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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

Ferrets are partially protected against highly pathogenic H5N1 after TVV+MM vaccination.Groups of 7–8 ferrets received two intramuscular injections with TVV, TVV+MM, PBS, PBS+MM or inactivated H5H1 virus as positive control (Control). 4 weeks later the animals were challenged with a sub-lethal dose of 104 TCID50 of influenza A H5N1 A/Indonesia/05/2005. Ferrets were monitored for 4 consecutive days and sacrificed at day 4 post challenge. (A) Infectious viral load in lung tissue (B) infectious throat viral load (day 1 to 4), (C) percentage of body weight change during the observation period and (D) lung weight as determined after sacrifice. Dots indicate individual animals and horizontal lines represent group means (A and D). Lines represent group mean with 95% confidence interval (B) or the interquartile range (C). Asterisks indicate statistically significant differences compared to PBS injected animals (*p<0.05, **p<0.01, ***p<0.001, according to the materials and methods section).
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pone.0135723.g004: Ferrets are partially protected against highly pathogenic H5N1 after TVV+MM vaccination.Groups of 7–8 ferrets received two intramuscular injections with TVV, TVV+MM, PBS, PBS+MM or inactivated H5H1 virus as positive control (Control). 4 weeks later the animals were challenged with a sub-lethal dose of 104 TCID50 of influenza A H5N1 A/Indonesia/05/2005. Ferrets were monitored for 4 consecutive days and sacrificed at day 4 post challenge. (A) Infectious viral load in lung tissue (B) infectious throat viral load (day 1 to 4), (C) percentage of body weight change during the observation period and (D) lung weight as determined after sacrifice. Dots indicate individual animals and horizontal lines represent group means (A and D). Lines represent group mean with 95% confidence interval (B) or the interquartile range (C). Asterisks indicate statistically significant differences compared to PBS injected animals (*p<0.05, **p<0.01, ***p<0.001, according to the materials and methods section).

Mentions: Immunizations with TVV+MM resulted in a statistically significant 4.5-fold reduction in H5N1 infectious viral titers in the lung compared to animals injected with PBS only (p = 0.011) (Fig 4A). In addition, ferrets immunized with TVV+MM showed statistically significant reduced throat viral titers compared to the viral titers in the throats of animals receiving PBS (p<0.001) (Fig 4B).


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)

Ferrets are partially protected against highly pathogenic H5N1 after TVV+MM vaccination.Groups of 7–8 ferrets received two intramuscular injections with TVV, TVV+MM, PBS, PBS+MM or inactivated H5H1 virus as positive control (Control). 4 weeks later the animals were challenged with a sub-lethal dose of 104 TCID50 of influenza A H5N1 A/Indonesia/05/2005. Ferrets were monitored for 4 consecutive days and sacrificed at day 4 post challenge. (A) Infectious viral load in lung tissue (B) infectious throat viral load (day 1 to 4), (C) percentage of body weight change during the observation period and (D) lung weight as determined after sacrifice. Dots indicate individual animals and horizontal lines represent group means (A and D). Lines represent group mean with 95% confidence interval (B) or the interquartile range (C). Asterisks indicate statistically significant differences compared to PBS injected animals (*p<0.05, **p<0.01, ***p<0.001, according to the materials and methods section).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0135723.g004: Ferrets are partially protected against highly pathogenic H5N1 after TVV+MM vaccination.Groups of 7–8 ferrets received two intramuscular injections with TVV, TVV+MM, PBS, PBS+MM or inactivated H5H1 virus as positive control (Control). 4 weeks later the animals were challenged with a sub-lethal dose of 104 TCID50 of influenza A H5N1 A/Indonesia/05/2005. Ferrets were monitored for 4 consecutive days and sacrificed at day 4 post challenge. (A) Infectious viral load in lung tissue (B) infectious throat viral load (day 1 to 4), (C) percentage of body weight change during the observation period and (D) lung weight as determined after sacrifice. Dots indicate individual animals and horizontal lines represent group means (A and D). Lines represent group mean with 95% confidence interval (B) or the interquartile range (C). Asterisks indicate statistically significant differences compared to PBS injected animals (*p<0.05, **p<0.01, ***p<0.001, according to the materials and methods section).
Mentions: Immunizations with TVV+MM resulted in a statistically significant 4.5-fold reduction in H5N1 infectious viral titers in the lung compared to animals injected with PBS only (p = 0.011) (Fig 4A). In addition, ferrets immunized with TVV+MM showed statistically significant reduced throat viral titers compared to the viral titers in the throats of animals receiving PBS (p<0.001) (Fig 4B).

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