RESUMEN
Two vaccines are available to prevent serogroup B meningococcal disease, i.e. the four-component meningococcal serogroup B vaccine (4CMenB) and the bivalent-factor-H-binding-protein meningococcal serogroup B vaccine (MenB-fHbp). Currently, 4CMenB is offered as part of routine infant immunization schedules. Available immunogenicity data showed a progressive decline in protective serum bactericidal antibodies (SBA) titers, with a re-enhancement following a booster dose during infancy. Responses did not seem to be long-lasting and vaccinated individuals might be at risk of meningococcal diseases during adolescence. Only one study evaluated the possibility to administer a single booster dose to immunocompetent adolescents who received a primary series during infancy. Despite a high proportion of enrollees achieving protective SBA levels 28 days post-booster, titers tended to decrease 1 year after. Immunocompetent adolescents who received a primary series and a booster during the first two years of life might rather benefit from re-vaccination against MenB; current evidence does not support the possibility of a booster.
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Anticuerpos Antibacterianos , Esquemas de Inmunización , Inmunización Secundaria , Infecciones Meningocócicas , Vacunas Meningococicas , Neisseria meningitidis Serogrupo B , Humanos , Vacunas Meningococicas/inmunología , Vacunas Meningococicas/administración & dosificación , Neisseria meningitidis Serogrupo B/inmunología , Adolescente , Infecciones Meningocócicas/prevención & control , Infecciones Meningocócicas/inmunología , Lactante , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Política de SaludRESUMEN
BACKGROUND: Percentage uptake of some meningococcal vaccines is low in the US. Understanding what drives vaccination preferences may help to increase vaccination rates. OBJECTIVES: To determine how attributes of meningococcal vaccines and the availability of a pentavalent (MenABCWY) vaccine profile drive adolescents' and young people's (AYP's) willingness to be vaccinated and parents' and legal guardians' (PLG') willingness for their child to be vaccinated (WTV). To also explore how preferences for meningococcal vaccines vary by participant characteristics. METHODS: Vaccine preferences were elicited in a discrete choice experiment (DCE) with AYP aged 16-23 years and PLG of adolescents aged 11-17 years. Participants chose between two hypothetical vaccine profiles that differed in level of protection, dosing, and risks of mild-to-moderate and severe side effects, and a no vaccination profile. Main outcome measures were relative attribute importance (RAI) and WTV. RAI measured the maximum contribution of an attribute to vaccination choice relative to other attributes. WTV compared predicted choice probabilities for the three vaccine profiles. RESULTS: 407 AYP and 394 PLG participated (50.9% male, 78.4% White/Caucasian). Irrespective of vaccine attributes, 59.5% always opted into vaccination and 3.6% always opted out of vaccination. The most important attributes were level of protection (RAI: 33.7%) and risk of mild-to-moderate side effects (RAI: 32.3%). Dosing was more important to PLG (RAI: 5.9%) than AYP (RAI: 2.0%; p < .01). Adding a pentavalent vaccine alternative increased WTV by 3.7 percentage points (PP) for PLG, 2.4 PP for AYP, 16.4 PP for vaccine-hesitant participants, 13.4 PP for participants without health insurance, and 9.6 PP for adults. CONCLUSION: Level of protection and risk of mild-to-moderate side effects were the most important vaccine attributes. Adding a pentavalent vaccine alternative increased WTV particularly among adults, individuals who were vaccine-hesitant, and individuals without health insurance.
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Infecciones Meningocócicas , Vacunas Meningococicas , Padres , Vacunación , Humanos , Adolescente , Vacunas Meningococicas/inmunología , Vacunas Meningococicas/administración & dosificación , Vacunas Meningococicas/efectos adversos , Masculino , Femenino , Infecciones Meningocócicas/prevención & control , Infecciones Meningocócicas/inmunología , Padres/psicología , Vacunación/psicología , Vacunación/métodos , Adulto Joven , Niño , Estados Unidos , Adulto , Prioridad del PacienteRESUMEN
OBJECTIVES: To estimate vaccine effectiveness (VE) and duration of protection of single primary and booster immunisation with meningococcal C (MenC) and ACWY (MenACWY) conjugate vaccines in preventing MenC invasive meningococcal disease (IMD). METHODS: We performed a systematic review on studies of VE and immunogenicity (rSBA/hSBA titers) of participants aged 12-23 months for primary and 6-18 years for booster immunisation (last search: 18 August 2023). Risk of bias and certainty of evidence were evaluated (PROSPERO: CRD42020178773). RESULTS: We identified 10 studies. Two studies reported VE of primary immunisation with MenC vaccines ranging between 90% (74.9 - 96.1) and 84.1% (41.5 - 95.7) for periods of 2 and 7 years, respectively. Eight studies reported immunogenicity of primary immunisation with MenC and/or MenACWY vaccines, of which two reported -in addition- on booster immunisation. The percentage of participants with protective rSBA titers was high after primary immunisation but waned over the following 6 years. A single booster at the age of 7 years or older seems to prolong protection for several years. CONCLUSIONS: A single dose of MenC or MenACWY vaccine at 12-23 months of age provides robust protection against MenC IMD. Data on booster immunisation are sparse, but indicate prolonged protection for three years at least.
