Naturally Acquired Passive Protective Activity against Neisseria meningitidis Group C in the Absence of Serum Bactericidal Activity

Abstract

The hallmark of immunity to meningococcal disease is a bactericidal titer in serum of >1:4 measured with human complement, but this threshold titer may underestimate the extent of protection. We used the infant rat model of meningococcal bacteremia to measure group C passive protective activity in serum samples from 91 unimmunized adults living in California. A total of 35 sera (38.5%) had passive protective activity. Sera with complement-mediated bactericidal titers of >1:4 were 3.4-fold more likely to confer protection (89%) than nonbactericidal sera (26%; P < 0.0001). Thus, bactericidal titers of >1:4 are a marker of protection, but this threshold lacks sensitivity for predicting protective activity. We investigated the 73 sera with bactericidal titers of <1:4 to determine the basis of protective activity. The 19 sera with protective activity had a higher geometric mean group C anticapsular antibody concentration (0.72 g/ml) than the 54 sera that lacked protective activity (0.16 g/ml; P < 0.001). Thus, protective activity in the absence of bactericidal activity was associated with higher concentrations of anticapsular antibodies, but not all sera with anticapsular antibodies conferred protection. Of 18 nonbactericidal sera with anticapsular antibody concentrations between 0.31 and 0.99 g/ml, the 11 sera that conferred protection had a higher mean antibody avidity constant (21.9 nM ؊1 ) than the 7 nonprotective sera (14.6 nM ؊1 ; P < 0.03). Thus, in sera with titers of <1:4, protective activity is associated with higher-avidity group C anticapsular antibodies, which are present in concentrations insufficient to elicit complement-mediated bacteriolysis in vitro but sufficient to confer protection in an in vivo bacteremia model.

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

“…meningococcal ACWY-TT vaccine (Nimenrix Ò ), with only 20.6% of healthy toddlers 12 months of age retaining hSBA antibody titers 4 against serogroup A at 1 y after vaccination 33 and only 21.8% of healthy toddlers 12-23 months of age retaining hSBA antibody titers against serogroup A at 3 y after vaccination. 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.…”

Porin A—Specific Antibody Avidity in Patients Who Are Convalescing from Meningococcal B Disease

“…Opsonic activity was found in patients after meningococcal serogroup B infection (19). Also, animal studies have shown that protective activity was associated with high-avidity antibodies (18,20,21). The PorA-specific avidity induced after infection therefore may play an import role in protection.…”

“…Other mechanisms therefore may be responsible for induced protection after infection. Recently, several studies have shown protection in infant rat models against meningococcal infection in absence of SBA activity (17,18). The most likely mechanism responsible for protective activity in the absence of SBA is opsonization.…”

Contrasting B cell- and T cell-based protective vaccines

“…One study indicates that in individuals who had a severe exposure to rabies virus a single booster inoculation 4 years after the initial (post-exposure) treatment was sufficient to maintain a rabies specific antibody titer that would probably confer protection against a second exposure (Fayaz et al, 1981). In another study a threshold titer (with human complement) was found that was likely to confer protection to meningococcal disease (Welsch and Granoff, 2004). In this study protection in the absence of bactericidal activity by complement was associated with significantly higher concentrations and avidities of antibodies directed against a capsular protein of the meningococcus.…”