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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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Protective efficacy of Ah01/AA ca vaccine immunized mice against a lethal challenge with live influenza Ah01/H7N9 virus.Two weeks after boost, vaccinated mice were i.n infected with Ah01/H7N9 (50LD50) and monitored daily for 2 weeks post challenge. (A) Body weight change (%) of the mice. (B) Survival rate (%). Points represent means ± SD.
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pone.0123659.g005: Protective efficacy of Ah01/AA ca vaccine immunized mice against a lethal challenge with live influenza Ah01/H7N9 virus.Two weeks after boost, vaccinated mice were i.n infected with Ah01/H7N9 (50LD50) and monitored daily for 2 weeks post challenge. (A) Body weight change (%) of the mice. (B) Survival rate (%). Points represent means ± SD.

Mentions: To further evaluate the protective efficacy of the Ah01/AA ca vaccine against live H7N9 influenza virus, mice were challenged with wild-type Ah01/H7N9 (50LD50) at 2 weeks after boost. In the 106 CCID50 vaccinated group 100% mice survived for at least 14 days following challenge with the Ah01/H7N9 influenza virus, and their body weight recovered rapidly at 6 days post infection (Fig 5). On the contrary, mice in the 105 CCID50 vaccinated group exhibited a rapid decrease in body weight at day 5 post challenge, which resulted in a 70% survival rate. In contrast, in the 104 CCID50 vaccinated group 20% mice survived post challenge. As a comparison, all mice in control group died within 10 days. These results indicate that immunization with 106 CCID50 of the Ah01/AA ca vaccine completely protected mice against a live influenza H7N9 viral challenge.


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)

Protective efficacy of Ah01/AA ca vaccine immunized mice against a lethal challenge with live influenza Ah01/H7N9 virus.Two weeks after boost, vaccinated mice were i.n infected with Ah01/H7N9 (50LD50) and monitored daily for 2 weeks post challenge. (A) Body weight change (%) of the mice. (B) Survival rate (%). Points represent means ± SD.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0123659.g005: Protective efficacy of Ah01/AA ca vaccine immunized mice against a lethal challenge with live influenza Ah01/H7N9 virus.Two weeks after boost, vaccinated mice were i.n infected with Ah01/H7N9 (50LD50) and monitored daily for 2 weeks post challenge. (A) Body weight change (%) of the mice. (B) Survival rate (%). Points represent means ± SD.
Mentions: To further evaluate the protective efficacy of the Ah01/AA ca vaccine against live H7N9 influenza virus, mice were challenged with wild-type Ah01/H7N9 (50LD50) at 2 weeks after boost. In the 106 CCID50 vaccinated group 100% mice survived for at least 14 days following challenge with the Ah01/H7N9 influenza virus, and their body weight recovered rapidly at 6 days post infection (Fig 5). On the contrary, mice in the 105 CCID50 vaccinated group exhibited a rapid decrease in body weight at day 5 post challenge, which resulted in a 70% survival rate. In contrast, in the 104 CCID50 vaccinated group 20% mice survived post challenge. As a comparison, all mice in control group died within 10 days. These results indicate that immunization with 106 CCID50 of the Ah01/AA ca vaccine completely protected mice against a live influenza H7N9 viral challenge.

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