The bacterium Neisseria meningitidis of serogroups A and W‐135 has in the recent decade caused most of the cases of meningococcal meningitis in the African meningitis belt, and there is currently no efficient and affordable vaccine available demonstrated to protect against both these serogroups. Previously, deoxycholate‐extracted outer membrane vesicle (OMV) vaccines against serogroup B meningococci have been shown to be safe and induce protection in humans in clonal outbreaks. The serogroup A and W‐135 strains isolated from meningitis belt epidemics demonstrate strikingly limited variation in major surface‐exposed protein structures. We have here investigated whether the OMV vaccine strategy also can be applied to prevent both serogroups A and W‐135 meningococcal disease. A novel vaccine combining OMV extracted from recent African serogroup A and W‐135 strains and adsorbed to aluminium hydroxide was developed and its antigenic characteristics and immunogenicity were studied in mice. The specificity of the antibody responses was analysed by immunoblotting and serum bactericidal activity (SBA) assays. Moreover, the bivalent A+W‐135 vaccine was compared with monovalent A and W‐135 OMV vaccines. The bivalent OMV vaccine was able to induce similar SBA titres as the monovalent A or W‐135 OMV towards both serogroups. High SBA titres were also observed against a meningococcal serogroup C strain. These results show that subcapsular antigens may be of importance when developing broadly protective and affordable vaccines for the meningitis belt.

Previous reports demonstrated that FLU-v, a peptide-based broad-spectrum influenza vaccine candidate, induced antibody and cellular immune responses in humans. Here, we evaluate cellular effector functions and cross-reactivity. PBMC sampled pre- (day 0) and post-vaccination (days 42 and 180) from vaccine (n = 58) and placebo (n = 27) recipients were tested in vitro for responses to FLU-v and inactivated influenza strains (A/H3N2, A/H1N1, A/H5N1, A/H7N9, B/Yamagata) using IFN-γ and granzyme B ELISpot. FLU-v induced a significant increase in the number of IFN-γ- and granzyme-B-secreting cells responding to the vaccine antigens from pre-vaccination (medians: 5 SFU/10⁶ cells for both markers) to day 42 (125 and 40 SFU/10⁶ cells, p < 0.0001 for both) and day 180 (75 and 20 SFU/10⁶ cells, p < 0.0001 and p = 0.0047). The fold increase from pre-vaccination to day 42 for IFN-γ-, granzyme-B-, and double-positive-secreting cells responding to FLU-v was significantly elevated compared to placebo (medians: 16.3-fold vs. 1.0-fold, p < 0.0001; 3.5-fold vs. 1.0-fold, p < 0.0001; 3.0-fold vs. 1.0-fold, p = 0.0012, respectively). Stimulation of PBMC with inactivated influenza strains showed significantly higher fold increases from pre-vaccination to day 42 in the vaccine group compared to placebo for IFN-γ-secreting cells reacting to H1N1 (medians: 2.3-fold vs. 0.8-fold, p = 0.0083), H3N2 (1.7-fold vs. 0.8-fold, p = 0.0178), and H5N1 (1.7-fold vs. 1.0-fold, p = 0.0441); for granzyme B secreting cells reacting to H1N1 (3.5-fold vs. 1.0-fold, p = 0.0075); and for double positive cells reacting to H1N1 (2.9-fold vs. 1.0-fold, p = 0.0219), H3N2 (1.7-fold vs. 0.9-fold, p = 0.0136), and the B strain (2.0-fold vs. 0.8-fold, p = 0.0227). The correlation observed between number of cells secreting IFN-γ or granzyme B in response to FLU-v and to the influenza strains supported vaccine-induced cross-reactivity. In conclusion, adjuvanted FLU-v vaccination induced cross-reactive cellular responses with cytotoxic capacity, further supporting the development of FLU-v as a broad-spectrum influenza vaccine.