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Inmunización Secundaria , Infecciones Meningocócicas , Vacunas Meningococicas , Humanos , Vacunas Meningococicas/inmunología , Vacunas Meningococicas/administración & dosificación , Infecciones Meningocócicas/prevención & control , Infecciones Meningocócicas/inmunología , Adolescente , Niño , Neisseria meningitidis Serogrupo C/inmunología , Eficacia de las Vacunas , Lactante , Vacunas Conjugadas/inmunología , Vacunas Conjugadas/administración & dosificación , Esquemas de Inmunización , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Masculino , FemeninoRESUMEN
The 4-component meningococcal serogroup B (MenB) vaccine, 4CMenB, the first broadly protective, protein-based MenB vaccine to be licensed, is now registered in more than 50 countries worldwide. Real-world evidence (RWE) from the last decade confirms its effectiveness and impact, with infant immunization programs showing vaccine effectiveness of 71-95% against invasive MenB disease and cross-protection against non-B serogroups, including a 69% decrease in serogroup W cases in 4CMenB-eligible cohorts in England. RWE from different countries also demonstrates the potential for additional moderate protection against gonorrhea in adolescents. The real-world safety profile of 4CMenB is consistent with prelicensure reports. Use of the endogenous complement human serum bactericidal antibody (enc-hSBA) assay against 110 MenB strains may enable assessment of the immunological effectiveness of multicomponent MenB vaccines in clinical trial settings. Equitable access to 4CMenB vaccination is required to better protect all age groups, including older adults, and vulnerable groups through comprehensive immunization policies.
Invasive meningococcal disease, caused by the bacterium Neisseria meningitidis(meningococcus), is rare but often devastating and can be deadly. Effective vaccines are available, including vaccines against meningococcal serogroup B disease. In 2013, the 4-component meningococcal serogroup B vaccine, 4CMenB, became the first broadly protective, protein-based vaccine against serogroup B to be licensed, with the second (bivalent vaccine, MenB-FHbp) licensed the following year. 4CMenB is now registered in more than 50 countries, in the majority, for infants and all age groups. In the US, it is approved for individuals aged 1025 years. Evidence from immunization programs in the last decade, comparing vaccinated and unvaccinated individuals and the same population before and after vaccination, confirms the effectiveness and positive impact of 4CMenB against serogroup B disease. This also demonstrates that 4CMenB can provide protection against invasive diseases caused by other meningococcal serogroups. Furthermore, N. meningitidis is closely related to the bacterium that causes gonorrhea, N. gonorrhoeae, and emerging real-world evidence suggests that 4CMenB provides additional moderate protection against gonococcal disease. The safety of 4CMenB when given to large numbers of infants, children, adolescents, and adults is consistent with the 4CMenB safety profile reported before licensure.For the future, it would be beneficial to address differences among national guidelines for the recommended administration of 4CMenB, particularly where there is supportive epidemiological evidence but no equitable access to vaccination. New assays for assessing the potential effectiveness of meningococcal serogroup B vaccines in clinical trials are also required because serogroup B strains circulating in the population are extremely diverse across different countries.
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Infecciones Meningocócicas , Vacunas Meningococicas , Humanos , Vacunas Meningococicas/inmunología , Vacunas Meningococicas/administración & dosificación , Infecciones Meningocócicas/prevención & control , Infecciones Meningocócicas/inmunología , Infecciones Meningocócicas/epidemiología , Neisseria meningitidis Serogrupo B/inmunología , Programas de Inmunización , Gonorrea/prevención & control , Gonorrea/inmunología , Vacunación , Lactante , Adolescente , Protección Cruzada/inmunologíaRESUMEN
Neisserial adhesin A (NadA) is a meningococcal surface protein included as recombinant antigen in 4CMenB, a protein-based vaccine able to induce protective immune responses against Neisseria meningitidis serogroup B (MenB). Although NadA is involved in the adhesion/invasion of epithelial cells and human myeloid cells, its function in meningococcal physiology is still poorly understood. To clarify the role played by NadA in the host-pathogen interaction, we sought to identify its cellular receptors. We screened a protein microarray encompassing 2,846 human and 297 mouse surface/secreted recombinant proteins using recombinant NadA as probe. Efficient NadA binding was revealed on the paired sialic acid-binding immunoglobulin-type lectins receptors 5 and 14 (Siglec-5 and Siglec-14), but not on Siglec-9 therein used as control. The interaction was confirmed by biochemical tools with the determination of the KD value in the order of nanomolar and the identification of the NadA binding site by hydrogen-deuterium exchange coupled to mass spectrometry. The N-terminal domain of the Siglec-5 that recognizes the sialic acid was identified as the NadA binding domain. Intriguingly, exogenously added recombinant soluble Siglecs, including Siglec-9, were found to decorate N. meningitidis surface in a NadA-dependent manner. However, Siglec-5 and Siglec-14 transiently expressed in CHO-K1 cells endorsed NadA binding and increased N. meningitidis adhesion/invasion while Siglec-9 did not. Taken together, Siglec-5 and Siglec-14 satisfy all features of NadA receptors suggesting a possible role of NadA in the acute meningococcal infection.IMPORTANCEBacteria have developed several strategies for cell colonization and immune evasion. Knowledge of the host and pathogen factors involved in these mechanisms is crucial to build efficacious countermoves. Neisserial adhesin A (NadA) is a meningococcal surface protein included in the anti-meningococcus B vaccine 4CMenB, which mediates adhesion to and invasion of epithelial cells. Although NadA has been shown to bind to other cell types, like myeloid and endothelial cells, it still remains orphan of a defined host receptor. We have identified two strong NadA interactors, Siglec-5 and Siglec-14, which are mainly expressed on myeloid cells. This showcases that NadA is an additional and key player among the Neisseria meningitidis factors targeting immune cells. We thus provide novel insights on the strategies exploited by N. meningitidis during the infection process, which can progress to a severe illness and death.
