Persisting Immune Responses Indicating Long-Term Protection after Booster Dose with Meningococcal Group B Outer Membrane Vesicle Vaccine

Abstract

MenBvac is an outer membrane vesicle vaccine against systemic meningococcal disease caused by serogroup B Neisseria meningitidis. In this placebo-controlled double-blind study including 374 healthy adolescents, the safety and immunogenicity of a schedule of three primary doses 6 weeks apart followed by a fourth dose a year later were evaluated. Antibody responses to the vaccine strain and heterologous strains (non-vaccine-type strains) and the persistence of these antibodies were measured by the serum bactericidal assay (SBA) and enzyme-linked immunosorbent assay up to 1 year after the last dose. The proportion of subjects with SBA titers of >4 against the vaccine strain increased from 3% prevaccination to 65% after the third dose. Ten months later, this proportion had declined to 28%. The fourth dose induced a booster response demonstrated by 93% of subjects achieving a titer of >4. One year after the booster dose, 64% still showed SBA titers of >4. Cross-reacting antibodies were induced against all heterologous strains tested, although the magnitude of SBA titers differed widely between the different strains. All four doses of MenBvac were safe. Both MenBvac and the placebo had reactogenicity profiles of mild to moderate local and systemic reactions. Pain, the most common reaction, was reported with similar frequencies in both groups. No serious adverse events occurred in the MenBvac group. This study confirmed the good immunogenicity of the primary course of MenBvac and demonstrated prolonged persistence and increased cross-reactivity of functional antibodies elicited by a booster dose.

Immunogenicity, Reactogenicity, and Safety of a P1.7b,4 Strain-Specific Serogroup B Meningococcal Vaccine Given to Preteens

“…Bactericidal antibody activity decay has been seen after two, three, and four doses of the MenBvac Norwegian parent vaccine (11,18). MenBvac has been shown to elicit fourfold rises in serum bactericidal antibody titer in 61% of adolescents after three doses and in 90% after a fourth dose 1 year later (11).…”

Naturally Produced Outer Membrane Vesicles fromPseudomonas aeruginosaElicit a Potent Innate Immune Response via Combined Sensing of Both Lipopolysaccharide and Protein Components

“…Notably, a protective antibody response is elicited by outer membrane vesicles generated from Neisseria meningitidis and Vibrio cholerae (17,18,38,40,47). In contrast, there are relatively few studies characterizing how vesicles trigger the innate inflammatory response.…”

Delivery of foreign antigens by engineered outer membrane vesicle vaccines

“…In contrast to synthetic particulate systems, these OMV vaccines represent a unique system where the antigen and delivery vehicle together are derived from the Neisseria meningitidis pathogen itself (15,16). The proven safety and efficacy records of these OMV vaccines, particularly in The Netherlands (17) and in Norway (12,18), together with the knowledge that vesicles are produced by nearly all species of Gram-negative bacteria (including Escherichia coli), present the possibility of employing OMVs for the delivery of recombinant protein antigens. To date, however, antigens that are foreign to the parental bacteria remain notably absent from OMVs largely because of challenges associated with the transport of heterologous proteins to the vesicles (19).…”

“…There are currently two vaccines for serogroup B meningococcal disease that are formulations consisting of bacterial surface antigens naturally incorporated in outer membrane vesicles (OMVs) (11,12). OMVs are nanoscale (∼100 nm) proteoliposomes that constitutively bud from the outer membrane of Gram-negative bacteria (13,14), and they contain components derived from the bacterial outer membrane and periplasm.…”