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Human adenovirus species B knob proteins as immunogens for inducing cross-neutralizing antibody responses
Zhenwei Liu1,2, Yuting Xian3, Jixian Lan4
1Department of Pediatrics, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Abstract:
The re-emerging human adenovirus (HAdV) types 3, 7, 14, and 55 of species B have caused severe or even fatal acute respiratory disease. Therefore, the development of multivalent vaccines against HAdV types 3, 7, 14, and 55 remains an important goal. In our previous study, we identified a cross-neutralizing epitope that induced broadly reactive monoclonal neutralizing antibodies against the knob proteins of HAdV types 7, 11, 14, and 55. To study the immunogenicity of HAdV species B knob proteins, we evaluated humoral immune responses to the knob proteins in vivo and in vitro. We found that the knob proteins elicited robust binding and neutralizing antibody responses after three immunizations of mice. In addition, mouse antisera raised against the knob proteins exhibited cross-neutralizing activity against original species B members. Furthermore, immunization with a mix of HAdV-3, 7, and 55 knob proteins protected Chinese tree shrews against an experimental HAdV challenge. Our results provide insight into the immunogenicity of HAdV species B knob proteins.IMPORTANCEHuman adenovirus (HAdV) species B are common pathogens causing severe pneumonia in children, and there is currently no vaccine available. Because there are many HAdV species B types, developing broad-spectrum vaccines against HAdV species B is an important research goal. Our study revealed that immunization with recombinant HAdV species B knob proteins effectively elicited cross-neutralizing antibody responses against original species B members with protective immunity. This study provides a novel insight into the immunogenicity of HAdV species B knob proteins.
Insights
Recombinant human adenovirus (HAdV) species B knob proteins effectively induce cross-neutralizing antibodies. Immunization with these proteins protected animals against HAdV challenge, offering a promising strategy for developing broad-spectrum HAdV vaccines.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Human adenovirus (HAdV) species B types 3, 7, 14, and 55 cause severe respiratory illness.
- There is a critical need for multivalent vaccines against these re-emerging HAdV strains.
- Current vaccines do not offer broad-spectrum protection against diverse HAdV species B types.
Purpose of the Study:
- To investigate the immunogenicity of HAdV species B knob proteins.
- To evaluate the potential of knob proteins in eliciting cross-neutralizing antibody responses.
- To assess the protective efficacy of HAdV knob protein immunization against HAdV challenge.
Main Methods:
- Evaluation of humoral immune responses to HAdV species B knob proteins in mice (in vivo and in vitro).
- Assessment of binding and neutralizing antibody titers post-immunization.
- Testing cross-neutralizing activity of antisera against various HAdV species B members.
- Challenging immunized Chinese tree shrews with HAdV to evaluate protection.
Main Results:
- HAdV species B knob proteins elicited robust binding and neutralizing antibody responses in mice after three immunizations.
- Mouse antisera demonstrated cross-neutralizing activity against original species B HAdV members.
- Immunization with a mix of HAdV-3, 7, and 55 knob proteins conferred protection in Chinese tree shrews against experimental HAdV challenge.
Conclusions:
- HAdV species B knob proteins are immunogenic and can induce broadly reactive neutralizing antibodies.
- Recombinant HAdV knob proteins represent a promising candidate for developing multivalent vaccines against severe HAdV respiratory infections.
- This study provides valuable insights into the immunogenicity of HAdV species B knob proteins for future vaccine design.
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