Search Results (31)

Background/Objectives: This study aimed to evaluate the immunogenicity and safety of a Meningococcal A and C Polysaccharide Conjugate Vaccine in 3–5-month-old infants. A single-center, randomized, blinded, positive-controlled phase III clinical trial was conducted in Binyang County, Guangxi Zhuang Autonomous Region, China. Infants aged 3–5 months were randomly assigned to the experimental or control group at a 1:1 ratio. Both groups received 3 primary doses with a 1-month interval between each dose, and a booster dose administered at 18 months of age. Seroconversion rate, seropositivity rate, and GMT of bactericidal antibodies against Neisseria meningitidis groups A and C were assessed, along with adverse reactions within the full course of primary immunization and 30 days after booster immunization. Results: After primary immunization, in the experimental group’s pre-vaccination antibody-negative infants, seroconversion rates for groups A and C exceeded 90%, with antibody fold increases over 90 times; its seroconversion rates and GMT were non-inferior to the control group. Before the 18-month booster, the experimental group’s group A and C antibody seropositivity rates dropped to approximately 70% and 30% (slightly higher than the control), respectively. After booster immunization, the antibody levels against groups A and C were significantly higher than those before the booster and the positive rates and GMT levels of the two groups were similar. Adverse reactions were mainly solicited systemic ones (fever most common), with no statistical difference between groups. Conclusions: The experimental vaccine shows great immunogenicity and safety in infants aged 3–5 months and is non-inferior to the control vaccine. In the booster immunization phase of the control group, sequential vaccination with vaccines from different manufacturers was adopted, and the immunogenicity was good. Full article

Background/Objectives: Meningococcal disease (MD) remains a significant public health concern worldwide. In Serbia, mandatory immunization against MD with the meningococcal polysaccharide vaccine (MenAC) for high-risk groups and international travelers was introduced in 2006. Since 2017, the polysaccharide vaccine has been replaced with the quadrivalent meningococcal conjugate vaccine (MenACWY). The aim of this study was to analyze long-term trends in incidence, age-specific patterns, seasonality, and lethality of invasive meningococcal disease (IMD) in the Autonomous Province of Vojvodina (AP Vojvodina), Serbia, over a 28-year period. Methods: A descriptive study analyzed all reported cases of IMD in AP Vojvodina, from 1997 to 2024. Data were obtained from the regional communicable disease surveillance system, based on mandatory hospital reporting and case classification according to national and WHO guidelines. Temporal, demographic, and clinical characteristics, along with disease outcomes, were analyzed. Results: From 1997 to 2024, 175 IMD cases were reported in AP Vojvodina. The annual incidence peaked in 1997 (1.24/100,000), with smaller surges in 2003 and 2005. Since 2006, coinciding with the introduction of immunization against MD, a sustained decline has been observed, with incidence rarely exceeding 0.30/100,000. A slight resurgence occurred in 2023–2024, with 13 cases reported. From 1997 to 2024, IMD in AP Vojvodina exhibited a clear seasonal pattern, with most cases occurring in winter and early spring, peaking in January (17%), March (12%), and February (11%), and the fewest cases occuring in the summer months. Throughout the study period, the highest IMD incidence rates were consistently observed among infants <1 year of age and children aged 1–4 years, with peaks of up to 22.9/100,000 and 16.0/100,000, respectively. Incidence was much lower in older age groups, especially adults. After a 2006 peak, rates declined across all ages, with a slight resurgence in 2023–2024 among children and adolescents. Children aged 1–4 years made up the largest share of IMD cases, peaking in January–March (45.1%). Half of the infant cases were recorded in October–November, while cases in older children, adolescents, and adults were fewer and showed varied monthly patterns, with small peaks in winter and early spring. During the 28-year study period, the highest IMD mortality rate was observed among infants <1 year of age (0.59 per 100,000 population), followed by children aged 1–4 years (0.32 per 100,000). Mortality rates declined progressively with increasing age, with the lowest rate recorded among individuals aged ≥40 years (0.01 per 100,000). Of the 175 IMD cases reported in AP Vojvodina (1997–2024), 21 were fatal (case fatality rate [CFR] = 12.0%). The CFR of IMD varied across age groups. The highest CFR was observed among individuals aged ≥40 years (21.4%), followed by the 5–9 years (17.4%) and <1 year (16.7%) age groups. None of the patients had been vaccinated against MD. Fatal outcomes were more common in children aged 1–4 years and among rural residents, though differences were not statistically significant (p > 0.05). Most deaths (57.1%) occurred in the first quarter of the year. A strong association was found between clinical form and outcome, with meningococcal sepsis being significantly more frequently associated with fatality than meningitis (p = 0.0002). Deaths were sporadic over time, with most occurring within 1–2 days of notification. All confirmed fatal cases were due to serogroup B. Conclusions: MD remains a rare yet serious public health threat in AP Vojvodina. Mortality rates indicate that the public health impact of this disease is greatest among the youngest age groups; however, the risk of death, i.e., disease severity, does not appear to be age dependent. The recent rise in cases, high fatality among sepsis patients, and absence of prior vaccination among all IMD cases highlight the need for enhanced surveillance, physician education, and consideration of introducing both MenACWY and MenB vaccines for high-risk groups. Full article

