The blue bars denote statistical significance compared with baseline

The blue bars denote statistical significance compared with baseline. we analyzed the kinetics of and associations between IgG, IgA, and IgM B cell responses against recombinant PorA and FetA, including (i) antibody-secreting cells, (ii) memory B cells, and (iii) functional antibody responses (opsonophagocytic and bactericidal activities). Following MenPF1vaccination, PorA-specific IgG secreting cell responses were detected in up to 77% of participants and FetA-specific responses in up to 36%. Memory B cell responses to the vaccine were low or absent and mainly detected in participants who had evidence of preexisting immunity (= 0.0069). Similarly, FetA-specific antibody titers and bactericidal activity increased in participants with preexisting immunity and is consistent with the idea that immune responses are elicited to minor antigens during asymptomatic carriage, which can be boosted by OMV vaccines. IMPORTANCE outer membrane Glycyrrhetinic acid (Enoxolone) vesicles (OMV) are a component of the capsular group B meningococcal vaccine 4CMenB (Bexsero) and have been shown to induce 30% efficacy against gonococcal contamination. They are composed of multiple antigens and are Glycyrrhetinic acid (Enoxolone) considered an interesting delivery platform for vaccines against several bacterial diseases. However, the protective antibody response after two or three doses of OMV-based meningococcal vaccines appears short-lived. We explored the B cell response induced to a dominant and a subdominant antigen in a meningococcal OMV vaccine in a clinical trial and showed that immune responses are elicited Glycyrrhetinic acid (Enoxolone) to minor antigens. However, memory B cell Glycyrrhetinic acid (Enoxolone) responses to the OMV were low or absent and mainly detected in participants who had evidence of preexisting immunity against the antigens. Failure to induce a strong B cell response may be linked with the low persistence of protective responses. KEYWORDS: is usually a Gram-negative diplococcus, which is usually classified into serogroups according to the immunochemistry of the surface polysaccharide capsule with six capsular groups (corresponding to serogroups A, B, C, Glycyrrhetinic acid (Enoxolone) W, Y, and X) responsible for most invasive meningococcal disease (IMD) worldwide (1). Effective conjugate protein-polysaccharide vaccines are available for meningococci expressing capsular groups A, C, W, and Y. However, they have not been developed for capsular group B (MenB) because this polysaccharide is usually poorly immunogenic and is chemically identical to polysialyl decorations of the human neural cell adhesion molecule (NCAM) (2). Therefore, vaccines to target meningococci expressing group B capsule have been developed using subcapsular antigens either as recombinant proteins or outer membrane vesicles (OMVs) (3, 4). Rabbit Polyclonal to APOA5 OMVs are naturally produced by in culture and contain multiple antigens (5, 6), including subcapsular antigens in their natural conformations, such as the immunodominant outer membrane protein (OMP) Porin A (PorA), which is a target for protective antibodies (7). OMV vaccines have been used to control outbreaks of MenB disease caused by a particular hyperinvasive meningococci expressing certain PorA variants (8). However, PorA proteins are highly variable, and OMV vaccines elicit mainly strain-specific protection, especially in children (7). A meningococcal OMV vaccine used in New Zealand (MeNZB) has been shown to induce partial protection against gonococcal contamination, even though gonococcus does not express a PorA protein (9). Consequently, antibody responses elicited to antigens other than PorA (10) may have bactericidal activity against the gonococcus and, potentially, other meningococci (11). Comparative analysis of the predicted surface proteins among 970 gonococcal.