BACKGROUND: An improved nonavalent PorA native outer membrane vesicle vaccine was developed with intrinsic adjuvating activity due to presence of less-toxic (lpxL1) LPS. In the present study, the safety and immunogenicity of this next-generation NonaMen vaccine were evaluated following repeated vaccination in rabbits and mice. METHODS: A repeated-dose toxicology study was performed in rabbits. Immunogenicity of next-generation NonaMen was evaluated by determining the serum bactericidal antibody (SBA) titers against meningococcal serogroup B strains containing several PorA subtypes. Release of the pro-inflammatory cytokine, interleukin-6 (IL-6), by the human monocytic cell line (MM6) was measured to estimate pyrogenic activity. RESULTS: No toxicologically relevant findings were noted in vaccinated rabbits receiving plain next-generation NonaMen. In agreement, next-generation NonaMen induced reduced amounts of the pro-inflammatory cytokine, IL-6, released by human monocyte cell line. In both rabbits and mice, next-generation NonaMen induced high SBA titers against all tested MenB strains regardless of whether or not aluminium phosphate adjuvant is used. CONCLUSIONS: The data suggest that next-generation NonaMen is a safe vaccine with the potential to develop a broadly protective immune response and encourage the start of the first clinical studies.
BACKGROUND: An improved nonavalent PorA native outer membrane vesicle vaccine was developed with intrinsic adjuvating activity due to presence of less-toxic (lpxL1) LPS. In the present study, the safety and immunogenicity of this next-generation NonaMen vaccine were evaluated following repeated vaccination in rabbits and mice. METHODS: A repeated-dose toxicology study was performed in rabbits. Immunogenicity of next-generation NonaMen was evaluated by determining the serum bactericidal antibody (SBA) titers against meningococcal serogroup B strains containing several PorA subtypes. Release of the pro-inflammatory cytokine, interleukin-6 (IL-6), by the human monocytic cell line (MM6) was measured to estimate pyrogenic activity. RESULTS: No toxicologically relevant findings were noted in vaccinated rabbits receiving plain next-generation NonaMen. In agreement, next-generation NonaMen induced reduced amounts of the pro-inflammatory cytokine, IL-6, released by human monocyte cell line. In both rabbits and mice, next-generation NonaMen induced high SBA titers against all tested MenB strains regardless of whether or not aluminium phosphate adjuvant is used. CONCLUSIONS: The data suggest that next-generation NonaMen is a safe vaccine with the potential to develop a broadly protective immune response and encourage the start of the first clinical studies.
Authors: Jay Lucidarme; Stefanie Gilchrist; Lynne S Newbold; Stephen J Gray; Edward B Kaczmarski; Lynne Richardson; Julia S Bennett; Martin C J Maiden; Jamie Findlow; Ray Borrow Journal: Clin Vaccine Immunol Date: 2013-06-26
Authors: Bas van de Waterbeemd; Gijsbert Zomer; Patricia Kaaijk; Nicole Ruiterkamp; René H Wijffels; Germie P J M van den Dobbelsteen; Leo A van der Pol Journal: PLoS One Date: 2013-05-31 Impact factor: 3.240
Authors: Abel E Vasquez; Ricardo A Manzo; Daniel A Soto; Magaly J Barrientos; Aurora E Maldonado; Macarena Mosqueira; Anastasia Avila; Jorge Touma; Elsa Bruce; Paul R Harris; Alejandro Venegas Journal: Hum Vaccin Immunother Date: 2015 Impact factor: 3.452
Authors: Jamie Findlow; Christopher D Bayliss; Peter T Beernink; Ray Borrow; Paul Liberator; Paul Balmer Journal: Vaccine Date: 2020-08-30 Impact factor: 3.641