A native outer membrane vesicle vaccine confers protection against meningococcal colonization in human CEACAM1 transgenic mice

Abstract

Background The effect of protein-based meningococcal vaccines on prevention of nasopharyngeal colonization has been difficult to investigate experimentally because a reliable animal colonization model did not exist. Methods Human CEACAM1 transgenic mice, which can be colonized by meningococci, were immunized IP with one of two meningococcal native outer membrane vesicle (NOMV) vaccines prepared from mutants with attenuated endotoxin (lpxL1 knockout) and over-expressed sub-family B Factor H-binding proteins (FHbp). Animals were challenged intranasally two weeks after the third dose with wild-type strain H44/76, or were treated IP with anti-NOMV serum before and during the bacterial challenge. Results The NOMV-1 vaccine, prepared from the serogroup B H44/76 mutant, elicited ~40-fold higher serum bactericidal antibody titers against the wild-type H44/76 challenge strain than the NOMV-2 vaccine prepared from a heterologous serogroup W mutant strain with different PorA and FHbp amino acid sequence variants. Compared to aluminum hydroxide-immunized control mice, the efficacy for prevention of any H44/76 colonization was 93% (95% confidence interval, 52-99, P<0.0001) for the NOMV-1 vaccine, and 19% (−3-36, P=0.23) for NOMV-2. NOMV-2-vaccinated mice had a 5.6-fold decrease in geometric mean CFU of bacteria per animal in tracheal washes compared to control mice (P=0.007). The efficacy of passive administration of serum from NOMV-1-vaccinated mice to immunologically naïve mice against colonization was 44% (17-61; P=0.002). Conclusions Both NOMV vaccines protected against meningococcal colonization but there was greater protection by the NOMV-1 vaccine with antigens matched with the challenge strain. Meningococcal vaccines that target protein antigens have potential to decrease colonization.

<p>Chimeric hepatitis B virus core particles displaying Neisserial surface protein A confer protection against virulent <em>Neisseria meningitidis</em> serogroup B in BALB/c mice</p>

“…These results provide a foundation for further investigation of the Th2 immune response, as it is established that this response is crucial for SBA in vitro 33. The SBA is the current gold standard for determining resistance after VLP vaccination, and the serum bacterial killing titer of HBc-N144-NspA mixed with Freund’s adjuvant reached 1:16, proving that the immunized mice generated potent-specific antibodies, while vaccination with HBc-N144-NspA in the absence of adjuvant also generated SBA of approximately 1:8, mediated by human serum complement, which far exceeds the results reported from the previous Phase I clinical trial 34. Although the immune responses elicited by VLPs are weaker than those induced by the four-component vaccine, the purpose of this study was to screen for novel suitable vectors and potential antigens for the development of a new generation vaccine after structural modification.…”

A meningococcal NOMV-FHbp vaccine for Africa elicits broader serum bactericidal antibody responses against serogroup B and non-B strains than a licensed serogroup B vaccine

“…However, as shown in the present study, NOMV-FHbp vaccines have the potential to elicit higher serum bactericidal response than MenB-4C, which also might translate into a greater effect on decreasing colonization. In a human CEACAM1 transgenic mouse model, an investigational NOMV-FHbp vaccine decreased meningococcal colonization [37]. A third possible disadvantage of protein-based vaccines is that antigens might drive immune selection for resistant strains (from antigenic drift, or loss of antigen expression from frameshift mutations or deletion of genes) [38].…”

Persistence of the immune response after MenACWY-CRM vaccination and response to a booster dose, in adolescents, children and infants

“…34 Laboratory and assay considerations in assessment of persistence against serogroup A Antibody decay rates also depend on the serological assay used for measurement of antibody titers. Several types of serological assays have historically been used for assessment of meningococcal antigen-specific immunity, including assays that measure complement-mediated bacterial killing using endogenous and exogenous complement (rabbit or human), anti-capsular antibody levels, or opsonophagocytosis, 35 and assays using different animal protection models.…”