We developed and evaluated a rapid and simple multiplex microsphere assay for the quantification of specific IgG and IgA antibodies against meningococcal serogroup A, C, W, and Y capsular polysaccharides in serum and saliva. Meningococcal polysaccharides were conjugated to distinct magnetic carboxylated microspheres, and the performance of the assay was assessed using the CDC1992 standard meningococcal reference serum and a panel of serum and saliva samples. The standard curve was linear over an eight 3-fold dilution range in the IgG assay and a seven 3-fold dilution range in the IgA assay. No cross-reactivity was discovered, and the assay showed high specificity with ≥91% homologous inhibition and ≤11% heterologous inhibition for all serogroups and immunoglobulin classes. Lower limits of detections were ≤280 pg/ml for IgG and ≤920 pg/ml for IgA antibodies. The assay was reproducible, with a mean coefficient of variation of ≤5% for intra-assay duplicates, a mean coefficient of variation of ≤20% for interassay repeated analysis with different conjugations of microspheres, and a mean coefficient of variation within 25.8% for interoperator variation. The assay showed good correlation to the standard meningococcal polysaccharide enzyme-linked immunosorbent assay (ELISA) for detection of serum antibodies. This multiplex assay is robust and reliable and requires less sample volume, and less time and workload are needed than for ELISA, making this method highly relevant for serological and salivary investigations on the effect of meningococcal vaccines and for immunosurveillance studies.

Background/Objectives: FLU-v is a peptide-based broad-spectrum influenza vaccine proven to induce humoral and cellular immune responses in humans. In this study, FLU-v-specific IgG1 and IgG3 subclass antibodies, induced by adjuvanted or non-adjuvanted FLU-v vaccination in healthy adults participating in a phase II clinical study, were quantitated. The ability of these antibodies to induce NK cell activation was investigated. Methods: An ELISA was developed to quantify FLU-v-specific IgG1 and IgG3 antibodies in serum. A flowcytometric assay based on an NK cell line was used to evaluate NK cell activation by expression of degranulation marker CD107a. Results: In the adjuvanted FLU-v group, IgG1 and IgG3 seroconversion on day 42 was 88.5% and 86.5% compared to 53.4% and 29.3% in the non-adjuvanted FLU-v group, which was significantly different from the respective placebo groups (0–6.3%). Adjuvanted FLU-v vaccination induced a raise in median IgG1 and IgG3 levels from 435 and 167 ng/mL pre vaccination to 4422 and 2020 ng/mL 42 days post vaccination, representing a fold increase of 16.3 for IgG1 and 11.6 for IgG3, which was sustained on day 180 post vaccination (10.4-fold and 5.0-fold, respectively). Non-adjuvanted vaccination induced a more modest increase in IgG1 and IgG3 from 655 and 206 ng/mL pre vaccination to 1808 and 264 ng/mL 42 days post vaccination. A correlation between levels of FLU-v-specific IgG, IgG1, or IgG3 and their ability to induce NK cell activation was demonstrated. Conclusions: A single dose of adjuvanted FLU-v induced high levels of long-lasting antigen-specific IgG1 and IgG3 antibodies with NK cell-mediated effector functions relevant to protection against influenza disease.

Background: As one of few countries in Europe, Norway does not offer vaccination against invasive meningococcal disease (IMD) as part of the National Immunization Program for Children (NIP). Instead, adolescents aged 16–19 are recommended to consider having the meningococcal ACWY conjugate vaccine (MCV4) if they participate in activities that increase the risk of IMD. Meningococcal vaccination rates in Norway are low compared to vaccines offered through the NIP. Whereas all vaccinations in the NIP are free and organized through schools or municipal health clinics, there is no uniform system in place for the meningococcal vaccine. On the contrary, both administration practices and cost of vaccination vary nationally, with some counties offering the vaccine for free, while others offer the vaccine at a cost of $40–80. The aim of this study was to explore adolescents’ awareness, knowledge, and decision-making processes related to meningococcal disease and vaccination. Methods: Using a semi-structured interview guide, we conducted 18 focus group interviews in the fall of 2022, involving a total of 126 high school seniors in Norway. The participants were asked to share their views, knowledge and experiences regarding invasive meningococcal disease and vaccination. We used NVivo 14 to facilitate the thematic analysis and a codebook analysis approach was conducted to identify themes and patterns in the data. Results: The analysis identified three central themes emerging from the discussions with the adolescents. These emphasize how information, cost, and location and guidance impact the adolescents’ decision-making and ability to get vaccinated. Conclusions: The current organization of MCV4 vaccination in Norway do not meet the needs identified by the adolescents in this study. This results in unequal access to a highly effective vaccine that protects healthy adolescents against a deadly disease. The present study highlights the need to address vaccination disparities and accessibility, as well as increasing awareness and knowledge about meningococcal disease and vaccination to ensure equal access for all adolescents.