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Immunization with a live attenuated H7N9 influenza vaccine protects mice against lethal challenge.

Yang X, Zhao J, Wang C, Duan Y, Zhao Z, Chen R, Zhang L, Xing L, Lai C, Zhang S, Wang X, Yang P - PLoS ONE (2015)

Bottom Line: The emergence of severe cases of human influenza A (H7N9) viral infection in China in the spring of 2003 resulted in a global effort to rapidly develop an effective candidate vaccine.Intranasal immunization of female BALB/c mice with Ah01/AA ca twice at a 2-week interval induced robust humoral, mucosal, and cell-mediated immune responses in a dose-dependent manner.Taken together, these data support the further evaluation of this Ah01/AA ca candidate vaccine in primates.

View Article: PubMed Central - PubMed

Affiliation: Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing, China.

ABSTRACT
The emergence of severe cases of human influenza A (H7N9) viral infection in China in the spring of 2003 resulted in a global effort to rapidly develop an effective candidate vaccine. In this study, a cold-adapted (ca), live attenuated monovalent reassortant influenza H7N9 virus (Ah01/AA ca) was generated using reverse genetics that contained hemagglutinin (HA) and neuraminidase (NA) genes from a 2013 pandemic A H7N9 isolate, A/Anhui/01/2013 virus (Ah01/H7N9); the remaining six backbone genes derived from the cold-adapted influenza H2N2 A/Ann Arbor/6/60 virus (AA virus). Ah01/AA ca virus exhibited temperature sensitivity (ts), ca, and attenuation (att) phenotypes. Intranasal immunization of female BALB/c mice with Ah01/AA ca twice at a 2-week interval induced robust humoral, mucosal, and cell-mediated immune responses in a dose-dependent manner. Furthermore, the candidate Ah01/AA ca virus was immunogenic and offered partial or complete protection of mice against a lethal challenge by the live 2013 influenza A H7N9 (A/Anhui/01/2013). Protection was demonstrated by the inhibition of viral replication and the attenuation of histopathological changes in the challenged mouse lung. Taken together, these data support the further evaluation of this Ah01/AA ca candidate vaccine in primates.

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Mucosal antibody response in BALB/c mice.Secretory IgA antibody levels against the influenza Ah01/AA ca vaccine antigen were assessed by ELISA in both nasal and lung lavage fluid from mice i.n. immunized with 104 CCID50, 105 CCID50, or 106 CCID50 of the Ah01/AA ca vaccine or mock-infected with PBS. Nasal and lung lavages were collected 2 weeks after the boost. The values are means ± SD from five mice. * p < 0.01 and ** p < 0.001.
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pone.0123659.g003: Mucosal antibody response in BALB/c mice.Secretory IgA antibody levels against the influenza Ah01/AA ca vaccine antigen were assessed by ELISA in both nasal and lung lavage fluid from mice i.n. immunized with 104 CCID50, 105 CCID50, or 106 CCID50 of the Ah01/AA ca vaccine or mock-infected with PBS. Nasal and lung lavages were collected 2 weeks after the boost. The values are means ± SD from five mice. * p < 0.01 and ** p < 0.001.

Mentions: ELISAs were conducted to determine whether A H7N9 IgA antibodies are detectable in mucosal lavage from mice immunized with the Ah01/AA ca vaccine. In all vaccinated groups, sIgA antibodies against the Ah01/H7N9 virus were tested in the nasal and lung lavages of mice using ELISA plates coated with purified H7N9 viral antigens at 14 days after boost; levels increased in a dose-dependent manner. A viral dose of 106 CCID50 Ah01/AA ca elicited a stronger sIgA antibody response in the lung lavage fluid compared to that in the nasal lavage fluid in response to the Ah01/H7N9 virus (titers of 1:290 and 1:16, respectively) (Fig 3). These data suggest that intranasal administration enhances mucosal antibody production in response to A H7N9 vaccination.


