BACKGROUND: The effectiveness of antibiotics for treating gonococcal infections is compromised due to escalating antibiotic resistance; and the development of an effective gonococcal vaccine has been challenging. Emerging evidence suggests that the licensed meningococcal B (MenB) vaccine, 4CMenB is effective against gonococcal infections due to cross-reacting antibodies and 95% genetic homology between the two bacteria, Neisseria meningitidis and Neisseria gonorrhoeae, that cause the diseases. This project aims to undertake epidemiological and genomic surveillance to evaluate the long-term protection of the 4CMenB vaccine against gonococcal infections in the Northern Territory (NT) and South Australia (SA), and to determine the potential benefit of a booster vaccine doses to provide longer-term protection against gonococcal infections.
METHODS: This observational study will provide long-term evaluation results of the effectiveness of the 4CMenB vaccine against gonococcal infections at 4-7 years post 4CMenB programme implementation. Routine notifiable disease notifications will be the basis for assessing the impact of the vaccine on gonococcal infections. Pathology laboratories will provide data on the number and percentage of N. gonorrhoeae positive tests relative to all tests administered and will coordinate molecular sequencing for isolates. Genome sequencing results will be provided by SA Pathology and Territory Pathology/New South Wales Health Pathology, and linked with notification data by SA Health and NT Health. There are limitations in observational studies including the potential for confounding. Confounders will be analysed separately for each outcome/comparison.
BACKGROUND: The protocol and all study documents have been reviewed and approved by the SA Department for Health and Well-being Human Research Ethics Committee (HREC/2022/HRE00308), and the evaluation will commence in the NT on receipt of approval from the NT Health and Menzies School of Health Research Human Research Ethics Committee. Results will be published in peer-reviewed journals and presented at scientific meetings and public forums.

BACKGROUND: Gonorrhoea, the sexually transmissible infection caused by Neisseria gonorrhoeae, has a substantial impact on sexual and reproductive health globally with an estimated 82 million new infections each year worldwide. N. gonorrhoeae antimicrobial resistance continues to escalate, and disease control is largely reliant on effective therapy as there is no proven effective gonococcal vaccine available. However, there is increasing evidence from observational cohort studies that the serogroup B meningococcal vaccine four-component meningitis B vaccine (4CMenB) (Bexsero), licensed to prevent invasive disease caused by Neisseria meningitidis, may provide cross-protection against the closely related bacterium N. gonorrhoeae. This study will evaluate the efficacy of 4CMenB against N. gonorrhoeae infection in men (cis and trans), transwomen and non-binary people who have sex with men (hereafter referred to as GBM+).
METHODS: This is a double-blind, randomised placebo-controlled trial in GBM+, either HIV-negative on pre-exposure prophylaxis against HIV or living with HIV (CD4 count >350 cells/mm3), who have had a diagnosis of gonorrhoea or infectious syphilis in the last 18 months (a key characteristic associated with a high risk of N. gonorrhoeae infection). Participants are randomised 1:1 to receive two doses of 4CMenB or placebo 3 months apart. Participants have 3-monthly visits over 24 months, which include testing for N. gonorrhoeae and other sexually transmissible infections, collection of demographics, sexual behaviour risks and antibiotic use, and collection of research samples for analysis of N. gonorrhoeae-specific systemic and mucosal immune responses. The primary outcome is the incidence of the first episode of N. gonorrhoeae infection, as determined by nucleic acid amplification tests, post month 4. Additional outcomes consider the incidence of symptomatic or asymptomatic N. gonorrhoeae infection at different anatomical sites (ie, urogenital, anorectum or oropharynx), incidence by N. gonorrhoeae genotype and antimicrobial resistance phenotype, and level and functional activity of N. gonorrhoeae-specific antibodies.