Asunto(s)
Adhesinas Bacterianas , Antígenos CD , Antígenos de Diferenciación Mielomonocítica , Adhesión Bacteriana , Interacciones Huésped-Patógeno , Lectinas , Humanos , Adhesinas Bacterianas/metabolismo , Adhesinas Bacterianas/genética , Antígenos CD/metabolismo , Antígenos CD/genética , Lectinas/metabolismo , Lectinas/genética , Lectinas/inmunología , Animales , Antígenos de Diferenciación Mielomonocítica/metabolismo , Antígenos de Diferenciación Mielomonocítica/genética , Unión Proteica , Ratones , Células CHO , Cricetulus , Neisseria meningitidis/genética , Neisseria meningitidis/metabolismo , Neisseria meningitidis/inmunología , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/genética , Lectinas Similares a la Inmunoglobulina de Unión a Ácido Siálico/metabolismo , Lectinas Similares a la Inmunoglobulina de Unión a Ácido Siálico/genética , Células Epiteliales/microbiología , Células Epiteliales/metabolismo , Células Epiteliales/inmunología , Infecciones Meningocócicas/microbiología , Infecciones Meningocócicas/inmunología , Receptores de Superficie Celular/metabolismo , Receptores de Superficie Celular/genética , Neisseria meningitidis Serogrupo B/genética , Neisseria meningitidis Serogrupo B/inmunología , Neisseria meningitidis Serogrupo B/metabolismoRESUMEN
Meningococcal disease is caused by Neisseria meningitidis or meningococcus. Every year globally around 1.2 million people are affected and approximately 120,000 deaths occur due to meningitis. The disease can be prevented by a single dose of meningococcal vaccine. We carried out a randomized observer-blinded non-inferiority trial to evaluate and compare the immunogenicity and safety of a local meningococcal polysaccharide vaccine 'Ingovax ACWY' (test) with Quadri MeningoTM (comparator), an approved meningococcal polysaccharide vaccine in India. A total of 88 healthy adults (18-45 years old) were randomized at a 1:1 ratio in two vaccine groups receiving a single dose vaccine subcutaneously. All participants were followed until three months post-vaccination. Blood for clinical parameters (hematology and biochemistry) and serum bactericidal assay (SBA) was collected prior to vaccination and one-month post-vaccination. Solicited adverse events (AEs) were assessed up to 6 days following vaccination and unsolicited AEs were monitored throughout the follow-up period. There was no significant difference in rates of AE between the two groups. The commonest solicited AE was injection site pain. No serious AEs were reported. There was no significant difference (p<0.05) in seroconversion rate as well as pre and post-vaccination SBA geometric mean titers (GMT)between test and comparator vaccine. The post-vaccination GMT ratio (GMR) of the test and comparator vaccine was found to be 0.9, 1, 1.29, and 0.85 for serogroup A, C, W135, and Y respectively. For all the serogroups, lower limit of 95% CI of the GMR was found to be greater than the pre-defined 0.5 non-inferiority margin suggesting that Ingovax ACWY is similar to Quadri MeningoTM vaccine. We observed the immunogenicity and safety of Ingovax ACWY is non-inferior to comparator vaccine. The development of facilities for manufacturing polysaccharide ACWY vaccines locally will further lead to capacity building in the field of vaccines for Bangladesh.
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Vacunas Meningococicas , Humanos , Vacunas Meningococicas/inmunología , Vacunas Meningococicas/administración & dosificación , Vacunas Meningococicas/efectos adversos , Adulto , Masculino , Femenino , Adulto Joven , Bangladesh , Persona de Mediana Edad , Adolescente , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Neisseria meningitidis/inmunología , Infecciones Meningocócicas/prevención & control , Infecciones Meningocócicas/inmunología , Vacunación/métodos , Inmunogenicidad Vacunal , Meningitis Meningocócica/prevención & control , Meningitis Meningocócica/inmunologíaRESUMEN
COVID-19, caused by SARS-CoV-2, and meningococcal disease, caused by Neisseria meningitidis, are relevant infectious diseases, preventable through vaccination. Outer membrane vesicles (OMVs), released from Gram-negative bacteria, such as N. meningitidis, present adjuvant characteristics and may confer protection against meningococcal disease. Here, we evaluated in mice the humoral and cellular immune response to different doses of receptor binding domain (RBD) of SARS-CoV-2 adjuvanted by N. meningitidis C:2a:P1.5 OMVs and aluminum hydroxide, as a combined preparation for these pathogens. The immunization induced IgG antibodies of high avidity for RBD and OMVs, besides IgG that recognized the Omicron BA.2 variant of SARS-CoV-2 with intermediary avidity. Cellular immunity showed IFN-γ and IL-4 secretion in response to RBD and OMV stimuli, demonstrating immunologic memory and a mixed Th1/Th2 response. Offspring presented transferred IgG of similar levels and avidity as their mothers. Humoral immunity did not point to the superiority of any RBD dose, but the group immunized with a lower antigenic dose (0.5 µg) had the better cellular response. Overall, OMVs enhanced RBD immunogenicity and conferred an immune response directed to N. meningitidis too.
