Project description:In this study, we describe the development and use of an ad hoc protein microarray to study the immune response induced by the three major 4CMenB antigenic components (fHbp, NHBA and NadA) in individual sera from vaccinated infants, adolescents and adults.
Project description:Serogroup B meningococcus (MenB) is a leading cause of meningitis and sepsis across the world and vaccination is the most effective way to protect against this disease. 4CMenB is a multi-component vaccine against MenB, which is now licensed for use in subjects >2 months of age in several countries. In this study, we describe the development and use of an ad hoc protein microarray to study the immune response induced by the three major 4CMenB antigenic components (fHbp, NHBA and NadA) in individual sera from vaccinated infants, adolescents and adults. The resulting 4CMenB protein antigen fingerprinting allowed the identification of specific human antibody repertoire correlating with the bactericidal response elicited in each subject. This work represents an example of epitope mapping of the immune response induced by a multicomponent vaccine in different age groups with the identification of protective signatures. It shows the high flexibility of this microarray based methodology in terms of high-throughput information and minimal volume of biological samples needed.
Project description:In this study, we describe the development and use of an ad hoc protein microarray to study the immune response induced by the OMV component of 4CMenB vaccine in infant sera before and after vaccination
Project description:In this study, we describe the development and use of an ad hoc protein microarray to study the immune response induced by the OMV component of 4CMenB vaccine in mouse sera before and after immunization.
Project description:Development of a vaccine against gonorrhoea is a global priority, driven by the rise in antibiotic resistance and the need to protect against infection and reproductive health consequences. Although Neisseria gonorrhoeae (Ng) infection does not induce substantial protective immunity, there is evidence that highly exposed individuals may develop immunity against re-infection with the same strain. In contrast, retrospective epidemiological studies have shown that immunisation with vaccines containing Neisseria meningitidis (Nm) outer membrane vesicles (OMVs) provides a degree of cross-protection against Ng infection. To examine this phenomenon, we conducted a clinical trial of 4CMenB (Bexsero®, GSK), a licensed vaccine against Nm that contains OMVs and recombinant antigens, with 50 adults in coastal Kenya who have high exposure to Ng. The study comprised a single arm open label study of two doses of Bexsero; humoral and cellular immune responses were measured at three time points over six months. Using a dedicated microarray of Ng antigens, we show that serum IgG and IgA reactivities against the gonococcal homologs of the recombinant antigens in the vaccine peaked at 10 weeks but had declined by 24 weeks. The reverse was the case for most antigens originating from the OMV component. A cohort of similar individuals with laboratory-confirmed gonococcal infection were compared before, during, and after infection: their reactivities were weaker and differed from the vaccinated cohort. We conclude that the cross-protection of the 4CMenB vaccine against gonorrhoea could be explained by cross-reaction against a diverse selection of antigens derived from the OMV component.
Project description:We report a first-in-human trial evaluating safety and immunogenicity of a recombinant BCG, AERAS-422, over-expressing TB antigens Ag85A, Ag85B, and Rv3407 and expressing mutant perfringolysin. Interpretation: The unexpected development of VZV in two of eight healthy adult vaccine recipients resulted in discontinuation of AERAS-422 vaccine development. Immunological and transcriptomal data identified correlations with the development of TB immunity and VZV that require further investigation.
Project description:Neisseria meningitidis is a major cause of endemic cases and epidemics of meningitis and devastating septicemia. Although effective vaccines exist for several serogroups of pathogenic N. meningitidis, conventional vaccinology approaches have failed to provide a universal solution for serogroup B (MenB) which consequently remains an important burden of disease worldwide. The advent of whole-genome sequencing changed the approach to vaccine development, enabling the identification of potential vaccine candidates starting directly with the genomic information, with a process named reverse vaccinology. The application of reverse vaccinology to MenB allowed the identification of new protein antigens able to induce bactericidal antibodies. Three highly immunogenic antigens (fHbp, NadA and NHBA) were combined with outer membrane vesicles and formulated for human use in a multicomponent vaccine, named 4CMenB. This is the first MenB vaccine based on recombinant proteins able to elicit a robust bactericidal immune response in adults, adolescents and infants against a broad range of serogroup B isolates. This review describes the successful story of the development of the 4CMenB vaccine, with particular emphasis on the functional, immunological and structural characterization of the protein antigens included in the vaccine.