BACKGROUND: Ethical approval was obtained from the St Vincent\'s Hospital Human Research Ethics Committee, St Vincent\'s Hospital Sydney, NSW, Australia (ref: 2020/ETH01084). Results will be disseminated in peer-reviewed journals and via presentation at national and international conferences.
BACKGROUND: NCT04415424.

In the present study the compositional analysis of the amino acids released by the acidic hydrolysis of the vaccine antigens was approached as an alternative to the dye-binding methods, for improvement of the quality control. In particular, the Analytical Quality by Design principles were undertaken in optimizing the hydrolysis conditions of the antigens to be applied prior to the quantitation by UHPLC-UV. Bexsero was used as a case study; it is a recombinant meningococcal B vaccine and one of its critical quality attributes is the content of the three core protein antigens, namely Neisseria Heparin Binding Antigen, factor H binding protein and Neisseria adhesin A, in the final formulation. Conventionally, the proteins quantitation is carried out by dye-binding assays. Analytical Target Profile was defined as the accurate determination of amounts of the Bexsero antigens. The Critical Method Parameters were chosen by means of the cause-effect matrix. A Face Centered Design was used to select the experiments to investigate the process and finally a Method Operable Design Region with a risk of failure of 5% was defined. The selected working point for routine use was: hydrolysis time, 17 hrs; temperature, 112 °C; 6 M HCl volume, 300 µl; antioxidant 90% phenol volume, 5 µl.

In Italy Rotavirus vaccination (RVV) is provided free of charge from 2018, however, the coverage is scattered and suboptimal. The narrow time frame to complete the schedule is a barrier to uptake, and co-administration with other vaccines may potentially increase the coverage. Although the co-administration of RV vaccine and Meningococcal Group B vaccine (MenB) is not included in the product labels, we aimed at studying its impact on RVV coverage.
This Surveillance study on Timing and cOverage of Rotavirus and MenB vaccine co-administration (STORM study) used the Regional Vaccination Registry to collect data about children born in Campania Region between January 2016 and December 2020, and receiving vaccines scheduled in the first year of life.
Among the 224,110 children enrolled, 60,614 (27.0%) completed the RVV schedule, with a vaccination rate that increased over time from 1.15% in 2016 to 56.92% in 2020. The first and last dose of RVV schedule were administered beyond the recommended time in 6% of the study population, respectively. Co-administration of RV vaccine with MenB vaccine increased from 0.7 % in 2016 to 46.85 % in 2020. Children receiving RV/MenB vaccines concomitantly had a significantly higher chance of completing the RV schedule compared to those receiving RVV alone during a specific appointment (94.78 % vs 72.26 %, Prevalence Ratio -PR- 1.275, 95 %CI 1.245-1.295p < 0.00001). The positive driving effect of RV/MenB co-administration was more evident for children receiving pentavalent (PR 1.288) than monovalent RVV (PR 1.115) which was confirmed when adjusted for confounding variables (i.e., year of vaccination, local district, gender).
Although still far from the target, RVV coverage has increased in recent years in Campania Region. Co-administration with MenB vaccine may aid in increasing RVV coverage, especially for pentavalent RVV. Further safety data are needed to support co-administration as a key tool to increase coverage.

BACKGROUND: Meningococcal serogroups A, B, C, W, and Y cause nearly all meningococcal disease, and comprehensive protection requires vaccination against all five serogroups. We aimed to assess the immunogenicity and safety of a pentavalent MenABCWY vaccine comprising two licensed vaccines-meningococcal serogroup B-factor H binding protein vaccine (MenB-FHbp) and a quadrivalent meningococcal serogroup ACWY tetanus toxoid conjugate vaccine (MenACWY-TT)-compared with two doses of MenB-FHbp and a single dose of quadrivalent meningococcal serogroup ACWY CRM197-conjugate vaccine (MenACWY-CRM) as the active control. We previously reported the primary safety and immunogenicity data relating to the two-dose MenB-FHbp schedule. Here we report secondary outcomes and ad-hoc analyses relating to MenABCWY immunogenicity and safety.
