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Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies
Published on: August 29, 2017
Mimotopes selected with neutralizing antibodies against multiple subtypes of influenza A
Yanwei Zhong1, Jiong Cai, Chuanfu Zhang
1Institute of Infectious Diseases, Beijing 302 Hospital, Beijing, China. zhongyanwei@126.com
Background:
The mimotopes of viruses are considered as the good targets for vaccine design. We prepared mimotopes against multiple subtypes of influenza A and evaluate their immune responses in flu virus challenged Balb/c mice.
Methods:
The mimotopes of influenza A including pandemic H1N1, H3N2, H2N2 and H1N1 swine-origin influenza virus were screened by peptide phage display libraries, respectively. These mimotopes were engineered in one protein as multi- epitopes in Escherichia coli (E. coli) and purified. Balb/c mice were immunized using the multi-mimotopes protein and specific antibody responses were analyzed using hemagglutination inhibition (HI) assay and enzyme-linked immunosorbent assay (ELISA). The lung inflammation level was evaluated by hematoxylin and eosin (HE).
Results:
Linear heptopeptide and dodecapeptide mimotopes were obtained for these influenza virus. The recombinant multi-mimotopes protein was a 73 kDa fusion protein. Comparing immunized infected groups with unimmunized infected subsets, significant differences were observed in the body weight loss and survival rate. The antiserum contained higher HI Ab titer against H1N1 virus and the lung inflammation level were significantly decreased in immunized infected groups.
Conclusions:
Phage-displayed mimotopes against multiple subtypes of influenza A were accessible to the mouse immune system and triggered a humoral response to above virus.
Insights
Mimotopes targeting multiple influenza A virus subtypes were developed and tested in mice. These mimotopes successfully elicited immune responses, reducing lung inflammation and improving survival rates in challenged mice.
Area of Science:
- Vaccinology
- Immunology
- Virology
Background:
- Mimotopes, which mimic viral epitopes, are promising targets for vaccine development.
- This study focuses on developing mimotopes against diverse influenza A virus subtypes.
Purpose of the Study:
- To create and evaluate multi-epitope mimotopes derived from various influenza A virus strains for vaccine potential.
- To assess the immunogenicity and protective efficacy of these mimotopes in a mouse model.
Main Methods:
- Peptide phage display libraries were used to screen mimotopes for pandemic H1N1, H3N2, H2N2, and swine-origin H1N1 influenza A viruses.
- Engineered multi-epitope mimotopes were expressed in Escherichia coli, purified, and used to immunize Balb/c mice.
- Immune responses were analyzed via hemagglutination inhibition (HI) and enzyme-linked immunosorbent assays (ELISA), with lung inflammation assessed by hematoxylin and eosin (HE) staining.
Main Results:
- Linear heptapeptide and dodecapeptide mimotopes were identified for the targeted influenza A virus subtypes.
- A 73 kDa recombinant multi-mimotope fusion protein was successfully produced.
- Immunized mice showed significantly reduced body weight loss, improved survival rates, higher HI antibody titers against H1N1, and decreased lung inflammation compared to controls.
Conclusions:
- Phage-displayed mimotopes targeting multiple influenza A virus subtypes are immunogenic in mice.
- These mimotopes effectively induce a humoral immune response against influenza A viruses, demonstrating potential for vaccine development.
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