Immunization with a live attenuated H7N9 influenza vaccine protects mice against lethal challenge.

Yang X, Zhao J, Wang C, Duan Y, Zhao Z, Chen R, Zhang L, Xing L, Lai C, Zhang S, Wang X, Yang P - PLoS ONE (2015)

Mucosal antibody response in BALB/c mice.Secretory IgA antibody levels against the influenza Ah01/AA ca vaccine antigen were assessed by ELISA in both nasal and lung lavage fluid from mice i.n. immunized with 104 CCID50, 105 CCID50, or 106 CCID50 of the Ah01/AA ca vaccine or mock-infected with PBS. Nasal and lung lavages were collected 2 weeks after the boost. The values are means ± SD from five mice. * p < 0.01 and ** p < 0.001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401572&req=5

pone.0123659.g003: Mucosal antibody response in BALB/c mice.Secretory IgA antibody levels against the influenza Ah01/AA ca vaccine antigen were assessed by ELISA in both nasal and lung lavage fluid from mice i.n. immunized with 104 CCID50, 105 CCID50, or 106 CCID50 of the Ah01/AA ca vaccine or mock-infected with PBS. Nasal and lung lavages were collected 2 weeks after the boost. The values are means ± SD from five mice. * p < 0.01 and ** p < 0.001.
Mentions: ELISAs were conducted to determine whether A H7N9 IgA antibodies are detectable in mucosal lavage from mice immunized with the Ah01/AA ca vaccine. In all vaccinated groups, sIgA antibodies against the Ah01/H7N9 virus were tested in the nasal and lung lavages of mice using ELISA plates coated with purified H7N9 viral antigens at 14 days after boost; levels increased in a dose-dependent manner. A viral dose of 106 CCID50 Ah01/AA ca elicited a stronger sIgA antibody response in the lung lavage fluid compared to that in the nasal lavage fluid in response to the Ah01/H7N9 virus (titers of 1:290 and 1:16, respectively) (Fig 3). These data suggest that intranasal administration enhances mucosal antibody production in response to A H7N9 vaccination.

Bottom Line: The emergence of severe cases of human influenza A (H7N9) viral infection in China in the spring of 2003 resulted in a global effort to rapidly develop an effective candidate vaccine.Intranasal immunization of female BALB/c mice with Ah01/AA ca twice at a 2-week interval induced robust humoral, mucosal, and cell-mediated immune responses in a dose-dependent manner.Taken together, these data support the further evaluation of this Ah01/AA ca candidate vaccine in primates.

View Article: PubMed Central - PubMed

Affiliation: Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing, China.

ABSTRACT
The emergence of severe cases of human influenza A (H7N9) viral infection in China in the spring of 2003 resulted in a global effort to rapidly develop an effective candidate vaccine. In this study, a cold-adapted (ca), live attenuated monovalent reassortant influenza H7N9 virus (Ah01/AA ca) was generated using reverse genetics that contained hemagglutinin (HA) and neuraminidase (NA) genes from a 2013 pandemic A H7N9 isolate, A/Anhui/01/2013 virus (Ah01/H7N9); the remaining six backbone genes derived from the cold-adapted influenza H2N2 A/Ann Arbor/6/60 virus (AA virus). Ah01/AA ca virus exhibited temperature sensitivity (ts), ca, and attenuation (att) phenotypes. Intranasal immunization of female BALB/c mice with Ah01/AA ca twice at a 2-week interval induced robust humoral, mucosal, and cell-mediated immune responses in a dose-dependent manner. Furthermore, the candidate Ah01/AA ca virus was immunogenic and offered partial or complete protection of mice against a lethal challenge by the live 2013 influenza A H7N9 (A/Anhui/01/2013). Protection was demonstrated by the inhibition of viral replication and the attenuation of histopathological changes in the challenged mouse lung. Taken together, these data support the further evaluation of this Ah01/AA ca candidate vaccine in primates.

Show MeSH
Related in: MedlinePlus