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Anticuerpos Antivirales , COVID-19 , Inmunoglobulina G , Neisseria meningitidis , SARS-CoV-2 , Animales , Ratones , Inmunoglobulina G/sangre , Neisseria meningitidis/inmunología , Femenino , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , COVID-19/prevención & control , COVID-19/inmunología , SARS-CoV-2/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Inmunidad Celular , Inmunidad Humoral , Ratones Endogámicos BALB C , Infecciones Meningocócicas/prevención & control , Infecciones Meningocócicas/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Adyuvantes de Vacunas/administración & dosificación , Hidróxido de Aluminio/administración & dosificación , Hidróxido de Aluminio/inmunología , Inmunización/métodos , Afinidad de Anticuerpos , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Vacunas Meningococicas/inmunología , Vacunas Meningococicas/administración & dosificación , Memoria Inmunológica , Células TH1/inmunologíaRESUMEN
INTRODUCTION: Invasive meningococcal disease (IMD) is potentially fatal and associated with severe sequelae among survivors. It is preventable by several vaccines, including meningococcal vaccines targeting the most common disease-causing serogroups (A, B, C, W, Y). The meningococcal ACWY tetanus toxoid conjugate vaccine (MenACWY-TT [Nimenrix]) is indicated from 6 weeks of age in the European Union and >50 additional countries. AREAS COVERED: Using PubMed, Google Scholar, ClinicalTrials.gov and ad hoc searches for publications to June 2023, we review evidence of antibody persistence for up to 10 years after primary vaccination and up to 6 years after MenACWY-TT revaccination. We also review global MenACWY revaccination recommendations and real-world impact of vaccination policies, focusing on how these data can be considered alongside antibody persistence data to inform future IMD prevention strategies. EXPERT OPINION: Based on clear evidence that immunogenicity data (demonstrated antibody titers above established correlates of protection) are correlated with real-world effectiveness, long-term persistence of antibodies after MenACWY-TT vaccination suggests continuing protection against IMD. Optimal timing of primary and subsequent vaccinations is critical to maximize direct and indirect protection. Recommending bodies should carefully consider factors such as age at vaccination and long-term immune responses associated with the specific vaccine being used.
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Anticuerpos Antibacterianos , Inmunización Secundaria , Infecciones Meningocócicas , Vacunas Meningococicas , Humanos , Vacunas Meningococicas/inmunología , Vacunas Meningococicas/administración & dosificación , Infecciones Meningocócicas/prevención & control , Infecciones Meningocócicas/inmunología , Inmunización Secundaria/métodos , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Factores de Tiempo , Vacunación/métodosRESUMEN
The rates of nasopharyngeal meningococcal carriage in healthcare workers are unknown. Meningococcal vaccine is recommended for risk groups but healthcare workers are not included in risk groups for many countries. Herein, we aimed to investigate the nasopharyngeal meningococcal carriage rates, basal and after one dose of Men-ACWY-DT vaccine response on the 30th day by evaluating meningococcus IgG antibody levels and decolonization at month six after vaccination among the detected carriers. Nasopharyngeal swab samples were taken before vaccination to evaluate meningococcal carriage in healthcare workers. All participants received a single dose of Men-ACWY-DT vaccine. Serum samples were collected immediately before vaccination and again on day 30 post-vaccination. Antibodies in the stored sera were analyzed using the ELISA method. Participants who were determined to carry meningococci at the initial visit underwent another round of nasopharyngeal swab tests six months post-vaccination to check for decolonization. Between November 2020 and May 2021, we evaluated samples from 100 physicians [52 % females, 28.28 ± 4.45 (min: 24, max: 49)]. The majority of the physicians worked in the emergency department (45 %), followed by the infectious diseases clinic (14 %). Fifty-eight physicians had a history of at least one contact with a meningococcus-infected patient, and 53 (91.4 %) had used prophylactic antibiotics at least once due to this exposure. None of the study group nasopharyngeal swab cultures were positive for Neisseria meningitidis. Before the Men-ACWY-DT vaccine, anti-meningococcus IgG positivity was detected in the serum samples of only 3 (3 %) participants. By day 30 after vaccination, 48 % of participants showed positive for antibodies. As we didn't detect nasopharyngeal carriage in any participants, we didn't evaluate decolonization among carriers six months post-vaccination. Notably, detection of antibodies was evident in about half of the participants on day 30 after receiving a single dose of the Men-ACWY-DT vaccine.
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Anticuerpos Antibacterianos , Portador Sano , Personal de Salud , Infecciones Meningocócicas , Vacunas Meningococicas , Nasofaringe , Neisseria meningitidis , Humanos , Masculino , Vacunas Meningococicas/inmunología , Vacunas Meningococicas/administración & dosificación , Femenino , Portador Sano/inmunología , Portador Sano/microbiología , Adulto , Anticuerpos Antibacterianos/sangre , Infecciones Meningocócicas/prevención & control , Infecciones Meningocócicas/inmunología , Personal de Salud/estadística & datos numéricos , Neisseria meningitidis/inmunología , Nasofaringe/microbiología , Inmunoglobulina G/sangre , Vacunación/métodos , Adulto Joven , Formación de Anticuerpos/inmunología , Persona de Mediana EdadRESUMEN
Children with perinatally acquired HIV (PHIV) have special vaccination needs, as they make suboptimal immune responses. Here, we evaluated safety and immunogenicity of 2 doses of 4-component group B meningococcal vaccine in antiretroviral therapy-treated children with PHIV and healthy controls (HCs). Assessments included the standard human serum bactericidal antibody (hSBA) assay and measurement of IgG titers against capsular group B Neisseria meningitidis antigens (fHbp, NHBA, NadA). The B cell compartment and vaccine-induced antigen-specific (fHbp+) B cells were investigated by flow cytometry, and gene expression was investigated by multiplexed real-time PCR. A good safety and immunogenicity profile was shown in both groups; however, PHIV demonstrated a reduced immunogenicity compared with HCs. Additionally, PHIV showed a reduced frequency of fHbp+ and an altered B cell subset distribution, with higher fHbp+ frequency in activated memory and tissue-like memory B cells. Gene expression analyses on these cells revealed distinct mechanisms between PHIV and HC seroconverters. Overall, these data suggest that PHIV presents a diverse immune signature following vaccination. The impact of such perturbation on long-term maintenance of vaccine-induced immunity should be further evaluated in vulnerable populations, such as people with PHIV.
