Intranasal M2SR and BM2SR Vaccine Viruses Do Not Shed or Transmit in Ferrets

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.