Such agents destabilize the outer membrane which enhances
OMVs’ release and preserves the desired biochemical and
immunological properties, even though these OMVs are
not identical to naturally released OMVs (van de Waterbeemd
et al. 2010; Haque and Russell 1974). Van der Ley
et al. (2001) obtained a lpxL1 mutant of N. meningitidis
that retained adjuvant activity similar to wild-type meningococcal
LPS, but has reduced toxicity in vivo. This modified
strain allowed generation of less toxic OMVs. Vaccines
based on OMVs are able to protect against homologous
strains; however, they cannot provide protection against
heterologous strains. The explanation for this lack of a
broad protection is because PorA, the major non-capsular
protective antigen in N. meningitidis OMVs, is highly variable
across different isolates of N. meningitidis. To deal
with this variability, hexavalent and non-hexavalent engineered
vaccines have been developed to over-express different
PorA subtypes (Holst 2007). More recently, other
highly immunogenic antigens have been combined with
OMVs to allow the formulation of a multicomponent vaccine
named 4CMenB (Serruto et al. 2012).
Such agents destabilize the outer membrane which enhancesOMVs’ release and preserves the desired biochemical andimmunological properties, even though these OMVs arenot identical to naturally released OMVs (van de Waterbeemdet al. 2010; Haque and Russell 1974). Van der Leyet al. (2001) obtained a lpxL1 mutant of N. meningitidisthat retained adjuvant activity similar to wild-type meningococcalLPS, but has reduced toxicity in vivo. This modifiedstrain allowed generation of less toxic OMVs. Vaccinesbased on OMVs are able to protect against homologousstrains; however, they cannot provide protection againstheterologous strains. The explanation for this lack of abroad protection is because PorA, the major non-capsularprotective antigen in N. meningitidis OMVs, is highly variableacross different isolates of N. meningitidis. To dealwith this variability, hexavalent and non-hexavalent engineeredvaccines have been developed to over-express differentPorA subtypes (Holst 2007). More recently, otherhighly immunogenic antigens have been combined withOMVs to allow the formulation of a multicomponent vaccinenamed 4CMenB (Serruto et al. 2012).
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