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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 induces cross-reactive H5 and H7 antibody responses.Mice (n = 9-10/group) were immunized 1x or 2x with TVV with or without MM. 27 days later (1 day before challenge) individual serum samples were obtained and tested for (A) vaccine homologous recH1 of A/California/07/07, (B) vaccine homologous recH3 of the A/Victoria/210/09-like A/Perth/16/09 (98.8% homologous), (C) recH5 of A/Hong Kong/156/97, and (D) recH7 of A/Netherlands/219/03 (99.6% homologous to the challenge strain A/chicken/Netherlands/621557/03) antibody responses. Serum pools of mice (n = 50/group) that received 1x or 2x TVV+MM or no immunization (-) were tested for (E) vaccine homologous recN1 A/California/04/09 and (F) recN1 of A/Hong Kong/156/97 reactive antibody responses. Black bars indicate medians of log-10 transformed ELISA titers (EU). 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.g001: TVV+MM induces cross-reactive H5 and H7 antibody responses.Mice (n = 9-10/group) were immunized 1x or 2x with TVV with or without MM. 27 days later (1 day before challenge) individual serum samples were obtained and tested for (A) vaccine homologous recH1 of A/California/07/07, (B) vaccine homologous recH3 of the A/Victoria/210/09-like A/Perth/16/09 (98.8% homologous), (C) recH5 of A/Hong Kong/156/97, and (D) recH7 of A/Netherlands/219/03 (99.6% homologous to the challenge strain A/chicken/Netherlands/621557/03) antibody responses. Serum pools of mice (n = 50/group) that received 1x or 2x TVV+MM or no immunization (-) were tested for (E) vaccine homologous recN1 A/California/04/09 and (F) recN1 of A/Hong Kong/156/97 reactive antibody responses. Black bars indicate medians of log-10 transformed ELISA titers (EU). 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: To investigate the immune potentiating properties of MM, mice were immunized once or twice with TVV or TVV combined with MM (TVV+MM). Four weeks later individual serum samples were collected and vaccine homologous and challenge strain matching HA-specific antibody responses were determined. One and two immunizations with TVV alone yielded in statistically significant vaccine homologous H1 titers as compared to the vehicle control group (p<0.001 for both). The addition of MM increased the H1-specific antibody titers (p<0.001 for both compared to 1x and 2x TVV) (Fig 1A). A similar pattern of antibody responses were observed against vaccine homologous H3 demonstrating that immunizations with 1x or 2x TVV resulted in statistically significant induction of H3-spefific antibody titers as compared to the vehicle control group (PBS injected mice) (p<0.001 for both). The H3-specific antibody response was enhanced by adjuvation of TVV with MM (p<0.001 for both compared to 1x and 2x TVV) (Fig 1B). Next we assessed whether the improved vaccine homologous H1 and H3-specific antibody responses would translate in induction of cross-reactive antibody responses against the HA of avian H5 and H7 strains. Immunization with TVV alone did not result in significant levels of cross-reactive H5-specific antibody titers as compared to the vehicle control group. However, a single immunization with MM adjuvated TVV was sufficient to induce significantly higher antibody titers against H5 compared to the vehicle control group (p<0.001). A second immunization with TVV+MM further enhanced the H5-specific antibody response (p = 0.002 compared to 1xTVV+MM) (Fig 1C).


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 induces cross-reactive H5 and H7 antibody responses.Mice (n = 9-10/group) were immunized 1x or 2x with TVV with or without MM. 27 days later (1 day before challenge) individual serum samples were obtained and tested for (A) vaccine homologous recH1 of A/California/07/07, (B) vaccine homologous recH3 of the A/Victoria/210/09-like A/Perth/16/09 (98.8% homologous), (C) recH5 of A/Hong Kong/156/97, and (D) recH7 of A/Netherlands/219/03 (99.6% homologous to the challenge strain A/chicken/Netherlands/621557/03) antibody responses. Serum pools of mice (n = 50/group) that received 1x or 2x TVV+MM or no immunization (-) were tested for (E) vaccine homologous recN1 A/California/04/09 and (F) recN1 of A/Hong Kong/156/97 reactive antibody responses. Black bars indicate medians of log-10 transformed ELISA titers (EU). 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.g001: TVV+MM induces cross-reactive H5 and H7 antibody responses.Mice (n = 9-10/group) were immunized 1x or 2x with TVV with or without MM. 27 days later (1 day before challenge) individual serum samples were obtained and tested for (A) vaccine homologous recH1 of A/California/07/07, (B) vaccine homologous recH3 of the A/Victoria/210/09-like A/Perth/16/09 (98.8% homologous), (C) recH5 of A/Hong Kong/156/97, and (D) recH7 of A/Netherlands/219/03 (99.6% homologous to the challenge strain A/chicken/Netherlands/621557/03) antibody responses. Serum pools of mice (n = 50/group) that received 1x or 2x TVV+MM or no immunization (-) were tested for (E) vaccine homologous recN1 A/California/04/09 and (F) recN1 of A/Hong Kong/156/97 reactive antibody responses. Black bars indicate medians of log-10 transformed ELISA titers (EU). 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: To investigate the immune potentiating properties of MM, mice were immunized once or twice with TVV or TVV combined with MM (TVV+MM). Four weeks later individual serum samples were collected and vaccine homologous and challenge strain matching HA-specific antibody responses were determined. One and two immunizations with TVV alone yielded in statistically significant vaccine homologous H1 titers as compared to the vehicle control group (p<0.001 for both). The addition of MM increased the H1-specific antibody titers (p<0.001 for both compared to 1x and 2x TVV) (Fig 1A). A similar pattern of antibody responses were observed against vaccine homologous H3 demonstrating that immunizations with 1x or 2x TVV resulted in statistically significant induction of H3-spefific antibody titers as compared to the vehicle control group (PBS injected mice) (p<0.001 for both). The H3-specific antibody response was enhanced by adjuvation of TVV with MM (p<0.001 for both compared to 1x and 2x TVV) (Fig 1B). Next we assessed whether the improved vaccine homologous H1 and H3-specific antibody responses would translate in induction of cross-reactive antibody responses against the HA of avian H5 and H7 strains. Immunization with TVV alone did not result in significant levels of cross-reactive H5-specific antibody titers as compared to the vehicle control group. However, a single immunization with MM adjuvated TVV was sufficient to induce significantly higher antibody titers against H5 compared to the vehicle control group (p<0.001). A second immunization with TVV+MM further enhanced the H5-specific antibody response (p = 0.002 compared to 1xTVV+MM) (Fig 1C).

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