METHODS: We did an observer-blind, active-controlled trial at 68 sites in the USA, Czech Republic, Finland, and Poland. Healthy individuals (aged 10-25 years) who had or had not previously received a MenACWY vaccine were randomly assigned (1:2) using an interactive voice or web-based response system, stratified by previous receipt of a MenACWY vaccine, to receive 0·5 mL of MenABCWY (months 0 and 6) and placebo (month 0) or MenB-FHbp (months 0 and 6) and MenACWY-CRM (month 0) via intramuscular injection into the upper deltoid. All individuals were masked to group allocation, except staff involved in vaccine dispensation, preparation, and administration; and protocol adherence. Endpoints for serogroups A, C, W, and Y included the proportion of participants who achieved at least a four-fold increase in serum bactericidal antibody using human complement (hSBA) titres between baseline and 1 month after each vaccination. For serogroup B, secondary endpoints included the proportion of participants who achieved at least a four-fold increase in hSBA titres from baseline for each of four primary test strains and the proportion of participants who achieved titres of at least the lower limit of quantitation against all four test strains combined at 1 month after the second dose. Endpoints for serogroups A, C, W, and Y were assessed in the modified intent-to-treat (mITT) population, which included all randomly assigned participants who received at least one vaccine dose and had at least one valid and determinate MenB or serogroup A, C, W, or Y assay result before vaccination up to 1 month after the second dose, assessed in ACWY-experienced and ACWY-naive participants separately. Secondary endpoints for serogroup B were analysed in the evaluable immunogenicity population, which included all participants in the mITT population who were randomly assigned to the group of interest, received all investigational products as randomly assigned, had blood drawn for assay testing within the required time frames, had at least one valid and determinate MenB assay result after the second vaccination, and had no important protocol deviations; outcomes were assessed in both ACWY-experienced and ACWY-naive populations combined. Non-inferiority of MenABCWY to MenACWY-CRM and MenB-FHbp was determined using a -10% non-inferiority margin for these endpoints. Reactogenicity and adverse events were assessed among all participants who received at least one vaccine dose and who had available safety data. This trial is registered with Clinicaltrials.gov, NCT03135834, and is complete.
RESULTS: Between April 24 and November 10, 2017, 1610 participants (809 MenACWY-naive; 801 MenACWY-experienced) were randomly assigned: 544 to receive MenABCWY and placebo (n=272 MenACWY-naive; n=272 MenACWY-experienced) and 1066 to receive MenB-FHbp and MenACWY-CRM (n=537 MenACWY-naive; n=529 MenACWY-experienced). Among MenACWY-naive or MenACWY-experienced MenABCWY recipients, 75·5% (95% CI 69·8-80·6; 194 of 257; serogroup C) to 96·9% (94·1-98·7; 254 of 262; serogroup A) and 93·0% (88·4-96·2; 174 of 187; serogroup Y) to 97·4% (94·4-99·0; 224 of 230; serogroup W) achieved at least four-fold increases in hSBA titres against serogroups ACWY after dose 1 or 2, respectively, in ad-hoc analyses. Additionally, 75·8% (71·5-79·8; 320 of 422) to 94·7% (92·1-96·7; 396 of 418) of MenABCWY and 67·4% (64·1-70·6; 563 of 835) to 95·0% (93·3-96·4; 782 of 823) of MenB-FHbp recipients achieved at least four-fold increases in hSBA titres against MenB strains after dose 2 in secondary analyses; 79·9% (334 of 418; 75·7-83·6) and 74·3% (71·2-77·3; 605 of 814), respectively, achieved composite responses. MenABCWY was non-inferior to MenACWY-CRM (single dose) and to MenB-FHbp in ad-hoc analyses based on the proportion of participants with at least a four-fold increase in hSBA titres from baseline and (for MenB-FHbp only) composite responses. Reactogenicity events after vaccination were similarly frequent across groups, were mostly mild or moderate, and were unaffected by MenACWY experience. No adverse events causing withdrawals were related to the investigational product. Serious adverse events were reported in four (1·5%; 0·4-3·7) MenACWY-naive individuals in the MenABCWY group versus six (2·2%; 0·8-4·8) among MenACWY-experienced individuals in the MenABCWY group and 14 (1·3%; 0·7-2·2) in the active control group (MenACWY-experienced and MenACWY-naive individuals combined); none of these were considered related to the investigational product.
