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1.
Clin Infect Dis ; 68(3): 435-443, 2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-30481265

RESUMO

Background: In Burkina Faso, serogroup A meningococcal (NmA) conjugate vaccine (PsA-TT, MenAfriVac) was introduced through a mass campaign in children and adults in December 2010. Similar to a serological survey in 2011, we followed population-level antibody persistence for 5 years after the campaign and estimated time of return to previously-published pre-vaccination levels. Methods: We conducted 2 cross-sectional surveys in 2013 and early 2016, including representative samples (N = 600) of the general population of Bobo-Dioulasso, Burkina Faso. Serum bactericidal antibody titers (rabbit complement) were measured against NmA reference strain F8236 (SBA-ref), NmA strain 3125 (SBA-3125), and NmA-specific immunoglobulin G (IgG) concentrations. Results: During the 2016 survey, in different age groups between 6 and 29 years, the relative changes in geometric means compared to 2011 values were greater among younger age groups. They were between -87% and -43% for SBA-ref; -99% and -78% for SBA-3125; and -89% and -63% for IgG. In linear extrapolation of age-specific geometric means from 2013 to 2016, among children aged 1-4 years at the time of the PsA-TT campaign, a return to pre-vaccination levels should be expected after 12, 8, and 6 years, respectively, according to SBA-ref, SBA-3125, and IgG. Among older individuals, complete return to baseline is expected at the earliest after 11 years (SBA-ref and SBA-3125) or 9 years (IgG). Conclusions: Based on SBA-3125, a booster campaign after 8 years would be required to sustain direct immune protection for children aged 1-4 years during the PsA-TT campaign. Antibodies persisted longer in older age groups.


Assuntos
Anticorpos Antibacterianos/sangue , Vacinação em Massa , Infecções Meningocócicas/imunologia , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/imunologia , Neisseria meningitidis Sorogrupo A/imunologia , Adolescente , Adulto , Animais , Burkina Faso , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Imunoglobulina G/sangue , Lactente , Masculino , Vacinas Meningocócicas/administração & dosagem , Coelhos , Fatores de Tempo , Adulto Jovem
2.
Euro Surveill ; 24(1)2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30621818

RESUMO

BackgroundIn 1999, the United Kingdom (UK) was the first country to introduce meningococcal group C (MenC) conjugate vaccination. This vaccination programme has evolved with further understanding, new vaccines and changing disease epidemiology.AimTo characterise MenC disease and population protection against MenC disease in England.MethodsBetween 1998/99-2015/16, surveillance data from England for laboratory-confirmed MenC cases were collated; using the screening method, we updated vaccine effectiveness (VE) estimates. Typing data and genomes were obtained from the Meningitis Research Foundation Meningococcus Genome Library and PubMLST Neisseria database. Phylogenetic network analysis of MenC cc11 isolates was undertaken. We compared bactericidal antibody assay results using anonymised sera from 2014 to similar data from 1996-1999, 2000-2004 and 2009.ResultsMenC cases fell from 883 in 1998/99 (1.81/100,000 population) to 42 cases (0.08/100,000 population) in 2015/16. Lower VE over time since vaccination was observed after infant immunisation (p = 0.009) and a single dose at 1-4 years (p = 0.03). After vaccination at 5-18 years, high VE was sustained for ≥ 8 years; 95.0% (95% CI: 76.0- 99.5%). Only 25% (75/299) children aged 1-14 years were seroprotected against MenC disease in 2014. Recent case isolates mostly represented two cc11 strains.ConclusionHigh quality surveillance has furthered understanding of MenC vaccines and improved schedules, maximising population benefit. The UK programme provides high direct and indirect protection despite low levels of seroprotection in some age groups. High-resolution characterisation supports ongoing surveillance of distinct MenC cc11 lineages.


Assuntos
Meningite Meningocócica/epidemiologia , Infecções Meningocócicas/epidemiologia , Vacinas Meningocócicas/imunologia , Neisseria meningitidis Sorogrupo C/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Inglaterra/epidemiologia , Feminino , Humanos , Programas de Imunização , Incidência , Lactente , Masculino , Meningite Meningocócica/prevenção & controle , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/administração & dosagem , Neisseria meningitidis Sorogrupo C/isolamento & purificação , Estudos Soroepidemiológicos , Vacinação , Adulto Jovem
3.
Clin Infect Dis ; 61 Suppl 5: S563-9, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26553689