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Infecciones por VIH , Vacunas Meningococicas , Humanos , Infecciones por VIH/inmunología , Masculino , Femenino , Niño , Vacunas Meningococicas/inmunología , Vacunas Meningococicas/administración & dosificación , Preescolar , Infecciones Meningocócicas/inmunología , Infecciones Meningocócicas/prevención & control , Anticuerpos Antibacterianos/inmunología , Anticuerpos Antibacterianos/sangre , Linfocitos B/inmunología , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Inmunogenicidad Vacunal , Inmunoglobulina G/inmunología , Inmunoglobulina G/sangreRESUMEN
Invasive meningococcal disease (IMD) is caused by Neisseria meningitidis, with the main serogroups responsible for the disease being A, B, C, W, X, and Y. To date, several vaccines targeting N. meningitidis have been developed albeit with a short-lived protection. Given that MenW and MenB are the most common causes of IMD in Europe, Turkey, and the Middle East, we aimed to develop an outer membrane vesicle (OMV) based bivalent vaccine as the heterologous antigen source. Herein, we compared the immunogenicity, and breadth of serum bactericidal activity (SBA) assay-based protective coverage of OMV vaccine to the X serotype with existing commercial meningococcal conjugate and polysaccharide (PS) vaccines in a murine model. BALB/c mice were immunized with preclinical batches of the Wâ +â B OMV vaccine, either adjuvanted with Alum, CpG ODN, or their combinations, and compared with a MenACYW conjugate vaccine (NimenrixTM, Pfizer), and a MenB OMV-based vaccine (Bexsero®, GSK), The immune responses were assessed through enzyme-linked immunosorbent assay (ELISA) and SBA assay. Antibody responses and SBA titers were significantly higher in the Wâ +â B OMV vaccine when adjuvanted with Alum or CpG ODN, as compared to the control groups. Moreover, the SBA titers were not only significantly higher than those achieved with available conjugated ACYW vaccines but also on par with the 4CMenB vaccines. In conclusion, the Wâ +â B OMV vaccine demonstrated the capacity to elicit robust antibody responses, surpassing or matching the levels induced by licensed meningococcal vaccines. Consequently, the Wâ +â B OMV vaccine could potentially serve as a viable alternative or supplement to existing meningococcal vaccines.
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Compuestos de Alumbre , Infecciones Meningocócicas , Vacunas Meningococicas , Ratones Endogámicos BALB C , Neisseria meningitidis , Oligodesoxirribonucleótidos , Animales , Vacunas Meningococicas/inmunología , Vacunas Meningococicas/administración & dosificación , Ratones , Neisseria meningitidis/inmunología , Compuestos de Alumbre/administración & dosificación , Oligodesoxirribonucleótidos/inmunología , Oligodesoxirribonucleótidos/administración & dosificación , Femenino , Infecciones Meningocócicas/prevención & control , Infecciones Meningocócicas/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/farmacología , Anticuerpos Antibacterianos/inmunología , Anticuerpos Antibacterianos/sangre , Inmunogenicidad Vacunal , Membrana Externa Bacteriana/inmunologíaRESUMEN
Introducción: La principal medida de prevención frente a la enfermedad meningocócica invasiva es la vacunación. El objetivo de este estudio es evaluar la aceptabilidad y las desigualdades socioeconómicas en el acceso a la vacuna frente a meningococo B (MenB) en la Comunidad de Madrid en el periodo previo a la introducción de la misma en el calendario. Materiales y métodos: Se realizó un estudio observacional descriptivo en la cohorte de niños/as nacidos entre 2016 y 2019, de tipo ecológico, empleando registros poblacionales electrónicos. Se describieron las coberturas de vacunación, se analizaron los factores asociados al estado vacunal, se describieron las distribuciones espaciales de cobertura de vacunación y de índice de privación (IP) y se analizó la asociación entre ambas mediante regresión espacial. Resultados: Se observó una tendencia creciente de las coberturas de primovacunación, pasando de un 44% en la cohorte de nacidos en el año 2016 a un 68% en la cohorte de 2019. Se encontró asociación estadísticamente significativa entre el estado vacunal y el IP (OR de primovacunación en zonas con IP5 respecto a zonas con IP1: 0,38; IC 95%: 0,39-0,50; p<0,001). El análisis espacial mostró correlación inversa entre el IP y la cobertura de vacunación. Conclusiones: El ascenso de las coberturas de esta vacuna muestra aceptación por parte de la población. La relación entre nivel socioeconómico y cobertura de vacunación confirma la existencia de una desigualdad en salud, y subraya la importancia de su inclusión en el calendario.(AU)