CONCLUSIONS: MenABCWY immune responses were robust and non-inferior to MenACWY-CRM and MenB-FHbp administered separately, and MenABCWY was well tolerated. The favourable benefit-risk profile supports further MenABCWY evaluation as a simplified schedule compared with current adolescent meningococcal vaccination programmes.
BACKGROUND: Pfizer.

Malaria transmission-blocking vaccines target mosquito-stage parasites and will support elimination programmes. Gamete vaccine Pfs230D1-EPA/Alhydrogel induced superior activity to zygote vaccine Pfs25-EPA/Alhydrogel in malaria-naive US adults. Here, we compared these vaccines in malaria-experienced Malians.
We did a pilot safety study then double-blind, block-randomised, comparator-controlled main-phase trial in malaria-intense Bancoumana, Mali. 18-50-year-old healthy non-pregnant, non-breastfeeding consenting adult residents were randomly assigned (1:1:1:1) to receive four doses at months 0, 1, 4·5, and 16·5 of either 47 μg Pfs25, 40 μg Pfs230D1 or comparator (Twinrix or Menactra)-all co-administered with normal saline for blinding-or 47 μg Pfs25 plus 40 μg Pfs230D1 co-administered. We documented safety and tolerability (primary endpoint in the as-treated populations) and immunogenicity (secondary endpoint in the as-treated populations: ELISA, standard-membrane-feeding assay, and mosquito direct skin feed assay). This trial is registered at ClinicalTrials.gov, NCT02334462.
Between March 19, and June 2, 2015, we screened 471 individuals. Of 225 enrolled for the pilot and main cohorts, we randomly assigned 25 participants to pilot safety cohort groups of five (20%) to receive a two-dose series of Pfs25-EPA/Alhydrogel (16 μg), Pfs230D1-EPA/Alhydrogel (15 μg) or comparator, followed by Pfs25-EPA/Alhydrogel (16 μg) plus Pfs230D1-EPA/Alhydrogel (15 μg) or comparator plus saline. For the main cohort, we enrolled 200 participants between May 11 and June 2, 2015, to receive a four-dose series of 47 μg Pfs25-EPA/Alhydrogel plus saline (n=50 [25%]; Pfs25), 40 μg Pfs230D1-EPA/Alhydrogel plus saline (n=49 [25%]; Pfs230D1), 47 μg Pfs25-EPA/Alhydrogel plus 40 μg Pfs230D1-EPA/Alhydrogel (n=50 [25%]; Pfs25 plus Pfs230D1), or comparator (Twinrix or Menactra) plus saline (n=51 [25%]). Vaccinations were well tolerated in the pilot safety and main phases. Most vaccinees became seropositive after two Pfs230D1 or three Pfs25 doses; peak titres increased with each dose thereafter (Pfs230D1 geometric mean: 77·8 [95% CI 56·9-106·3], 146·4 [108·3-198·0], and 410·2 [301·6-558·0]; Pfs25 geometric mean 177·7 [130·3-242·4] and 315·7 [209·9-474·6]). Functional activity (mean peak transmission-reducing activity) appeared for Pfs230D1 (74·5% [66·6-82·5]) and Pfs25 plus Pfs230D1 (68·6% [57·3-79·8]), after the third dose and after the fourth dose (88·9% [81·7-96·2] for Pfs230D1 and 85·0% [78·4-91·5] Pfs25 plus Pfs230D1) but not for Pfs25 (58·2% [49·1-67·3] after the third dose and 58·2% [48·5-67·9] after the fourth dose). Pfs230D1 transmission-reducing activity (73·7% [64·1-83·3]) persisted 10 weeks after the fourth dose. Transmission-reducing activity of 80% was estimated at 1659 ELISA units for Pfs25, 218 for Pfs230D1, and 223 for Pfs230D1 plus Pfs25. After 3850 direct skin feed assays, 35 participants (12 Pfs25, eight Pfs230D1, five Pfs25 plus Pfs230D1, and ten comparator) had transmitted parasites at least once. The proportion of positive assays in vaccine groups (Pfs25 33 [3%] of 982 [-0·013 to 0·014], Pfs230D1 22 [2%] of 954 [-0·005 to 0·027], and combination 11 [1%] of 940 [-0·024 to 0·002]) did not differ from that of the comparator (22 [2%] of 974), nor did Pfs230D1 and combination groups differ (-0·024 to 0·001).