Background: The combined diphtheria–tetanus–acellular pertussis (three-component), Haemophilus influenzae type b (Hib, conjugate), and ACYW135 meningococcal (conjugate) vaccine (DTaP-Hib-MCV4) offers a promising alternative to single-component vaccines, potentially simplifying immunization schedules and improving vaccination coverage. Methods: We evaluated the safety, immunogenicity, and protective efficacy of DTaP-Hib-MCV4 in animal models. Acute and long-term toxicity studies were conducted in Sprague-Dawley (SD) rats with equal numbers of male and female animals. Immunogenicity was assessed in female NIH mice and SD rats using a three-dose regimen at 14-day intervals. Orbital blood was collected 14 days post-immunization to measure IgG titers against pertussis, diphtheria, tetanus, Hib, and meningococcal antigens. The protective efficacy was determined using potency tests for the pertussis, diphtheria, and tetanus components; passive protection studies for Hib; and serum bactericidal antibody (SBA) titers against A/C/Y/W135 meningococcal serogroups. Results: Acute and repeated-dose toxicity studies in SD rats showed no signs of abnormal toxicity or irritation at either high (three doses/rat) or low (one dose/rat) doses levels. The no-observed-adverse-effect level (NOAEL) for DTaP-Hib-MCV4 was established at three doses/rat after 8 weeks of repeated intramuscular administration and a 4-week recovery period. Specific IgG antibodies against all the vaccine components were detected in animal sera at both one and three doses/rat, with no evidence of immunotoxicity. Following two-dose primary immunization in murine models, the combined vaccine elicited robust antigen-specific antibody responses, with geometric mean titers (GMTs) as follows: 1,280,000 for pertussis toxin (PT); 761,093 for filamentous hemagglutinin (FHA); 1,159,326 for pertactin (PRN); 1,659,955 for diphtheria toxoid (DT); 1,522,185 for tetanus toxoid (TT); 99 for Haemophilus influenzae type b (Hib); and 25,600, 33,199, 8300, and 9051 for serogroups A, C, Y, and W135 of Neisseria meningitidis, respectively. In the rat models, three-dose primary immunization also elicited robust antigen-specific antibody responses. Protection studies demonstrated efficacy against pertussis, tetanus toxin, and diphtheria toxin challenges. In the Hib challenge study, none of the 10 animals given anti-DTaP-Hib-MCV4 antiserum developed bacteremia after the live Hib challenge (vs. 5814/0.1 mL in the negative control, p < 0.001). In addition, the SBA titers against meningococcal serogroups exceeded the protective threshold (≥1:8) in 92.2% of the immunized mice and 100% of the immunized rats. Crucially, the combined vaccine induced potent immune responses and protective efficacy, with antibody levels and protection against each component antigen comparable to or greater than those of the individual components: DTaP, Hib, and MCV4. Conclusions: These findings demonstrate that the DTaP-Hib-MCV4 combined vaccine is both safe and immunogenic, supporting its potential as a viable alternative to individual vaccines. This combined vaccine may streamline immunization programs and enhance vaccination coverage. Full article

