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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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Lung viral titers and histopathological changes of vaccinated mice following challenge with live influenza Ah01/H7N9 virus.Two weeks after the boost, vaccinated mice were i.n. infected with Ah01/H7N9 (50LD50) and lung tissues were collected 3 days later. (A) Viral titers in the lung of infected mice. The data were determined in triplicate by CCID50 assay in MDCK cells 3 days post infection and expressed as log10 CCID50/g tissue. Data are means ± SD. *p<0.01; ** p<0.001 (B) Lung histopathological changes following virus challenge. Representative histopathological images of lung damage by H&E staining from five mice per group.
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pone.0123659.g006: Lung viral titers and histopathological changes of vaccinated mice following challenge with live influenza Ah01/H7N9 virus.Two weeks after the boost, vaccinated mice were i.n. infected with Ah01/H7N9 (50LD50) and lung tissues were collected 3 days later. (A) Viral titers in the lung of infected mice. The data were determined in triplicate by CCID50 assay in MDCK cells 3 days post infection and expressed as log10 CCID50/g tissue. Data are means ± SD. *p<0.01; ** p<0.001 (B) Lung histopathological changes following virus challenge. Representative histopathological images of lung damage by H&E staining from five mice per group.

Mentions: To quantify viral replication, lung tissues of infected mice were collected and used to inoculate cultured cells (Fig 6A). Importantly, viral titers in the lungs of mice vaccinated with the Ah01/AA ca vaccine were lower than those in control mice injected with PBS. Interestingly, no virus was detected in the lung tissues of mice immunized with 106 CCID50. These results suggest that the Ah01/AA ca vaccine elicited a protective immune response against live influenza H7N9 virus infection.


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)

Lung viral titers and histopathological changes of vaccinated mice following challenge with live influenza Ah01/H7N9 virus.Two weeks after the boost, vaccinated mice were i.n. infected with Ah01/H7N9 (50LD50) and lung tissues were collected 3 days later. (A) Viral titers in the lung of infected mice. The data were determined in triplicate by CCID50 assay in MDCK cells 3 days post infection and expressed as log10 CCID50/g tissue. Data are means ± SD. *p<0.01; ** p<0.001 (B) Lung histopathological changes following virus challenge. Representative histopathological images of lung damage by H&E staining from five mice per group.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4401572&req=5

pone.0123659.g006: Lung viral titers and histopathological changes of vaccinated mice following challenge with live influenza Ah01/H7N9 virus.Two weeks after the boost, vaccinated mice were i.n. infected with Ah01/H7N9 (50LD50) and lung tissues were collected 3 days later. (A) Viral titers in the lung of infected mice. The data were determined in triplicate by CCID50 assay in MDCK cells 3 days post infection and expressed as log10 CCID50/g tissue. Data are means ± SD. *p<0.01; ** p<0.001 (B) Lung histopathological changes following virus challenge. Representative histopathological images of lung damage by H&E staining from five mice per group.
Mentions: To quantify viral replication, lung tissues of infected mice were collected and used to inoculate cultured cells (Fig 6A). Importantly, viral titers in the lungs of mice vaccinated with the Ah01/AA ca vaccine were lower than those in control mice injected with PBS. Interestingly, no virus was detected in the lung tissues of mice immunized with 106 CCID50. These results suggest that the Ah01/AA ca vaccine elicited a protective immune response against live influenza H7N9 virus infection.

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