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Enhanced immunogenicity following miR-155 incorporation into the influenza A virus genome
Leonard Izzard1, Daniel Dlugolenski1, Yingju Xia1
1School of Medicine, Deakin University, Waurn Ponds, VIC, Australia; Australian Animal Health Laboratory, CSIRO, Geelong, VIC, Australia.
Abstract:
Influenza A vaccine efficacy in the elderly is generally poor and so identification of novel molecular adjuvants to improve immunogenicity is important to reduce the overall burden of disease. Short non-coding RNAs, known as microRNAs (miRNAs) are known to regulate gene expression and have the potential to influence immune responses. One such miRNA, miR-155, has been shown to modulate T and B cell development and function. We incorporated miR-155 into the influenza A virus (IAV) genome creating a self-adjuvanting 'live vaccine' with the ability to modify immunogenicity. Infection of mice with a recombinant influenza virus encoding miR-155 in the NS gene segment altered epitope-specific expansion of influenza-specific CD8+ T cells and induced significantly higher levels of neutralising antibody.
Insights
This study engineered a live influenza A vaccine incorporating microRNA-155 (miR-155) to boost immune responses in elderly individuals. The novel vaccine enhanced T cell expansion and neutralising antibody levels, improving vaccine immunogenicity.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Influenza A vaccine efficacy is limited in the elderly.
- Novel molecular adjuvants are needed to improve vaccine immunogenicity.
- MicroRNAs (miRNAs) regulate gene expression and immune responses.
Purpose of the Study:
- To develop a self-adjuvanting live influenza A vaccine.
- To enhance the immunogenicity of influenza A vaccines using miR-155.
- To investigate the impact of miR-155 on immune responses to influenza A virus.
Main Methods:
- Incorporation of miR-155 into the influenza A virus (IAV) genome.
- Generation of a recombinant live influenza vaccine encoding miR-155.
- Infection of mice with the recombinant IAV to assess immune responses.
Main Results:
- Recombinant IAV encoding miR-155 altered epitope-specific CD8+ T cell expansion.
- Significantly higher levels of neutralising antibodies were induced by the miR-155 IAV.
- The modified live vaccine demonstrated enhanced immunogenicity.
Conclusions:
- Incorporating miR-155 into the IAV genome creates a self-adjuvanting vaccine.
- This approach improves T cell responses and neutralising antibody production.
- This strategy holds potential for enhancing influenza vaccine efficacy, particularly in vulnerable populations like the elderly.