Background: The Spanish Interterritorial Council of the National Health System (a central government body) currently recommends vaccination against meningococcal serogroup C (MenC) at 4 and 12 months of age for prevention of invasive meningococcal disease (IMD). The Advisory Committee on Vaccines of the Spanish Association of Pediatrics (a professional medical association) and numerous Spanish regional bodies instead recommend quadrivalent vaccination against serogroups A, C, W, and Y (MenACWY) at 4 and 12 months of age. The central government and Spanish Association of Pediatrics also recommend MenACWY vaccination at 12 years of age. This study assessed the potential public health effects of replacing the MenC vaccination schedule with different MenACWY vaccination schedules in infants. Methods: Here, a static multi-cohort population model was used to evaluate potential effects on public health of IMD due to meningococcal serogroups C/W/Y, comparing MenC infant vaccination (reference strategy) against four different strategies including quadrivalent tetanus toxoid conjugate vaccine (MenACWY-TT; Nimenrix^®, Pfizer Europe MA EEIG, Brussels, Belgium) infant vaccination; all strategies included MenACWY-TT vaccination at 12 years of age. Results: The most effective strategy for infant vaccination was MenACWY-TT at 2, 4, and 12 months, preventing an estimated additional 103 IMD cases, 17 deaths, and 41 cases with long-term sequelae (LTS) versus the reference strategy in the base-case IMD incidence scenario. When strategies included a two-dose infant schedule, the earlier the infant MenACWY-TT vaccine was administered, the more additional cases, deaths, and cases with LTS were prevented (base-case and high-incidence scenarios). Conclusions: This analysis supports implementation of MenACWY-TT as a replacement for MenC vaccination. Full article

Objectives: The purpose of this study was to further characterize the ultrafiltration (UF) method for determining free saccharide levels in glycoconjugate vaccines and compare it with other methods used for the determination of free saccharide levels in meningococcal glycoconjugate vaccines. Methods: We performed experiments on both meningococcal glycoconjugates and capsular polysaccharides, and compared UF, deoxycholate (DOC) precipitation, and solid-phase extraction (SPE) methods. Meningococcal capsular polysaccharides from groups A (MenA), C (MenC), and W (MenW) were depolymerized and characterized using SEC-MALS (size-exclusion chromatography with multi-angle laser light scattering) to determine the molecular weight and hydrodynamic size and then subjected to UF. The free saccharide content was quantified using HPAEC-PAD (high-performance anion-exchange chromatography with pulsed amperometric detection). Results: The characterization of size-reduced group C polysaccharide revealed weight-average molecular mass (Mw) ranging from 22,200 g/mol to 287,300 g/mol and hydrodynamic radii of 3.7 to 19.5 nm. Pore size studies confirmed that polysaccharides with diameters up to 15 nm filtered through the 100 kDa cellulose membrane. The smallest PS fragment tested (22,200 g/mol, 7.4 nm diameter) was partially recovered from the 30 kDa membrane. For MenC-CRM₁₉₇, DOC yielded the lowest free saccharide content (<1%), UF gave moderate results (7–8%), and SPE showed the highest and most variable values (up to 15%). For MenA- and MenW-CRM₁₉₇, UF and DOC consistently provided low free saccharide levels (<2% and 3–11%, respectively). Conclusions: The upper limits on the size of free group C meningococcal polysaccharides that can be ultrafiltered were assessed. Differences in the relative amount of free saccharide were observed between various methods used to control meningococcal conjugate vaccines. Full article

Multivalent meningococcal conjugate vaccines are a significant focus for the scientific community in light of the WHO’s mission to defeat meningitidis by 2030. Well-known meningococcal vaccines such as MenAfriVac, Nimenrix, Menveo, and MenQuadfi are licensed in various parts of the world and have been successful. Recently, the World Health Organization (WHO) qualified MenFive (meningococcal A, C, Y, W, and X) conjugate vaccine, further enhancing the battery of vaccines against meningitis. The antigenic nature of the current and new serogroups, the selection of carrier proteins, and the optimal formulation of these biomolecules are pivotal parameters for determining whether a biological preparation qualifies as a vaccine candidate. Creating appropriate quality control analytical tools for a complex biological formulation is challenging. A scoping review aims to identify the main challenges and gaps in analyzing multivalent vaccines, especially in the case of novel serogroups, such as X, as the limited literature addresses these analytical challenges. In summary, the similarities in polysaccharide backbones between meningococcal serogroups (C, Y, W sharing a sialic acid backbone and A, X sharing a phosphorous backbone) along with various conjugation chemistries (such as CNBr activation, reductive amination, CDAP, CPIP, thioether bond formation, N-hydroxy succinimide activation, and carbodiimide-mediated coupling) resulting into a wide variety of polysaccharide -protein conjugates. The challenge in analyzing carrier proteins used in conjugation (such as diphtheria toxoid, tetanus toxoid, CRM diphtheria protein, and recombinant CRM) is assessing their purity (whether they are monomeric or polymeric in nature as well as their polydispersity). Additional analytical challenges include the impact of excipients, potential interference from serogroups, selection and establishment of standards, age-dependent behavior of biomolecules indicated by molecular size distributions, and process-driven variations. This article explains the analytical insights gained (polysaccharide content, free saccharide, free proteins, MSD) during the development of the MenFive vaccine and highlights the crucial gaps and challenges in testing. Full article

