Limits...
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.

Show MeSH

Related in: MedlinePlus

Live attenuated monovalent influenza A (H7N9) vaccines induce antibody responses in mice.Groups of mice were i.n. immunized at weeks 0 and 2 with various doses of 104 CCID50, 105 CCID50, and 106 CCID50 of the Ah01/AA ca vaccine or mock-infected with PBS. Levels of HI (A) and NT (B) antibodies against wt Influenza H7N9 virus in sera 2 weeks after prime and boost. Error bars indicate SDs (n = 8).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4401572&req=5

pone.0123659.g002: Live attenuated monovalent influenza A (H7N9) vaccines induce antibody responses in mice.Groups of mice were i.n. immunized at weeks 0 and 2 with various doses of 104 CCID50, 105 CCID50, and 106 CCID50 of the Ah01/AA ca vaccine or mock-infected with PBS. Levels of HI (A) and NT (B) antibodies against wt Influenza H7N9 virus in sera 2 weeks after prime and boost. Error bars indicate SDs (n = 8).

Mentions: Humoral immune responses induced by i.n. immunization of Ah01/AA ca vaccines were assessed by assaying HI and NT antibodies in the serum of vaccinated mice. As shown in Fig 2, the Ah01/AA ca vaccine induced a significantly stronger antibody response on day 14 following the boost in all groups, most notably in the 106 CCID50 group. A significant difference in HI titers was observed between the Ah01/AA ca vaccinated group and the PBS control group. Additionally, 14 days following the second vaccination, the HI antibody titer increased sharply to 1,280 in the 106 CCID50 group. The serum neutralizing antibody levels were also measured in the mice. Serum NT titers against wt Ah01/H7N9 virus were 60, 180, and 280 in the 104 CCID50, 105 CCID50, and 106 CCID50 vaccine groups, respectively, following two doses of vaccine. Concomitantly, the increase in NT titers in mouse sera corresponds with the change in HI titers.


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)

Live attenuated monovalent influenza A (H7N9) vaccines induce antibody responses in mice.Groups of mice were i.n. immunized at weeks 0 and 2 with various doses of 104 CCID50, 105 CCID50, and 106 CCID50 of the Ah01/AA ca vaccine or mock-infected with PBS. Levels of HI (A) and NT (B) antibodies against wt Influenza H7N9 virus in sera 2 weeks after prime and boost. Error bars indicate SDs (n = 8).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0123659.g002: Live attenuated monovalent influenza A (H7N9) vaccines induce antibody responses in mice.Groups of mice were i.n. immunized at weeks 0 and 2 with various doses of 104 CCID50, 105 CCID50, and 106 CCID50 of the Ah01/AA ca vaccine or mock-infected with PBS. Levels of HI (A) and NT (B) antibodies against wt Influenza H7N9 virus in sera 2 weeks after prime and boost. Error bars indicate SDs (n = 8).
Mentions: Humoral immune responses induced by i.n. immunization of Ah01/AA ca vaccines were assessed by assaying HI and NT antibodies in the serum of vaccinated mice. As shown in Fig 2, the Ah01/AA ca vaccine induced a significantly stronger antibody response on day 14 following the boost in all groups, most notably in the 106 CCID50 group. A significant difference in HI titers was observed between the Ah01/AA ca vaccinated group and the PBS control group. Additionally, 14 days following the second vaccination, the HI antibody titer increased sharply to 1,280 in the 106 CCID50 group. The serum neutralizing antibody levels were also measured in the mice. Serum NT titers against wt Ah01/H7N9 virus were 60, 180, and 280 in the 104 CCID50, 105 CCID50, and 106 CCID50 vaccine groups, respectively, following two doses of vaccine. Concomitantly, the increase in NT titers in mouse sera corresponds with the change in HI titers.

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