Pfs230D1 but not Pfs25 vaccine induces durable serum functional activity in Malian adults. Direct skin feed assays detect parasite transmission to mosquitoes but increased event rates are needed to assess vaccine effectiveness.
Intramural Research Program of the National Institute of Allergy and Infectious Diseases and US National Institutes of Health.

BACKGROUND: Immunization with meningococcal ACWY conjugate vaccine induces protective antibodies against invasive meningococcal disease (IMD) caused by serogroups A, C, W and Y. We studied MenACWY-TT vaccine immunogenicity in adolescents with a heterogenous group of primary and secondary immune deficiency including patients with systemic lupus erythematosus, mixed connective tissue disease, vasculitis, uveitis, 22Q11 syndrome, sickle cell disease, and patients who underwent stem cell transplantation for bone marrow failure.
RESULTS: We enrolled 69 individuals aged 14-18 years diagnosed with a primary or secondary immune deficiency in a prospective observational cohort study. All patients received a single dose of MenACWY-TT vaccine during the catch-up campaign 2018-19 because of the IMD-W outbreak in the Netherlands. Capsular polysaccharide-specific (PS) IgG concentrations against MenACWY were measured before and 3-6, 12, and 24 months after vaccination. Overall, geometric mean concentrations (GMCs) of MenACWY-PS-specific IgG were lower in patients compared to data from healthy, aged-matched controls (n = 75) reaching significance at 12 months postvaccination for serogroup A and W (adjusted GMC ratios 0.26 [95% CI: 0.15-0.47] and 0.22 [95% CI: 0.10-0.49], respectively). No serious adverse events were reported by study participants.
CONCLUSIONS: The MenACWY conjugate vaccine was less immunogenic in adolescent patients with primary or secondary immunodeficiency compared to healthy controls, urging the need for further surveillance of these patients and supporting considerations for booster MenACWY conjugate vaccinations in these patient groups.

Men who have sex with men (MSM) have suboptimal uptake of human papillomavirus (HPV) and meningococcal vaccines. This study examines barriers and facilitators to HPV and meningococcal vaccination among MSM in a large, racially/ethnically diverse, and medically underserved U.S. region.
In 2020, we conducted five focus groups with MSM living in the Inland Empire, California. Participants discussed (1) their knowledge about and attitudes toward HPV, meningococcal disease, and related vaccines; and (2) factors that would encourage or discourage vaccine uptake. Data were systematically analyzed to identify salient barriers and facilitators to vaccination.
Participants (N = 25) had a median age of 29. Most were Hispanic (68%), self-identified as gay (84%), and had college degrees (64%). Key barriers to vaccination included: (1) limited awareness and knowledge about HPV and meningococcal disease, (2) reliance on mainstream healthcare providers for vaccine information, (3) stigma and reluctance to disclose sexual orientation, (4) uncertainty about health insurance coverage and vaccine costs, and (5) distance and time required to access vaccines. Key facilitators to vaccination were: (1) vaccine confidence, (2) perceived severity of HPV and meningococcal disease, (3) bundling vaccination into routine healthcare, and (4) pharmacies as vaccination sites.
