Immunogenicity and Safety of a Multicomponent Meningococcal Serogroup B Vaccine and a Quadrivalent Meningococcal CRM ₁₉₇ Conjugate Vaccine against Serogroups A, C, W-135, and Y in Adults Who Are at Increased Risk for Occupational Exposure to Meningococcal Isolates

Abstract

Laboratory staff who work with meningococcal isolates are at increased risk for developing invasive disease relative to the general population. This was the first study of laboratory workers who received both a conjugate vaccine against meningococcal serogroups A, C, W-135, and Y (Men ACWY-CRM, Menveo) and an investigational multicomponent vaccine against serogroup B containing factor H binding protein, neisserial adhesin A, Neisseria heparin binding antigen, and New Zealand strain outer membrane vesicles (4CMenB). Healthy adults (18 to 50 years of age) received three doses of 4CMenB at baseline, 2 months, and 6 months followed by a single dose of MenACWY-CRM 1 month later. Immunogenicity was assessed via serum bactericidal assay using human complement (hSBA) at 1 month postvaccination; solicited reactogenicity and adverse events were monitored. Fifty-four participants enrolled. Bactericidal immune responses were evident after each dose of 4CMenB, as assessed by hSBA geometric mean titers and percentages of subjects with hSBA titers of >4 against the test strains or a 4-fold rise in titer over baseline. At 1 month postvaccination, most MenACWY-CRM recipients had hSBA titers of >8 against serogroups A, C, W-135, and Y. Few participants discontinued due to an adverse event or vaccine reaction. Rates of solicited reactions were lower after MenACWY-CRM than after 4CMenB administration. Sequential administration of 4CMenB and MenACWY-CRM provided robust evidence of an immune response against serogroups A, B, C, W-135, and Y in laboratory workers routinely exposed to meningococcal isolates.

Immunogenicity and safety of investigational vaccine formulations against meningococcal serogroups A, B, C, W, and Y in healthy adolescents

“…[19][20][21][22] Results from Phase 2 and 3 clinical studies demonstrated that 4CMenB elicited strong bactericidal responses against the vaccine antigens and was generally well tolerated when used in infants and children, adolescents and adults. [21][22][23][24][25][26] 4CMenB has been approved in the EU, Australia, Canada, Chile, and Uruguay for use in individuals beginning from 2 months of age and in the US for use in individuals 10 to 25 y of age.…”

Role of Factor H Binding Protein in Neisseria meningitidis Virulence and Its Potential as a Vaccine Candidate To Broadly Protect against Meningococcal Disease

“…Though there was no statistically significant difference in SBA responses between the two vaccines, a logarithmic regression looked at the effect of the concentration of human factor H on immunogenicity and found that at high fH concentrations, the mutant vaccine generated slightly higher bactericidal responses. Nonetheless, humans vaccinated with wild-type fHBP generate substantial SBA titers (77)(78)(79)(80)(81)(82)(83), demonstrating that this is not a relevant concern for human vaccines. Recently, another meningococcal surface protein, NspA, was found to bind to human fH and contribute to bacterial complement resistance for some MnB strains (45).…”

Neisseria meningitidisB vaccines

“…Sequential administration of 4CMenB and Menveo ® provided robust evidence of an immune response against all serogroups. Both vaccines were well tolerated [97]. The percentage of infants with hSBA titers of 1:4 or higher against reference strains were 100, 98 and 93% after the booster dose [93] 5CVMB (rMenB) + OMV strain NZ98/254…”