Objective To evaluate the effect of intranasal immunization with CTA1-DD as mucosal adjuvant combined with H3N2 split vaccine. Methods Mice were immunized intranasally with PBS(negative control), or H3N2 split vaccine...Objective To evaluate the effect of intranasal immunization with CTA1-DD as mucosal adjuvant combined with H3N2 split vaccine. Methods Mice were immunized intranasally with PBS(negative control), or H3N2 split vaccine(3 μg/mouse) alone, or CTA1-DD(5 μg/mouse) alone, or H3N2 split vaccine(3 μg/mouse) plus CTA1-DD(5 μg/mouse). Positive control mice were immunized intramuscularly with H3N2 split vaccine(3 μg/mouse) and alum adjuvant. All the mice were immunized twice, two weeks apart. Then sera and mucosal lavages were collected. The specific HI titers, IgM, IgG, IgA, and IgG subtypes were examined by ELISA. IFN-γ and IL-4 were test by ELISpot. In addition, two weeks after the last immunization, surivival after H3N2 virus lethal challenge was measured. Results H3N2 split vaccine formulated with CTA1-DD could elicit higher Ig M, Ig G and hemagglutination inhibition titers in sera. Furthermore, using CTA1-DD as adjuvant significantly improved mucosal secretory Ig A titers in bronchoalveolar lavages and vaginal lavages. Meanwhile this mucosal adjuvant could enhance Th-1-type responses and induce protective hemagglutination inhibition titers. Notably, the addition of CTA1-DD to split vaccine provided 100% protection against lethal infection by the H3N2 virus. Conclusion CTA1-DD could promote mucosal, humoral and cell-mediated immune responses, which supports the further development of CTA1-DD as a mucosal adjuvant for mucosal vaccines.展开更多
The novel influenza A （H1N1） 2009 virus has emerged to cause the first pandemic of the twenty-first century. Disease outbreaks caused by the influenza A （H 1N 1） virus have prompted concerns about the potential fo...The novel influenza A （H1N1） 2009 virus has emerged to cause the first pandemic of the twenty-first century. Disease outbreaks caused by the influenza A （H 1N 1） virus have prompted concerns about the potential for a pandemic and have driven the development of vaccines against this subtype of influenza A. In this study, we developed a monovalent influenza A （H 1N 1） split vaccine and evaluated its effects in BALB/c mice. Mice were immunized subcutaneously with 2 doses of the vaccine containing hemagglutinin （HA） alone or HA plus an aluminum hydroxide （AI（OH）3） adjuvant. Immunization with varying doses of HA （3.75, 7.5, 15, 30, 45 or 60μg） was performed to induce the production of neutralizing antibodies. The vaccine elicited strong hemagglutination inhibition （HI） and microneutralization, and addition of the adjuvant augmented the antibody response. A preliminary safety evaluation showed that the vaccine was not toxic at large doses （0.5 ml containing 60 μg HA＋600 μg AI（OH）3 or 60 μg HA）. Moreover, the vaccine was found to be safe at a dose of 120 μg HA＋ 1200 μg AI（OH）3 or 120 μg HA in 1.0 ml in rats. In conclusion; the present study provides support for the clinical evaluation of influenza A （H1N1） vaccination as a public health intervention to mitigate a possible pandemic. Additionally, our findings support the further evaluation of the vaccine used in this study in primates or humans.展开更多
基金supported by the Chinese National Science and Technology Major Project for Important Infectious Diseases Control and Prevention [Grant No.2017ZX10105015001002]
文摘Objective To evaluate the effect of intranasal immunization with CTA1-DD as mucosal adjuvant combined with H3N2 split vaccine. Methods Mice were immunized intranasally with PBS(negative control), or H3N2 split vaccine(3 μg/mouse) alone, or CTA1-DD(5 μg/mouse) alone, or H3N2 split vaccine(3 μg/mouse) plus CTA1-DD(5 μg/mouse). Positive control mice were immunized intramuscularly with H3N2 split vaccine(3 μg/mouse) and alum adjuvant. All the mice were immunized twice, two weeks apart. Then sera and mucosal lavages were collected. The specific HI titers, IgM, IgG, IgA, and IgG subtypes were examined by ELISA. IFN-γ and IL-4 were test by ELISpot. In addition, two weeks after the last immunization, surivival after H3N2 virus lethal challenge was measured. Results H3N2 split vaccine formulated with CTA1-DD could elicit higher Ig M, Ig G and hemagglutination inhibition titers in sera. Furthermore, using CTA1-DD as adjuvant significantly improved mucosal secretory Ig A titers in bronchoalveolar lavages and vaginal lavages. Meanwhile this mucosal adjuvant could enhance Th-1-type responses and induce protective hemagglutination inhibition titers. Notably, the addition of CTA1-DD to split vaccine provided 100% protection against lethal infection by the H3N2 virus. Conclusion CTA1-DD could promote mucosal, humoral and cell-mediated immune responses, which supports the further development of CTA1-DD as a mucosal adjuvant for mucosal vaccines.
文摘The novel influenza A （H1N1） 2009 virus has emerged to cause the first pandemic of the twenty-first century. Disease outbreaks caused by the influenza A （H 1N 1） virus have prompted concerns about the potential for a pandemic and have driven the development of vaccines against this subtype of influenza A. In this study, we developed a monovalent influenza A （H 1N 1） split vaccine and evaluated its effects in BALB/c mice. Mice were immunized subcutaneously with 2 doses of the vaccine containing hemagglutinin （HA） alone or HA plus an aluminum hydroxide （AI（OH）3） adjuvant. Immunization with varying doses of HA （3.75, 7.5, 15, 30, 45 or 60μg） was performed to induce the production of neutralizing antibodies. The vaccine elicited strong hemagglutination inhibition （HI） and microneutralization, and addition of the adjuvant augmented the antibody response. A preliminary safety evaluation showed that the vaccine was not toxic at large doses （0.5 ml containing 60 μg HA＋600 μg AI（OH）3 or 60 μg HA）. Moreover, the vaccine was found to be safe at a dose of 120 μg HA＋ 1200 μg AI（OH）3 or 120 μg HA in 1.0 ml in rats. In conclusion; the present study provides support for the clinical evaluation of influenza A （H1N1） vaccination as a public health intervention to mitigate a possible pandemic. Additionally, our findings support the further evaluation of the vaccine used in this study in primates or humans.