Introduction: The main preventive measure against invasive meningococcal disease is vaccination. The aim of our study was to evaluate the acceptability of the meningococcal B (MenB) vaccine and socioeconomic inequalities in the access to the vaccine in the Community of Madrid in the period prior to its introduction in the immunization schedule. Materials and methods: We conducted an observational and ecological descriptive study in the cohort of children born between 2016 and 2019 using population-based electronic records. We calculated the vaccination coverage and analysed factors associated with vaccination status, determined the spatial distribution of vaccination coverage and the deprivation index (DI) and assessed the association between them by means of spatial regression. Results: We observed an increasing trend in primary vaccination coverage, from 44% in the cohort born in 2016 to 68% in the 2019 cohort. We found a statistically significant association between vaccination status and the DI (OR of primary vaccination in areas with DI5 compared to areas with DP1, 0.38; 95% confidence interval: 0.39-0.50; P<.001). The spatial analysis showed an inverse correlation between the DI and vaccination coverage. Conclusions: The rise in the coverages of the MenB vaccine shows acceptance by the population. The association between socioeconomic level and vaccination coverage confirms the existence of health inequality and underlines the importance including this vaccine in the immunization schedule.(AU)
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Humanos , Masculino , Femenino , Recién Nacido , Niño , Neisseria meningitidis Serogrupo B/inmunología , Meningitis Meningocócica/inmunología , Cobertura de Vacunación , Infecciones Meningocócicas/inmunología , España , Estudios de Cohortes , Epidemiología Descriptiva , Meningitis Meningocócica/prevención & control , Vacunación , Infecciones Meningocócicas/prevención & controlRESUMEN
INTRODUCTION: Meningococcal disease is associated with high mortality. When acute kidney injury (AKI) occurs in patients with severe meningococcal disease, it is typically attributable to sepsis, although meningococcal disease and lipopolysaccharide release are rarely investigated. Therefore, we evaluated renal tissue in a mouse model of meningococcal disease. METHODS: Female BALB/c mice were induced to AKI by meningococcal challenge. Markers of renal function were evaluated in infected and control mice. RESULTS: In the infected mice, serum concentrations of tumor necrosis factor alpha, interferon gamma, interleukins (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, and IL-12), and granulocyte-macrophage colony-stimulating factor were elevated, as was renal interstitial infiltration with lymphocytes and neutrophils (p < 0.01 for the latter). Histological analysis showed meningococcal microcolonies in the renal interstitium, without acute tubular necrosis. Infected mice also showed elevated renal expression of toll-like receptor 2, toll-like receptor 4, and Tamm-Horsfall protein. The expression of factors in the intrinsic pathway of apoptosis was equal to or lower than that observed in the control mice. Urinary sodium and potassium were also lower in infected mice, probably due to a tubular defect. CONCLUSION: Our findings corroborate those of other studies of AKI in sepsis. To our knowledge, this is the first time that meningococci have been identified in renal interstitium and that the resulting apoptosis and inflammation have been evaluated. However, additional studies are needed in order to elucidate the mechanisms involved.
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Lesión Renal Aguda , Riñón , Infecciones Meningocócicas , Neisseria meningitidis/aislamiento & purificación , Lesión Renal Aguda/sangre , Lesión Renal Aguda/etiología , Lesión Renal Aguda/inmunología , Lesión Renal Aguda/patología , Animales , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica/métodos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/análisis , Interleucinas/análisis , Riñón/inmunología , Riñón/microbiología , Riñón/patología , Infecciones Meningocócicas/complicaciones , Infecciones Meningocócicas/inmunología , Ratones , Ratones Endogámicos C57BL , Necrosis , Infiltración Neutrófila , Receptor Toll-Like 2/análisis , Receptor Toll-Like 4/análisis , Uromodulina/análisisRESUMEN
Dysregulation of complement activation causes a number of diseases, including paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. These conditions can be treated with monoclonal antibodies (mAbs) that bind to the complement component C5 and prevent formation of the membrane attack complex (MAC). While MAC is involved in uncontrolled lysis of erythrocytes in these patients, it is also required for serum bactericidal activity (SBA), i.e. clearance of encapsulated bacteria. Therefore, terminal complement blockage in these patients increases the risk of invasive disease by Neisseria meningitidis more than 1000-fold compared to the general population, despite obligatory vaccination. It is assumed that alternative instead of terminal pathway inhibition reduces the risk of meningococcal disease in vaccinated individuals. To address this, we investigated the SBA with alternative pathway inhibitors. Serum was collected from adults before and after vaccination with a meningococcal serogroup A, C, W, Y capsule conjugate vaccine and tested for meningococcal killing in the presence of factor B and D, C3, C5 and MASP-2 inhibitors. B meningococci were not included in this study since the immune response against protein-based vaccines is more complex. Unsurprisingly, inhibition of C5 abrogated killing of meningococci by all sera. In contrast, both factor B and D inhibitors affected meningococcal killing in sera from individuals with low, but not with high bactericidal anti-capsular titers. While the anti-MASP-2 mAb did not impair SBA, inhibition of C3 impeded meningococcal killing in most, but not in all sera. These data provide evidence that vaccination can provide protection against invasive meningococcal disease in patients treated with alternative pathway inhibitors.