Background: The Banalia health zone in the Democratic Republic of Congo reported a meningitis epidemic in 2021 that evolved outside the epidemic season. We assessed the effects of the meningitis epidemic response. Methods: The standard case definition was used to identify cases. Care was provided to 2651 in-patients, with 8% of them laboratory tested, and reactive vaccination was conducted. To assess the effects of reactive vaccination and treatment with ceftriaxone, a statistical analysis was performed. Results: Overall, 2662 suspected cases of meningitis with 205 deaths were reported. The highest number of cases occurred in the 30–39 years age group (927; 38.5%). Ceftriaxone contributed to preventing deaths with a case fatality rate that decreased from 70.4% before to 7.7% after ceftriaxone was introduced (p = 0.001). Neisseria meningitidis W was isolated, accounting for 47/57 (82%), of which 92% of the strains belonged to the clonal complex 11. Reactive vaccination of individuals in Banalia aged 1–19 years with a meningococcal multivalent conjugate (ACWY) vaccine (Menactra^®) coverage of 104.6% resulted in an 82% decline in suspected meningitis cases (incidence rate ratio, 0.18; 95% confidence interval, 0.02–0.80; p = 0.041). Conclusion: Despite late detection (two months) and reactive vaccination four months after crossing the epidemic threshold, interventions implemented in Banalia contributed to the control of the epidemic. Full article

Background: Children and adolescents living with HIV (CALHIV) are at high risk of meningococcal infections and may present lower immune responses to vaccines. The objectives of this study were to assess the immunogenicity of the quadrivalent Men ACWY-TT vaccine (Nimenrix^®) in CALHIV after a two-dose schedule and to describe possible HIV-related factors that may affect the immunogenic response. Methods: A multicenter prospective study was designed, including CALHIV followed in five hospitals in Madrid, between 2019 and 2021. Two doses of the Men ACWY-TT vaccine were administered. Serum bactericidal antibody (SBA) assays using rabbit complement (rSBA) against serogroups C, W, and Y were used to determine seroprotection and vaccine response (the proportion achieving a putative protective titer of ≥eight or a ≥four-fold rise in titer from baseline). Serum was collected at baseline, and at 3 and 12 months after vaccination. Results: There were 29 CALHIV included, 76% of whom were perinatally infected. All were receiving TAR and presented a good immunovirological and clinical status overall. At baseline, 45% of CALHIV had seroprotective titers to at least one serogroup, with individual seroprotection rates of 24%, 28%, and 32% against C, W, and Y, respectively. After a two-dose schedule, vaccine response was 83% for each serogroup, eliciting a vaccine response to all serogroups in 69% of them. One year after vaccination, 75% of CALHIV maintained seroprotective titers against the C serogroup, and 96% against W and Y. None of the HIV-related characteristics analyzed could predict vaccine response or antibody duration. Conclusions: CALHIV who received effective TAR and presented a good immuno-virological situation achieved an appropriate vaccine response after two doses of the Men ACWY-TT vaccine, and antibody-mediated protection against serogroups C, W, and Y was maintained in more than 70% of the patients one year after vaccination. Full article

