H7N7 A/Chicken/Netherlands/62155710/03 and monitored for 21 days for survival, body weight loss and clinical symptoms. Graphs represent the Kaplan-Meier survival curve (A and D) or mean bodyweight change with 95% confidence interval (B and E) or mean clinical scores with interquartile range (C and F). Asterisks indicate statistically significant differences compared to the vehicle control group (*p<0.05, **p<0.01, ***p<0.001, according to the materials and methods section).

Mentions: Next, we assessed whether TVV+MM was able to induce protective immunity against influenza virus H7N7. One or two immunizations with TVV or a single immunization with TVV+MM did not protect mice against death after H7N7 challenge (Fig 3A). However, two immunizations with TVV+MM resulted in 60% survival, reaching statistical significance compared to the vehicle control (p = 0.022) (Fig 3D). Comparable with the H5N1 results, protection against H7N7 was accompanied by substantial body weight loss and serious clinical signs (Fig 3E and 3F). While mice that received two immunizations with TVV+MM showed significantly reduced clinical signs (p<0.001), the body weight change did not significantly differ from the vehicle control group (Fig 3E and 3F).


Matrix-M Adjuvated Seasonal Virosomal Influenza Vaccine Induces Partial Protection in Mice and Ferrets against Avian H5 and H7 Challenge.

Cox F, Roos A, Hafkemeijer N, Baart M, Tolboom J, Dekking L, Stittelaar K, Goudsmit J, Radošević K, Saeland E - PLoS ONE (2015)

TVV+MM protects mice against avian H7N7.Mice (n = 10/group) were immunized 1x or 2x with TVV with or without MM. Four weeks later, mice were challenged with 25xLD50 H7N7 A/Chicken/Netherlands/62155710/03 and monitored for 21 days for survival, body weight loss and clinical symptoms. Graphs represent the Kaplan-Meier survival curve (A and D) or mean bodyweight change with 95% confidence interval (B and E) or mean clinical scores with interquartile range (C and F). Asterisks indicate statistically significant differences compared to the vehicle control group (*p<0.05, **p<0.01, ***p<0.001, according to the materials and methods section).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581625&req=5

pone.0135723.g003: TVV+MM protects mice against avian H7N7.Mice (n = 10/group) were immunized 1x or 2x with TVV with or without MM. Four weeks later, mice were challenged with 25xLD50 H7N7 A/Chicken/Netherlands/62155710/03 and monitored for 21 days for survival, body weight loss and clinical symptoms. Graphs represent the Kaplan-Meier survival curve (A and D) or mean bodyweight change with 95% confidence interval (B and E) or mean clinical scores with interquartile range (C and F). Asterisks indicate statistically significant differences compared to the vehicle control group (*p<0.05, **p<0.01, ***p<0.001, according to the materials and methods section).
Mentions: Next, we assessed whether TVV+MM was able to induce protective immunity against influenza virus H7N7. One or two immunizations with TVV or a single immunization with TVV+MM did not protect mice against death after H7N7 challenge (Fig 3A). However, two immunizations with TVV+MM resulted in 60% survival, reaching statistical significance compared to the vehicle control (p = 0.022) (Fig 3D). Comparable with the H5N1 results, protection against H7N7 was accompanied by substantial body weight loss and serious clinical signs (Fig 3E and 3F). While mice that received two immunizations with TVV+MM showed significantly reduced clinical signs (p<0.001), the body weight change did not significantly differ from the vehicle control group (Fig 3E and 3F).

Bottom Line: An effective pre-pandemic vaccine is therefore required as a first line of defense.In contrast, reduced upper and lower respiratory tract viral loads and reduced lung pathology, was achieved in H5N1 challenged ferrets.Together these results suggest that, at least to some extent, Matrix-M adjuvated seasonal virosomal influenza vaccine can serve as an interim measure to decrease morbidity and mortality associated with a pandemic outbreak.

View Article: PubMed Central - PubMed

Affiliation: Janssen Prevention Center, Center of Excellence of Janssen Research & Development, Pharmaceutical companies of Johnson and Johnson, Leiden, The Netherlands.

ABSTRACT
There is a constant threat of zoonotic influenza viruses causing a pandemic outbreak in humans. It is virtually impossible to predict which virus strain will cause the next pandemic and it takes a considerable amount of time before a safe and effective vaccine will be available once a pandemic occurs. In addition, development of pandemic vaccines is hampered by the generally poor immunogenicity of avian influenza viruses in humans. An effective pre-pandemic vaccine is therefore required as a first line of defense. Broadening of the protective efficacy of current seasonal vaccines by adding an adjuvant may be a way to provide such first line of defense. Here we evaluate whether a seasonal trivalent virosomal vaccine (TVV) adjuvated with the saponin-based adjuvant Matrix-M (MM) can confer protection against avian influenza H5 and H7 virus strains in mice and ferrets. We demonstrate that mice were protected from death against challenges with H5N1 and H7N7, but that the protection was not complete as evidenced by severe clinical signs. In ferrets, protection against H7N9 was not observed. In contrast, reduced upper and lower respiratory tract viral loads and reduced lung pathology, was achieved in H5N1 challenged ferrets. Together these results suggest that, at least to some extent, Matrix-M adjuvated seasonal virosomal influenza vaccine can serve as an interim measure to decrease morbidity and mortality associated with a pandemic outbreak.

No MeSH data available.


Related in: MedlinePlus