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Anticuerpos Antibacterianos/inmunología , Inactivadores del Complemento/farmacología , Infecciones Meningocócicas/inmunología , Vacunas Meningococicas/inmunología , Adulto , Anciano , Vía Alternativa del Complemento/efectos de los fármacos , Femenino , Humanos , MasculinoRESUMEN
Cluster randomized trials (cRCT) to assess vaccine effectiveness incorporate indirect effects of vaccination, helping to inform vaccination policy. To calculate the sample size for a cRCT, an estimate of the intracluster correlation coefficient (ICC) is required. For infectious diseases, shared characteristics and social mixing behaviours may increase susceptibility and exposure, promote transmission and be a source of clustering. We present ICCs from a school-based cRCT assessing the effectiveness of a meningococcal B vaccine (Bexsero, GlaxoSmithKline) on reducing oropharyngeal carriage of Neisseria meningitidis (Nm) in 34,489 adolescents from 237 schools in South Australia in 2017/2018. We also explore the contribution of shared behaviours and characteristics to these ICCs. The ICC for carriage of disease-causing Nm genogroups (primary outcome) pre-vaccination was 0.004 (95% CI: 0.002, 0.007) and for all Nm was 0.007 (95%CI: 0.004, 0.011). Adjustment for social behaviours and personal characteristics reduced the ICC for carriage of disease-causing and all Nm genogroups by 25% (to 0.003) and 43% (to 0.004), respectively. ICCs are also reported for risk factors here, which may be outcomes in future research. Higher ICCs were observed for susceptibility and/or exposure variables related to Nm carriage (having a cold, spending ≥1 night out socializing or kissing ≥1 person in the previous week). In metropolitan areas, nights out socializing was a highly correlated behaviour. By contrast, smoking was a highly correlated behaviour in rural areas. A practical example to inform future cRCT sample size estimates is provided.
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Infecciones Meningocócicas/inmunología , Vacunas Meningococicas/inmunología , Neisseria meningitidis/inmunología , Adolescente , Análisis por Conglomerados , Femenino , Humanos , Masculino , Factores de Riesgo , Instituciones Académicas , Australia del Sur , VacunaciónRESUMEN
BACKGROUND: The incidence of invasive meningococcal disease due to serogroup C (MenC) decreased in Portugal since the introduction of the conjugate vaccine (MCC) in the free market in 2001 and in the National Immunisation Plan in 2006. Considering the potential waning of the antibody response reported in the literature, the different vaccination schemes that were used in our country over the past decade, and that Neisseria meningitidis serogroup C continues to circulate, the Portuguese population may currently be at increased risk of infection. In the absence of national data, we evaluated the seroprotection level of the Portuguese population against MenC, in order to identify the protected fraction of the population and ponder on the necessity of a booster dose of the MCC vaccine. METHODS: We measured serum bactericidal antibody levels against MenC in a representative sample of the population (n = 1500) aged 2-64 years who participated in the 2015/2016 National Serological Survey. RESULTS: A total of 31.1% (466/1500, 95%CI: 29-33%) of the individuals studied were protected against MenC. The geometric mean titre was 6.5. The proportion of seroprotected was particularly low in children aged 2-4 years (<16%) who received a single dose of the vaccine at 12 months of age (vaccination strategy since 2012). The proportion of seroprotected was higher (44.7% to 53.5%) in adolescent and young adults (15-24 years of age), resulting from vaccination during the catch-up campaign at 5-15 years of age. The highest protection rates were observed when the vaccine was administered during adolescence. CONCLUSION: The small fraction of population seroprotected, combined with the already known waning effect of the antibody response over time, may indicate that the Portuguese population will become progressively more exposed to the risk of infection. Taking in consideration our results, we recommend to change the current vaccination strategy and introduce a booster dose of the MCC vaccine during adolescence.
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Programas de Inmunización , Infecciones Meningocócicas/epidemiología , Vacunas Meningococicas/inmunología , Neisseria meningitidis Serogrupo C/inmunología , Adolescente , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Infecciones Meningocócicas/inmunología , Infecciones Meningocócicas/prevención & control , Portugal , Estudios Retrospectivos , Estudios Seroepidemiológicos , Adulto JovenRESUMEN
Neisseria meningitidis (N. meningitidis) is a human-specific pathogen and a major cause of meningitis and septicemia with a high case fatality rate. N. meningitidis may penetrate the nasopharyngeal mucosal membrane and cause severe meningitis, a mucosal immune response plays a key role in the defense against meningococcal infections. Our previous study demonstrated that N. meningitidis serogroup B 0315 (NMB0315) was a vaccine candidate against N. meningitidis serogroup B (NMB) through parenteral immunization. In this study, immunopotentiators (C48/80 or CpG-ODN) were loaded into chitosan nanoparticle (Chi NP) to form combination adjuvants (Chi-CpG NP and Chi-C48/80 NP) and adopted to enhance the immunogenicity of NMB0315 through intranasal immunization. The experimental results have indicated that both Chi-CpG NP and Chi-C48/80 NP are effective mucosal adjuvants for the induction of significantly higher rNMB0315-specific IgG, IgG1, IgG2a and sIgA antibodies. Meanwhile, Chi-CpG NP and Chi-C48/80 NP could change the ratio of IgG1/IgG2a, inducing a more balanced cellular/humoral immune response. Chi-CpG NP and Chi-C48/80 NP also boosted interleukin-4 (IL-4), interferon-γ (IFN-γ) and interleukin-17 A (IL-17A) production by splenocytes. The bactericidal antibodies have been detected in sera from mice immunized with rNMB0315 + Chi-CpG NP and rNMB0315 + Chi-C48/80 NP. Overall, the combination adjuvants could be applicable to the development of a mucosal vaccine against NMB.
