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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 H5N1.Mice (n = 9-10/group) were immunized 1x or 2x with TVV with or without MM. Four weeks later, mice were challenged with 25xLD50 wild-type A/Hong Kong /156/97 (H5N1) 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.g002: TVV+MM protects mice against avian H5N1.Mice (n = 9-10/group) were immunized 1x or 2x with TVV with or without MM. Four weeks later, mice were challenged with 25xLD50 wild-type A/Hong Kong /156/97 (H5N1) 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: After the lethal H5N1 challenge, all mice that received a single immunization with TVV alone succumbed to the infection, while a single immunization with TVV+MM partially protected the mice against death, although not significantly compared to PBS (p = 0.421). Two immunizations with the non-adjuvated vaccine did not improve survival proportions (p = 0.947 compared to PBS) whereas two immunizations with TVV+MM significantly increased survival proportions after H5N1 challenge compared to the vehicle control (p = 0.006) (Fig 2A and 2D). Accordingly, body weight-loss and clinical scores were significantly lower compared to PBS (p<0.001 for both) (Fig 2E and 2F).


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 H5N1.Mice (n = 9-10/group) were immunized 1x or 2x with TVV with or without MM. Four weeks later, mice were challenged with 25xLD50 wild-type A/Hong Kong /156/97 (H5N1) 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.g002: TVV+MM protects mice against avian H5N1.Mice (n = 9-10/group) were immunized 1x or 2x with TVV with or without MM. Four weeks later, mice were challenged with 25xLD50 wild-type A/Hong Kong /156/97 (H5N1) 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: After the lethal H5N1 challenge, all mice that received a single immunization with TVV alone succumbed to the infection, while a single immunization with TVV+MM partially protected the mice against death, although not significantly compared to PBS (p = 0.421). Two immunizations with the non-adjuvated vaccine did not improve survival proportions (p = 0.947 compared to PBS) whereas two immunizations with TVV+MM significantly increased survival proportions after H5N1 challenge compared to the vehicle control (p = 0.006) (Fig 2A and 2D). Accordingly, body weight-loss and clinical scores were significantly lower compared to PBS (p<0.001 for both) (Fig 2E and 2F).

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