Project description:Twenty adults were randomly assigned to receive either a meningococcal plain-polysaccharide or conjugate vaccine; one month later all received the conjugate vaccine. Blood samples were taken pre-vaccination, and 7, 21, and 28 days after vaccination; B-cell responses were assessed by ELISpot, serum bactericidal assay, flow cytometry and gene expression microarray.
Project description:We performed systems analyses of immune responses to the meningococcal polysaccharide (MPSV4) and conjugate (MCV4) vaccines in healthy adults. The goal was to identify innate gene signatures that correlate to antibody responses induced by these vaccines.
Project description:We performed systems analyses of immune responses to the meningococcal polysaccharide (MPSV4) and conjugate (MCV4) vaccines in healthy adults. The goal was to identify innate gene signatures that correlate to antibody responses induced by these vaccines. Healthy adult volunteers (18-45 years of age) were randomized to be vaccinated subcutaneously with MPSV4 (Menomune®, n=13) or intramuscularly with MCV4 (MenactraTM, n=17) (Sanofi Pasteur, Swiftwater, PA). Whole blood samples were collected using CPT tubes at days 0, 3 and 7 post-vaccination. Peripheral blood mononuclear cells (PBMC) were isolated from fresh blood and used for DNA microarray experiments.
Project description:Group ACYW135 meningococcal polysaccharide vaccine (MPV-ACYW135) is a classical common vaccine used to prevent Neisseria meningitidis serogroup A, C, Y, W135. Although immunological research on MPV has been relatively complete in the past few decades, studies on the vaccine at the transcriptional levels are still limited. In the present study, mRNAs and lncRNAs related to immunity were screened from spleens of mice inoculated with MPV-ACYW135 and compared with the control group to identify the effect and mechanism of these mRNAs and lncRNAs on the immune response. A comprehensive analysis of mRNAs and lncRNAs between MPV group and control group was performed by RNA-seq with bioinformatics.
Project description:To development of our gene expression, we have employed whole rhesus monkey genome microarray expression profiling as a discovery platform to identify genes with the potential to induce immune response. The peripheral blood from rhesus macaques, who were immunized in groups of three with the capsular polysaccharide (CPS antigen), carrier protein tetanus toxoid (TT) or conjugate vaccine via intramuscular injection (i.m.) in the anterolateral thigh on days 0, 30 and 60 using the formulations, were obtained on days 0, 30, 60 and 90. PBMCs were collected for microarray assays. Dynamic expression variations of eight genes (KLRC1, LGALS13, LTB4DH, NUAK1, VNN2, GALNT3, LOC710050 and LOC716305) were maintained in Hib conjugate vaccine group throughout experiment comparing with the CPS antigen group and carrier protein TT group.
Project description:Vaccines to prevent capsular group B meningococcal disease have been based on proteins, as the polysaccharide capsule was deemed unsuitable due to its similarity to human tissues. Outer membrane vesicle (OMV) vaccines have been targeted at specific capsular group B epidemics in Cuba, Norway, and New Zealand, with the major immunogen determined as porin A (PorA). Subcapsular protein vaccines aim to increase breadth of coverage of meningococcal strains, by the inclusion of protein variants from many different clonal complexes (ccs). Using scalable and portable genomic techniques, it is possible to study the diversity of OMV and subcapsular proteins in relevant meningococcal populations. Shotgun proteomics identified 461 proteins in the OMVs derived from NZ98/254, a component of the Bexsero® vaccine, with a complex proteome comprised of outer membrane proteins and proteins from other cellular compartments. Amino acid sequences for 24 selected proteins were catalogued within the PubMLST Neisseria database as part of the OMV peptide Typing (OMVT) scheme. Of the 24 proteins included, there was variation in the extent of diversity and association with ccs from the most conserved peptides FbpA (NEISp0578) and putative periplasmic proteins (NEISp1063) to the most diverse TbpA (NEISp1690). There were 1752 OMVTs identified amongst 2492/3506 isolates. OMVTs were further grouped into clusters (identical at ≥18 peptide sequences), 45.3% of isolates were assigned to one of 27 OMVT clusters. Both OMVTs and clusters were strongly associated with cc, genogroup and recombinant Bexsero® antigens. The OMVT scheme represents an open-access, web-based tool for the systematic analysis of the multiple components of OMV vaccines, demonstrating that combinations of OMV proteins exist in discrete, non-overlapping combinations associated with both genogroup and Bexsero® Antigen Sequence type (BAST). This highly structured population of disease-causing meningococci is consistent with proposed effects of host immune selection and competition between allelic variants on meningococcal population structure. This has implications for future vaccine assessment, and development, especially the choice of antigen combinations. The methodology is portable and will facilitate region-specific WGS interrogation, allowing informed choices about vaccine development or implementation.