Surveillance of meningococcal disease (MD) is crucial after the implementation of vaccination strategies to monitor their impact on disease burden. Adolescent vaccination could provide direct and indirect protection. Argentina, Brazil, and Chile have introduced meningococcal conjugate vaccines (MCV) into their National Immunization Programs (NIP), while Uruguay has not. Here, we analyze the epidemiology of MD and vaccination experience from these four South American countries to identify needs and plans to improve the current vaccination programs. Methodology: Descriptive study of MD incidence rates, serogroup distribution, case fatality rates (CFR), and MCV uptakes during the period 2010–2021 in Argentina, Brazil, Chile, and Uruguay. Data were extracted from national surveillance programs, reference laboratories, NIPs, and Pubmed. Results: MD overall incidence from 2010 to 2021 have a decreasing trend in Argentina (0.37 [IQR = 0.20–0.61]), Brazil (0.59 [IQR = 0.54–1.22]), and Chile (0.45 [IQR = 0.40–0.77]), while a significant increase in Uruguay (0.47 [IQR = 0.33–0.69]) was found from 2016 to 2019. During the COVID-19 pandemic, all countries sharply reduced their MD incidence. The highest incidence rates were observed among infants, followed by children 1–4 years of age. No second peak was evident in adolescents. A reduction in serogroup C, W, and Y cases has occurred in Argentina, Brazil, and Chile after introduction of MCV, serogroup B becoming predominant in all four countries. Median CFR was 9.0%, 21%, 19.9%, and 17.9% in Argentina, Brazil, Chile, and Uruguay, respectively. Median uptake of MCV for Argentina and Brazil were 66.6% and 91.0% for priming in infants; 54.7% and 84.5% for booster in toddlers; and 47.5% and 53% for adolescents; while for Chile, 95.6% for toddlers. Conclusions: Experience after the implementation of MCV programs in South America was successful, reducing the burden of MD due to the vaccine serogroups. High vaccine uptake and the inclusion of adolescents will be crucial in the post-pandemic period to maintain the protection of the population. The increase in the proportion of serogroup B cases emphasizes the importance of continuous surveillance to guide future vaccination strategies. Full article

Background: Understanding the drivers of coverage for vaccines offered in the second year of life (2YL) is a critical focus area for Ghana’s life course approach to vaccination. This study characterizes the predictors of vaccine receipt for 2YL vaccines—meningococcal serogroup A conjugate vaccine (MACV) and the second dose of measles-containing vaccine (MCV2)—in Ghana. Methods: 1522 children aged 18–35 months were randomly sampled through household surveys in the Greater Accra Region (GAR), Northern Region (NR), and Volta Region (VR). The association between predictors and vaccination status was modeled using logistic regression with backwards elimination procedures. Predictors included child, caregiver, and household characteristics. Results: Coverage was high for infant vaccines (>85%) but lower for 2YL vaccines (ranging from 60.2% for MACV in GAR to 82.8% for MCV2 in VR). Predictors of vaccination status varied by region. Generally, older, first-born children, those living in rural settlements and those who received their recommended infant vaccines by their first birthday were the most likely to have received 2YL vaccines. Uptake was higher among those with older mothers and children whose caregivers were aware of the vaccination schedule. Conclusions: Improving infant immunization uptake through increased community awareness and targeted strategies, such as parental reminders about vaccination visits, may improve 2YL vaccination coverage. Full article

Discrimination and limited access to healthcare services in remote areas can affect vaccination coverage. Therefore, this study aimed to estimate vaccination coverage for children living in quilombola communities and rural settlements in the central region of Brazil during their first year of life and to analyze the factors associated with incomplete vaccination. An analytical cross-sectional study was conducted on children born between 2015 and 2017. The percentage of children who received all vaccines recommended by the National Immunization Program in Brazil by 11 months and 29 days was used to calculate immunization coverage. Children who received the following vaccines were considered as having a complete basic vaccination schedule: one dose of BCG; three doses of Hepatitis B, of Diphtheria-Tetanus-Pertussis (DPT), of Haemophilus influenzae type b (Hib), and of Poliovirus (Polio); two doses of Rotavirus, of 10-valent pneumococcal (PCV10), and of Serogroup C meningococcal conjugate (MenC); and one dose of Yellow Fever (YF). Measles-mumps-rubella (MMR) and other doses recommended at or after 12 months were not included. Consolidated logistic regression was used to identify factors associated with incomplete vaccination coverage. Overall vaccination coverage was 52.8% (95% CI: 45.5–59.9%) and ranged from 70.4% for the Yellow Fever vaccine to 78.3% for the Rotavirus vaccine, with no significant differences between the quilombola and settler groups. Notably, the likelihood of incomplete general vaccination coverage was higher among children who did not receive a visit from a healthcare professional. Urgent strategies are required to achieve and ensure health equity for this unique and traditionally distinct group with low vaccination coverage. Full article