Findings highlight opportunities for HPV and meningococcal vaccine promotion, including targeted education and awareness campaigns for MSM, LGBT inclusivity training for healthcare providers, and structural interventions to improve vaccine accessibility.

Immunogenicity to meningococcal serogroup ACWY (MenACWY) conjugate vaccine has not been studied in immunocompromised minors with juvenile idiopathic arthritis (JIA) or inflammatory bowel disease (IBD). We determined immunogenicity of a MenACWY-TT vaccine in JIA and IBD patients at adolescent age and compared results to data from aged-matched healthy controls (HCs).
We performed a prospective observational cohort study in JIA and IBD patients (14-18 years old), who received a MenACWY vaccination during a nationwide catch-up campaign (2018-2019) in the Netherlands. Primary aim was to compare MenACWY polysaccharide-specific serum IgG geometric mean concentrations (GMCs) in patients with HCs and secondary between patients with or without anti-TNF therapy. GMCs were determined before and 3-6, 12, and 24 months postvaccination and compared with data from HCs at baseline and 12 months postvaccination. Serum bactericidal antibody (SBA) titers were determined in a subset of patients at 12 months postvaccination.
We included 226 JIA and IBD patients (66 % and 34 % respectively). GMCs were lower for MenA and MenW (GMC ratio 0·24 [0·17-0·34] and 0·16 [0·10-0·26] respectively, p < 0·01) in patients compared to HCs at 12 months postvaccination. Anti-TNF users had lower MenACWY GMCs postvaccination compared with those without anti-TNF (p < 0·01). The proportion protected (SBA ≥ 8) for MenW was reduced in anti-TNF users (76 % versus 92 % in non-anti-TNF and 100 % in HCs, p < 0.01).
The MenACWY conjugate vaccine was immunogenic in the vast majority of JIA and IBD patients at adolescent age, but seroprotection was lower in patients using anti-TNF agents. Therefore, an extra booster MenACWY vaccination should be considered.

BackgroundMeningococcus (Neisseria meningitidis) is the causative bacteria of invasive meningococcal disease (IMD), a major cause of meningitis and sepsis. In 2015-16, an outbreak caused by serogroup C meningococci (MenC), belonging to the hyperinvasive strain ST-11(cc-11), resulted in 62 IMD cases in the region of Tuscany, Italy.AimWe aimed to estimate the key outbreak parameters and assess the impact of interventions used in the outbreak response.MethodsWe developed a susceptible-carrier-susceptible individual-based model of MenC transmission, accounting for transmission in households, schools, discos/clubs and the general community, which was informed by detailed data on the 2015-16 outbreak (derived from epidemiological investigations) and on the implemented control measures.ResultsThe outbreak reproduction number (Re) was 1.35 (95% prediction interval: 1.13-1.47) and the IMD probability was 4.6 for every 1,000 new MenC carriage episodes (95% confidence interval: 1.8-12.2). The interventions, i.e. chemoprophylaxis and vaccination of close contacts of IMD cases as well as age-targeted vaccination, were effective in reducing Re and ending the outbreak. Case-based interventions (including ring vaccination) alone would have been insufficient to achieve outbreak control. The definition of age groups to prioritise vaccination had a critical impact on the effectiveness and efficiency of control measures.ConclusionsOur findings suggest that there are no effective alternatives to widespread reactive vaccination during outbreaks of highly transmissible MenC strains. Age-targeted campaigns can increase the effectiveness of vaccination campaigns. These results can be instrumental to define effective guidelines for the control of future meningococcal outbreaks caused by hypervirulent strains.