RESUMO
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.
Assuntos
Anticorpos Antivirais , COVID-19 , Imunoglobulina G , Neisseria meningitidis , SARS-CoV-2 , Animais , Camundongos , Imunoglobulina G/sangue , Neisseria meningitidis/imunologia , Feminino , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/prevenção & controle , COVID-19/imunologia , SARS-CoV-2/imunologia , Adjuvantes Imunológicos/administração & dosagem , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Imunidade Celular , Imunidade Humoral , Camundongos Endogâmicos BALB C , Infecções Meningocócicas/prevenção & controle , Infecções Meningocócicas/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adjuvantes de Vacinas/administração & dosagem , Hidróxido de Alumínio/administração & dosagem , Hidróxido de Alumínio/imunologia , Imunização/métodos , Afinidade de Anticorpos , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Vacinas Meningocócicas/imunologia , Vacinas Meningocócicas/administração & dosagem , Memória Imunológica , Células Th1/imunologiaRESUMO
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.
Assuntos
Injúria Renal Aguda , Rim , Infecções Meningocócicas , Neisseria meningitidis/isolamento & purificação , Injúria Renal Aguda/sangue , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/imunologia , Injúria Renal Aguda/patologia , Animais , Modelos Animais de Doenças , Perfilação da Expressão Gênica/métodos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/análise , Interleucinas/análise , Rim/imunologia , Rim/microbiologia , Rim/patologia , Infecções Meningocócicas/complicações , Infecções Meningocócicas/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Necrose , Infiltração de Neutrófilos , Receptor 2 Toll-Like/análise , Receptor 4 Toll-Like/análise , Uromodulina/análiseRESUMO
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.
Assuntos
Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/administração & dosagem , Vacinação/métodos , Análise Custo-Benefício , Política de Saúde , Humanos , Programas de Imunização , Infecções Meningocócicas/imunologia , Vacinas Meningocócicas/economia , Vacinas Meningocócicas/imunologia , Formulação de Políticas , Vacinação/economia , Vacinas ConjugadasRESUMO
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.
Assuntos
Variação Genética/genética , Infecções Meningocócicas/genética , Vacinas Meningocócicas/genética , Neisseria meningitidis Sorogrupo B/genética , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Genoma Bacteriano/genética , Genômica , Humanos , Imunogenicidade da Vacina/genética , Imunogenicidade da Vacina/imunologia , Lactente , Masculino , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/imunologia , Vacinas Meningocócicas/imunologia , Vacinas Meningocócicas/uso terapêutico , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus/métodos , Neisseria meningitidis Sorogrupo B/patogenicidade , Sorogrupo , Sequenciamento Completo do Genoma , Adulto JovemRESUMO
BACKGROUND: Invasive meningococcal disease is a major cause of meningitis in children. An investigational meningococcal (serogroups A, C, Y, and W) tetanus toxoid conjugate vaccine (MenACYW-TT) could offer protection against invasive meningococcal disease in this population. This phase III study assessed the immunogenicity and safety of MenACYW-TT in children compared with a licensed quadrivalent meningococcal vaccine conjugated with diphtheria protein CRM197 (MenACWY-CRM). METHODS: Healthy children 2-9 years of age in the United States, including Puerto Rico, were randomized (1:1) to receive MenACYW-TT (n = 499) or MenACWY-CRM (n = 501) (NCT03077438). Meningococcal antibody titers to the 4 vaccine serogroups were measured using a serum bactericidal antibody assay with human complement (hSBA) before and at day 30 after vaccination. Noninferiority between the vaccine groups was assessed by comparing seroresponse rates (postvaccination titers ≥1:16 when prevaccination titers were <1:8, or ≥4-fold increase if prevaccination titers were ≥1:8) to the 4 serogroups at day 30. Safety was monitored. RESULTS: The proportion of participants achieving seroresponse at day 30 in the MenACYW-TT group was noninferior to the MenACWY-CRM group (A: 55.4% vs. 47.8%; C: 95.2% vs. 47.8%; W: 78.8% vs. 64.1%; Y: 91.5% vs. 79.3%, respectively). Geometric mean titers for serogroups C, W, and Y were higher with MenACYW-TT than for MenACWY-CRM. Both vaccines were well-tolerated and had similar safety profiles. CONCLUSIONS: MenACYW-TT was well-tolerated in children and achieved noninferior immune responses to MenACWY-CRM against each of the 4 vaccine serogroups.
