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Intranasal M2SR and BM2SR Vaccine Viruses Do Not Shed or Transmit in Ferrets
Yasuko Hatta1, Lindsay Hill-Batorski1, Michael J Moser1
1FluGen, Inc., Madison, WI 53711, USA.
Background/Objectives:
Live influenza vaccines are considered to stimulate better overall immune responses but are associated with safety concerns regarding shedding and the potential for transmission or reassortment with wild-type influenza viruses. Intranasal M2SR and BM2SR (M2- and BM2-deficient single replication), intranasal influenza viruses, have shown promise as broadly cross-reactive next-generation influenza vaccines. The replication deficiency, shedding, and transmissibility of M2SR/BM2SR viruses were evaluated in a ferret model.
Methods:
Wild-type influenza A and B control viruses replicated in upper respiratory organs and transmitted to both direct and aerosol contact ferrets, whereas M2SR and BM2SR influenza vaccine viruses were not detected in any tissues or in nasal washes after inoculation and were not recovered from any direct or aerosol contact ferrets. Mice were simultaneously infected with wild-type influenza A and M2SR viruses to assess reassortment potential. Sequence and PCR analyses of the genome recovered from individual virus plaques isolated from lung homogenates identified the origin of the segments as exclusively from the replicating wild-type virus.
Results:
These results indicate that M2SR and BM2SR influenza vaccine viruses are attenuated, do not shed or transmit, and have a low probability for reassortment after coinfection. Absence of shedding was further demonstrated in nasal swabs taken from subjects who were inoculated with H3N2 M2SR in a previously described Phase 1 clinical study.
Conclusions:
These results indicate that M2SR/BM2SR viruses have the potential to be used in a broader population range than current live influenza vaccines.
Insights
New intranasal influenza vaccines (M2SR/BM2SR) show promise for broad protection. These attenuated viruses do not shed or transmit, offering a safer alternative to current live influenza vaccines.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Live influenza vaccines offer robust immunity but raise safety concerns regarding shedding and transmission.
- Intranasal M2SR and BM2SR (M2- and BM2-deficient single replication) influenza viruses are being developed as next-generation vaccines.
- These novel viruses aim for broad cross-reactivity and improved safety profiles.
Purpose of the Study:
- To evaluate the replication deficiency, shedding, and transmissibility of M2SR/BM2SR influenza viruses.
- To assess the reassortment potential of M2SR viruses when coinfected with wild-type influenza.
- To determine the safety and efficacy of these novel vaccine candidates.
Main Methods:
- Ferrets were inoculated with M2SR/BM2SR viruses and monitored for replication, shedding, and transmission.
- Mice were coinfected with wild-type influenza A and M2SR viruses to assess reassortment potential.
- Sequence and PCR analyses were performed on recovered viral genomes.
Main Results:
- M2SR and BM2SR viruses were not detected in ferret tissues or nasal washes and did not transmit to contact animals.
- Coinfection studies in mice showed a low probability of reassortment, with viral genomes exclusively derived from the wild-type virus.
- Absence of shedding was confirmed in a Phase 1 clinical study involving H3N2 M2SR.
Conclusions:
- M2SR/BM2SR influenza vaccine viruses are attenuated, do not shed or transmit, and have a low reassortment risk.
- These findings suggest M2SR/BM2SR viruses have the potential for broader population use compared to current live influenza vaccines.
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