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Generation of a broadly reactive influenza H1 antigen using a consensus HA sequence
Xianqiang Ping1, Weibin Hu1, Rui Xiong2
1CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 YueYang Road, Shanghai 200031, China.
Vaccine
|July 2, 2018
Summary
Researchers developed a universal H1 influenza antigen (CH1) from consensus HA sequences. This antigen, when used in a chimeric virus vaccine, provided broad protection against various H1N1 strains in mice.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Influenza A virus subtype H1N1 causes significant human illness, necessitating annual vaccine updates due to viral evolution.
- Existing H1N1 vaccines offer limited protection against future or drifted strains, highlighting the need for broader immunity.
- The hemagglutinin (HA) protein is a key target for influenza vaccines, but its variability poses a challenge.
Purpose of the Study:
- To develop a universal H1 hemagglutinin (HA) antigen for broader influenza A virus subtype H1N1 protection.
- To assess the immunogenicity and protective efficacy of vaccines based on the consensus H1 antigen.
- To evaluate a novel chimeric virus vaccine strategy for H1N1 influenza.
Main Methods:
- Downloaded and analyzed 2,656 human H1N1 HA protein sequences to construct a phylogenetic tree.
- Generated a consensus H1 protein (CH1) incorporating conserved T-cell and B-cell epitopes.
- Developed DNA vaccines and a recombinant chimeric PR8-CH1 virus expressing the CH1 antigen for animal studies.
Main Results:
- A consensus H1 protein (CH1) was created, showing genetic similarity to historical H1N1 isolates.
- DNA vaccination with CH1 induced broad T-cell and B-cell responses but did not fully neutralize pdm09 H1N1.
- A combination vaccine (CH1 and pdm09 HA) neutralized pdm09 H1N1 and protected mice; the PR8-CH1 virus vaccine provided complete protection against heterologous H1N1 strains and was highly attenuated.
Conclusions:
- A universal H1 antigen (CH1) can be constructed from consensus HA sequences.
- The PR8-CH1 chimeric virus vaccine elicits broadly protective immunity against diverse H1N1 strains.
- This approach offers a promising strategy for developing a more universal and effective H1N1 influenza vaccine.
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