Assuntos
Imunogenicidade da Vacina , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/imunologia , Vacinas Combinadas/imunologia , Anticorpos Antibacterianos/sangue , Criança , Pré-Escolar , Método Duplo-Cego , Drogas em Investigação/administração & dosagem , Humanos , Infecções Meningocócicas/imunologia , Vacinas Meningocócicas/administração & dosagem , Neisseria meningitidis/imunologia , Porto Rico , Toxoide Tetânico/administração & dosagem , Toxoide Tetânico/imunologia , Estados Unidos , Vacinação , Vacinas Combinadas/administração & dosagem , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/imunologiaRESUMO
Meningococcal disease is a devastating infection caused by Neisseria meningitidis (meningococcus), and it is classified into serogroups according to its polysaccharide capsule composition. In Brazil, serogroup C is the most frequently responsible for the majority of cases, representing a serious public health challenge. In 2010, the meningococcal serogroup C conjugate vaccine was included in the calendar of the National Immunization Program. We have evaluated 163 meningococcal isolates collected during the pre (2006-2010) and post (2011-2016) vaccination periods. Epidemiological data were determined through Multilocus Sequence Typing (MLST) analysis, vaccine antigens and Bexsero Antigen Sequence Typing (BAST) variant. Clonal complex 103 remains the most prevalent in the country with a high number of serogroup C strains to which CC103 is directly associated. A total of 42 different ST were found. The two most prevalent ST were ST-3780 (CC103) with 38 strains and ST-10781, which was not associated with a CC with nine strains. Allele abcZ-276 was reported among 98% of the strains analyzed and it was not found among other CC103 strains worldwide, makes this allele an important genetic marker for a specific new clone only assigned to Brazilian serogroup C strains, ST-3780. FHbp-25 and NHBA-42 peptides were the most prevalent among isolates in both periods studied. BAST-824 and BAST-3073 have been expressed only in CC103 over the studied years, however, it was not possible to associate a BAST variant to a specific CC. Serogroup C phenotype [P1.22,14-6,36-2: F3-9: ST-3780 (CC103)] was the most prevalent according to the antigenic profiles of circulating strains in Brazil (2007-2016). Our study suggests that CC103 is still a major hypervirulent CC circulating in Brazil and ST-3780 is currently spreading all over the country even after the introduction of MenC in 2010.
Assuntos
Antígenos de Bactérias/genética , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/administração & dosagem , Tipagem de Sequências Multilocus/métodos , Neisseria meningitidis Sorogrupo C/classificação , Anticorpos Antibacterianos/metabolismo , Antígenos de Bactérias/imunologia , Brasil , Variação Genética , Humanos , Infecções Meningocócicas/imunologia , Vacinas Meningocócicas/genética , Vacinas Meningocócicas/imunologia , Neisseria meningitidis Sorogrupo C/genética , Neisseria meningitidis Sorogrupo C/imunologia , Neisseria meningitidis Sorogrupo C/isolamento & purificação , Filogenia , Vigilância da População , SorogrupoRESUMO
BACKGROUND: Serogroup causing invasive meningococcal disease (IMD) can change abruptly, as it occurred in Chile when serogroup predominance switched from MenB to MenW in 2012. As a response, a national vaccination strategy was implemented since 2012 using tetravalent meningococcal-conjugate vaccines (MCV-ACWY) in children 9â¯months through 4â¯years of age. The aim of this study was to describe IMD cases by MenW in Chile 2009-2016, and to analyse its trend after the introduction of MCV-ACWY. METHODS: Descriptive study of IMD cases in Chile, period 2009-2016. Cumulative incidence and mortality rate per 100,000 inhabitants, and case fatality rate (CRF) were used for descriptive analysis. Linear regression was used for post-intervention trend analysis. RESULTS: In 2012, MenW, mainly ST-11â¯cc, became predominant. MenW incidence rose from 0.01/100,000 inhabitants in 2009 to a maximum of 0.6/100,000 in 2015. Infants and adults 80â¯years of age and older were mostly affected, with an incidence peak of 9.7/100,000 and 1.6/100,000, respectively, in 2015. In the group of children from 1 to 4â¯years of age MenW incidence declined from 1.3/100,000 in 2012 to 0.1/100,000 in 2016, a 92.3% reduction after vaccination implementation. In the same period and age-cohort, CFR decreased from 23% to 0%. High mortality rates concentrated in infants and adults 80â¯years of age and over. CONCLUSION: MenW became predominant in Chile since 2012. IMD cases increased steadily from 2009 to 2016, with higher incidence, CFR and mortality concentrating in infants and people 80â¯years of age and older. MCV-ACWY provided direct protection against MenW, reducing its incidence after mass meningococcal vaccine implementation. Indirect effects of vaccination are not yet observed.
