AI Article Synopsis
- The development of a universal influenza vaccine is crucial due to the virus's high mutation rate, and the M2e protein is a promising target for this purpose.
- Two recombinant live attenuated influenza vaccine (LAIV) candidates were created, both showing increased immune response compared to a control strain in ferrets, with the LAIV/HA+4M2e proving to be the most effective.
- The LAIV/HA+4M2e vaccine not only provided significant protection against various strains but also demonstrated a favorable safety profile, making it a strong candidate for phase I clinical trials.
Article Abstract
The development of an influenza vaccine with broad protection and durability remains an attractive idea due to the high mutation rate of the influenza virus. An extracellular domain of Matrix 2 protein (M2e) is among the most attractive target for the universal influenza vaccine owing to its high conservancy rate. Here, we generated two recombinant live attenuated influenza vaccine (LAIV) candidates encoding four M2e epitopes representing consensus sequences of human, avian and swine influenza viruses, and studied them in a preclinical ferret model. Both LAIV+4M2e viruses induced higher levels of M2e-specific antibodies compared to the control LAIV strain, with the LAIV/HA+4M2e candidate being significantly more immunogenic than the LAIV/NS+4M2e counterpart. A high-dose heterosubtypic influenza virus challenge revealed the highest degree of protection after immunization with LAIV/HA+4M2e strain, followed by the NS-modified LAIV and the classical LAIV virus. Furthermore, only the immune sera from the LAIV/HA+4M2e-immunized ferrets protected mice from a panel of lethal influenza viruses encoding M genes of various origins. These data suggest that the improved cross-protection of the LAIV/HA+4M2e universal influenza vaccine candidate was mediated by the M2e-targeted antibodies. Taking into account the safety profile and improved cross-protective potential, the LAIV/HA+4M2e vaccine warrants its further evaluation in a phase I clinical trial.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310119 | PMC |
| http://dx.doi.org/10.3390/v13071280 | DOI Listing |
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