Vaccines remain a fundamental intervention for preventing illness and death. In the United States, suboptimal vaccine uptake in adolescents and young adults has been observed for meningococcal conjugate (MenACWY) and serogroup B meningococcal (MenB) vaccines, particularly among marginalized communities, despite current recommendations by the Advisory Committee on Immunization Practices. A systematic literature search was conducted in the MEDLINE and MEDLINE In-Process, Embase, Cochrane, PsychInfo, and CINAHL databases to identify both drivers of, and barriers to, MenACWY and MenB vaccine uptake in adolescents and young adults. A total of 34 of 46 eligible studies that presented outcomes stratified by race/ethnicity, geography, and socioeconomic status were selected for review. Results showed MenACWY and MenB vaccination coverage in adolescents and young adults is impacted by racial/ethnic, socioeconomic, and geographic disparities. Gaps also exist in insurance for, or access to, these vaccines in adolescents and young adults. Moreover, there was variability in the understanding and implementation of the shared decision-making recommendations for the MenB vaccine. Disease awareness campaigns, increased clarity in accessing all meningococcal vaccines, and further research on the relationships between measures of marginalization and its impact on vaccine coverage in adolescents and young adults are needed to reduce the incidence of severe infections. Full article

Over the last decades, different quadrivalent antimeningococcal vaccine formulations (diphteria toxoid conjugate, MenACWY-D; tetanus toxoid conjugate, MenACWY-TT; CRM₁₉₇ protein conjugate, MenACWY-CRM) have been developed. However, their availability varies, both in terms of authorized formulations and of inclusion in vaccination schedules. Furthermore, several countries include only the monovalent meningococcal C (MenC) vaccine in their immunization programmes. Finally, there is currently no updated systematic review that directly compares the MenACWY formulations. Thus, we summarized the evidence on efficacy and safety through four parallel, independent systematic literature reviews with meta-analysis which included randomized controlled trials comparing the abovementioned vaccines. A total of 16 studies have been included. In terms of efficacy, MenACWY-TT outperformed MenACWY-D and MenACWY-CRM for A, W-135, and Y serogroups, while no significant difference was found for serogroup C. Furthermore, we did not find significant differences in efficacy between MenC and MenACWY-TT. Regarding the safety, we were able to perform a quantitative analysis only between MenACWY-TT and MenC, finding no significant differences. Similarly, among the different MenACWY formulations no relevant differences were identified. These findings suggest that MenACWY-TT could be preferable to other formulations to improve current vaccination programs and to better develop future immunization policies. Full article

Preterm and small-for-gestational-age (SGA) infants are more susceptible to vaccine-preventable diseases. To evaluate routine vaccination timeliness in these high-risk groups, a full birth cohort of infants (n = 41,502) born in 2017 and 2018 in Tuscany was retrospectively followed up until 24 months of age. Infants were classified by gestational age (GA) and SGA status. The vaccinations included: hexavalent (HEXA), measles-mumps-rubella, varicella, pneumococcal conjugate (PCV), and meningococcal C conjugate. Time-to-event (Kaplan–Meier) analyses were conducted to evaluate the timing of vaccination according to GA; logistic models were performed to evaluate the associations between GA and SGA with vaccination timeliness. Time-to-event analyses show that the rate of delayed vaccine receipt increased with decreasing GA for all the vaccinations, with a less marked gradient in later vaccine doses. Compared to full-term infants, very preterm infants significantly showed an increased odds ratio (OR) for delayed vaccination in all the vaccinations, while moderate/late preterm infants only showed an increased OR for HEXA-1, HEXA-3, PCV-1, and PCV-3. SGA infants had a significantly higher risk of delayed vaccination only for HEXA-1 and PCV-1 compared to non-SGA infants. In conclusion, vaccinations among preterm and SGA infants showed considerable delay. Tailored public health programs to improve vaccination timeliness are required in these high-risk groups. Full article

GMMA are outer membrane vesicles (OMVs) released from Gram-negative bacteria genetically modified to enhance OMVs formation that have been shown to be optimal systems to enhance immunogenicity of protein antigens. Here, we selected Neisseria meningitidis factor H binding protein (fHbp) and used the conjugation chemistry as a tool to alter antigen orientation on GMMA. Indeed, fHbp was randomly linked to GMMA or selectively attached via the N-terminus to mimic native presentation of the protein on the bacterial surface. Interestingly, protein and peptide array analyses confirmed that antibodies induced by the selective and the random conjugates showed a pattern very similar to fHbp natively expressed on bacterial surfaces or to the recombinant protein mixed with GMMA, respectively. However, the two conjugates elicited antibodies with similar serum bactericidal activity against meningococcal strains, superior to the protein alone or physically mixed with GMMA. Presentation of fHbp on GMMA strongly enhances the functional immune response elicited by the protein but its orientation on the bacterial surface does not have an impact. This study demonstrates the flexibility of the GMMA platform as a display and delivery system for enhancing antigen immunogenicity and further supports the use of such promising technology for the development of effective vaccines. Full article