Isaac G Sakala1, Yoshikazu Honda-Okubo1, Lei Li1, Jeremy Baldwin2, Nikolai Petrovsky3. 1. Vaxine Pty Ltd, 11 Walkley Avenue, Adelaide 5046, Australia; College of Medicine and Public Health, Flinders University, Adelaide 5042, Australia. 2. Vaxine Pty Ltd, 11 Walkley Avenue, Adelaide 5046, Australia. 3. Vaxine Pty Ltd, 11 Walkley Avenue, Adelaide 5046, Australia; College of Medicine and Public Health, Flinders University, Adelaide 5042, Australia. Electronic address: nikolai.petrovsky@flinders.edu.au.
Abstract
BACKGROUND: Despite newborns being at increased risk of serious influenza infection, influenza vaccines are currently not recommended for use in infants under 6 months of age. We therefore sought to evaluate the protective efficacy in mice of an M2-based influenza vaccine (CapM2e) formulated with Advax-SM adjuvant. Vaccine protection was assessed via both passive maternal immunization and direct neonatal immunization. METHODS: For maternal transfer studies, female mice were immunized 1 week before and after mating. Blood was collected from both mother and offspring during weaning and pups were challenged when they reached 3 weeks of age with lethal doses of H1N1 and homologous reassortment influenza strain H3N2 with conserved M2. For direct immunization studies, newborns were immunized at 1 and 3 weeks of age and blood was collected prior to challenge at 4 weeks of age. RESULTS: Maternal immunization with CapM2e + Advax-SM vaccine induced high maternal M2e antibody levels that were passively transferred to their offspring and provided them with protection against both H1N1 and H3N2 influenza strains when challenged at 3 weeks of age. When used for direct immunization of neonatal mice, CapM2e + Advax-SM vaccine similarly induced high serum M2e antibody levels and protected against H1N1 and H3N2 influenza challenges with protection associated with inhibition of virus replication with a significant reduction in lung virus load in immunized pups. CONCLUSION: CapM2e + Advax-SM vaccine could be useful for protecting newborns against diverse influenza A strains, with opportunities to achieve protection by passive maternal immunization or active neonatal immunization. This data supports further development of this promising M2e-based vaccine candidate.
BACKGROUND: Despite newborns being at increased risk of serious influenza infection, influenza vaccines are currently not recommended for use in infants under 6 months of age. We therefore sought to evaluate the protective efficacy in mice of an M2-based influenza vaccine (CapM2e) formulated with Advax-SM adjuvant. Vaccine protection was assessed via both passive maternal immunization and direct neonatal immunization. METHODS: For maternal transfer studies, female mice were immunized 1 week before and after mating. Blood was collected from both mother and offspring during weaning and pups were challenged when they reached 3 weeks of age with lethal doses of H1N1 and homologous reassortment influenza strain H3N2 with conserved M2. For direct immunization studies, newborns were immunized at 1 and 3 weeks of age and blood was collected prior to challenge at 4 weeks of age. RESULTS: Maternal immunization with CapM2e + Advax-SM vaccine induced high maternal M2e antibody levels that were passively transferred to their offspring and provided them with protection against both H1N1 and H3N2 influenza strains when challenged at 3 weeks of age. When used for direct immunization of neonatal mice, CapM2e + Advax-SM vaccine similarly induced high serum M2e antibody levels and protected against H1N1 and H3N2 influenza challenges with protection associated with inhibition of virus replication with a significant reduction in lung virus load in immunized pups. CONCLUSION: CapM2e + Advax-SM vaccine could be useful for protecting newborns against diverse influenza A strains, with opportunities to achieve protection by passive maternal immunization or active neonatal immunization. This data supports further development of this promising M2e-based vaccine candidate.
Authors: Lei Li; Yoshikazu Honda-Okubo; Jeremy Baldwin; Richard Bowen; Helle Bielefeldt-Ohmann; Nikolai Petrovsky Journal: Vaccine Date: 2022-04-18 Impact factor: 4.169