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Antígenos Virales/administración & dosificación , Vacunas Bacterianas/inmunología , Infecciones Meningocócicas/inmunología , Nanopartículas/administración & dosificación , Neisseria meningitidis/inmunología , Adyuvantes Inmunológicos , Administración Intranasal , Animales , Antígenos Virales/química , Quitosano/química , Citocinas/metabolismo , Femenino , Humanos , Inmunidad , Inmunización , Ratones , Ratones Endogámicos BALB C , Nanopartículas/química , Serogrupo , VacunaciónRESUMEN
INTRODUCTION: Meningococcal vaccines to protect against invasive meningococcal disease (IMD) vary in terms of vaccine technology and serogroup coverage (Polysaccharide MnACWY, conjugated C and ACWY, outer membrane vesicle-based or protein-based B vaccines), and the national recommendations for each of them vary in terms of target population and number of doses. We sought to understand factors associated with the evolution of meningococcal vaccination program recommendations in four countries with formal evaluation processes: the UK, US, the Netherlands, and Canada. AREAS COVERED: A targeted review of published literature and internet sources for the four countries relating to meningococcal vaccination decision-making was conducted. The review focused on the impact of cost-effectiveness analyses on vaccine policy decisions and the extent to which variation in incidence of IMD and its potential catastrophic consequences influenced policy decisions.The evolution of meningococcal vaccine recommendations in the four countries was mainly driven by changes in vaccine availability and changes in serogroup incidence. Public pressure due to the catastrophic nature of IMD influenced recommendations. The role of cost-effectiveness analyses varied across the 4 countries. EXPERT OPINION: The value of implementing meningococcal vaccination programs should be assessed using factors beyond those included in traditional cost-effectiveness analyses.
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Infecciones Meningocócicas/prevención & control , Vacunas Meningococicas/administración & dosificación , Vacunación/métodos , Análisis Costo-Beneficio , Política de Salud , Humanos , Programas de Inmunización , Infecciones Meningocócicas/inmunología , Vacunas Meningococicas/economía , Vacunas Meningococicas/inmunología , Formulación de Políticas , Vacunación/economía , Vacunas ConjugadasRESUMEN
BACKGROUND: Neisseria meningitidis serogroup B remains a prominent cause of invasive meningococcal disease (IMD) in Brazil. Because two novel protein-based vaccines against serogroup B are available, the main purpose of this study was to provide data on the diversity and distribution of meningococcal vaccine antigen types circulating in Brazil. METHODOLOGY: Genetic lineages, vaccine antigen types, and allele types of antimicrobial-associated resistance genes based on whole-genome sequencing of a collection of 145 Neisseria meningitidis serogroup B invasive strains recovered in Brazil from 2016 to 2018 were collected. RESULTS: A total of 11 clonal complexes (ccs) were identified among the 145 isolates, four of which were predominant, namely, cc461, cc35, cc32, and cc213, accounting for 72.0% of isolates. The most prevalent fHbp peptides were 24 (subfamily A/variant 2), 47 (subfamily A/variant 3), 1 (subfamily B/variant 1) and 45 (subfamily A/variant 3), which were predominantly associated with cc35, cc461, cc32, and cc213, respectively. The NadA peptide was detected in only 26.2% of the isolates. The most frequent NadA peptide 1 was found almost exclusively in cc32. We found seven NHBA peptides that accounted for 74.5% of isolates, and the newly described peptide 1390 was the most prevalent peptide exclusively associated with cc461. Mutated penA alleles were detected in 56.5% of the isolates, whereas no rpoB and gyrA mutant alleles were found. CONCLUSION: During the study period, changes in the clonal structure of circulating strains were observed, without a predominance of a single hyperinvasive lineage, indicating that an epidemiologic shift has occurred that led to a diversity of vaccine antigen types in recent years in Brazil.
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Variación Genética/genética , Infecciones Meningocócicas/genética , Vacunas Meningococicas/genética , Neisseria meningitidis Serogrupo B/genética , Adolescente , Adulto , Anciano , Brasil/epidemiología , Niño , Preescolar , Femenino , Genoma Bacteriano/genética , Genómica , Humanos , Inmunogenicidad Vacunal/genética , Inmunogenicidad Vacunal/inmunología , Lactante , Masculino , Infecciones Meningocócicas/epidemiología , Infecciones Meningocócicas/inmunología , Vacunas Meningococicas/inmunología , Vacunas Meningococicas/uso terapéutico , Persona de Mediana Edad , Tipificación de Secuencias Multilocus/métodos , Neisseria meningitidis Serogrupo B/patogenicidad , Serogrupo , Secuenciación Completa del Genoma , Adulto JovenRESUMEN
Outer Membrane Vesicles (OMV) have received increased attention in recent years as a vaccine platform against bacterial pathogens. OMV from Neisseria meningitidis serogroup B have been extensively explored. Following the success of the MeNZB OMV vaccine in controlling an outbreak of N. meningitidis B in New Zealand, additional research and development resulted in the licensure of the OMV-containing four-component 4CMenB vaccine, Bexsero. This provided broader protection against multiple meningococcal B strains. Advances in the field of genetic engineering have permitted further improvements in the platform resulting in increased yields, reduced endotoxicity and decoration with homologous and heterologous antigens to enhance immuno genicity and provide broader protection. The OMV vaccine platform has been extended to many other pathogens. In this review, we discuss progress in the development of the OMV vaccine delivery platform, highlighting successful applications, together with potential challenges and gaps.