Assuntos
Infecções Meningocócicas/prevenção & controle , Vacinas Conjugadas/uso terapêutico , Adolescente , Adulto , Criança , Pré-Escolar , Chile/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Meningite Meningocócica/epidemiologia , Meningite Meningocócica/prevenção & controle , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/imunologia , Vacinas Meningocócicas/uso terapêutico , Pessoa de Meia-Idade , Neisseria meningitidis/imunologia , Neisseria meningitidis/patogenicidade , Sorogrupo , Vacinação/estatística & dados numéricos , Adulto JovemRESUMO
Vaccination has reduced morbidity and mortality of many diseases that previously caused devastating epidemics and deaths globally. Vaccines as a biological product may contain microorganisms or their derivatives. This aspect together with the fact that they are administered to healthy individuals (mainly children) means that approximately 70% of vaccines development time is dedicated to quality control. Monoclonal antibodies (MAbs) have become essential analytical tools for application in ELISAs, Western and Dot blotting, immunoprecipitation, and flow cytometric assays that ensure the quality control of vaccines. The aim of this work is to present a review of the methods used to obtain a platform of MAbs against Neisseria meningitidis polysaccharide antigens to use as an analytical tool for quality control of anti-meningococcal polysaccharide (Ps) vaccines. The MAbs obtained are used in five sandwich ELISAs developed for Ps quantification. The assays showed good reproducibility and repeatability, with quantitation and detection limits below 1 ng/mL. Dot Blot, as the Identity test of the Ps vaccine, was carried out to positively identify licensed and experimental vaccines. All assays described are suitable for the screening of multiple vaccine samples and could be useful for monitoring lot-to-lot consistency and stability.
Assuntos
Anticorpos Antibacterianos/imunologia , Anticorpos Monoclonais/imunologia , Infecções Meningocócicas/imunologia , Vacinas Meningocócicas/normas , Neisseria meningitidis/imunologia , Polissacarídeos Bacterianos/imunologia , Controle de Qualidade , Humanos , Infecções Meningocócicas/microbiologia , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/administração & dosagem , Polissacarídeos Bacterianos/classificaçãoRESUMO
BACKGROUND: Meningococcal disease (MD) is a major cause of meningitis and sepsis worldwide, with a high case fatality rate and frequent sequelae. Neisseria meningitidis serogroups A, B, C, W, X and Y are responsible for most of these life-threatening infections, and its unpredictable epidemiology can cause outbreaks in communities, with significant health, social and economic impact. Currently, serogroup B is the main cause of MD in Europe and North America and one of the most prevalent serogroups in Latin America. Mass vaccination strategies using polysaccharide vaccines have been deployed since the 1970s and the use of conjugate vaccines has controlled endemic and epidemic disease caused by serogroups A, C, W and Y and more recently serogroup B using geographically-specific outer membrane vesicle based vaccines. Two novel protein-based vaccines are a significant addition to our armamentarium against N. meningitidis as they provide broad coverage against highly diverse strains in serogroup B and other groups. Early safety, effectiveness and impact data of these vaccines are encouraging. These novel serogroup B vaccines should be actively considered for individuals at increased risk of disease and to control serogroup B outbreaks occurring in institutions or specific regions, as they are likely to save lives and prevent severe sequelae. Incorporation into national programs will require thorough country-specific analysis.