RESUMO

BACKGROUND: A group A meningococcal conjugate vaccine, PsA-TT, was licensed in 2010 and was previously studied in a phase 2 clinical trial to evaluate its safety and immunogenicity in African children 12-23 months of age. METHODS: Subjects received either PsA-TT; meningococcal group A, C, W, Y polysaccharide vaccine (PsACWY); or Haemophilus influenzae type b conjugate vaccine (Hib-TT). Forty weeks following primary vaccination, the 3 groups were further randomized to receive either PsA-TT, one-fifth dose of PsACWY, or Hib-TT. Group A-specific immunoglobulin G (IgG) subclass response was characterized using an enzyme-linked immunosorbent assay. RESULTS: The predominant IgG subclass response, regardless of vaccine, was IgG1. One month following primary vaccination, the geometric mean concentrations (GMCs) of IgG1 and IgG2 in the PsA-TT group were 21.73 µg/mL and 6.27 µg/mL, whereas in the PsACWY group the mean GMCs were 2.01 µg/mL and 0.97 µg/mL, respectively (P < .0001). Group A-specific IgG1 and IgG2 GMCs remained greater in the PsA-TT group than in the PsACWY group 40 weeks following primary vaccination (P < .0001). One week following revaccination, those given 2 doses of PsA-TT had the greatest IgG1 and IgG2 GMCs of 125.23 µg/mL and 36.12 µg/mL, respectively (P = .0008), and demonstrated a significant increase in IgG1:IgG2 mean ratio, indicative of the T-cell-dependent response associated with conjugate vaccines. CONCLUSIONS: Vaccination of African children aged 12-24 months with either PsA-TT or PsACWY elicited a predominantly IgG1 response. The IgG1:IgG2 mean ratio decreased following successive vaccination with PsACWY, indicating a shift toward IgG2, suggestive of the T-cell-independent immune response commonly associated with polysaccharide antigens. CLINICAL TRIALS REGISTRATION: SRCTN78147026.


Assuntos
Anticorpos Antibacterianos/sangue , Imunoglobulina G/sangue , Vacinas Meningocócicas/administração & dosagem , Vacinas Meningocócicas/imunologia , Neisseria meningitidis Sorogrupo A/imunologia , África , Ensaio de Imunoadsorção Enzimática , Feminino , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/imunologia , Humanos , Lactente , Masculino , Toxoide Tetânico/administração & dosagem , Toxoide Tetânico/imunologia
4.
Clin Infect Dis ; 61(11): 1637-44, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26374816

RESUMO

INTRODUCTION: In England, antenatal pertussis immunization using a tetanus/low-dose diphtheria/5-component acellular-pertussis/inactivated-polio (TdaP5/IPV) vaccine was introduced in October 2012. We assessed infant responses to antigens in the maternal vaccine and to those conjugated to tetanus (TT) or the diphtheria toxin variant, CRM. METHODS: Infants of 141 TdaP5/IPV-vaccinated mothers in Southern England immunized with DTaP5/IPV/Haemophilus influenzae b (Hib-TT) vaccine at 2-3-4 months, 13-valent pneumococcal vaccine (PCV13, CRM-conjugated) at 2-4 months and 1 or 2 meningococcal C vaccine (MCC-CRM- or MCC-TT) doses at 3-4 months had blood samples taken at 2 and/or 5 months of age. RESULTS: Antibody responses to pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbriae 2 + 3 (FIMs), diphtheria, tetanus, Hib, MCC and PCV13 serotypes were compared to responses in a historical cohort of 246 infants born to mothers not vaccinated in pregnancy. Infants had high pertussis antibody concentrations pre-immunization but only PT antibodies increased post-immunization (fold-change, 2.64; 95% confidence interval [CI], 2.12-3.30; P < .001), whereas FHA antibodies fell (fold-change, 0.56; 95% CI, .48-.65; P < .001). Compared with infants of unvaccinated mothers, PT, FHA, and FIMs antibodies were lower post-vaccination, with fold-differences of 0.67 (0.58-0.77; P < .001), 0.62 (0.54-0.71; P < .001) and 0.51 (0.42-0.62; P < .001), respectively. Antibodies to diphtheria and some CRM-conjugated antigens were also lower, although most infants achieved protective thresholds; antibodies to tetanus and Hib were higher. CONCLUSIONS: Antenatal pertussis immunization results in high infant pre-immunization antibody concentrations, but blunts subsequent responses to pertussis vaccine and some CRM-conjugated antigens. In countries with no pertussis booster until school age, continued monitoring of protection against pertussis is essential.


Assuntos
Anticorpos Antibacterianos/sangue , Bordetella pertussis/imunologia , Vacinas contra Difteria, Tétano e Coqueluche Acelular/imunologia , Imunidade Materno-Adquirida , Coqueluche/imunologia , Antígenos de Bactérias/imunologia , Estudos de Coortes , Vacinas contra Difteria, Tétano e Coqueluche Acelular/administração & dosagem , Inglaterra , Feminino , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/imunologia , Humanos , Imunização Secundária , Imunoglobulina G/sangue , Lactente , Masculino , Vacinas Meningocócicas/administração & dosagem , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/imunologia , Vacina Antipólio de Vírus Inativado/administração & dosagem , Gravidez , Toxoide Tetânico/administração & dosagem , Toxoide Tetânico/imunologia , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/imunologia , Coqueluche/prevenção & controle
5.
Clin Infect Dis ; 61 Suppl 5: S547-53, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26553687

RESUMO

BACKGROUND: In 2010, Africa's first preventive meningococcal mass vaccination campaign was launched using a newly developed Neisseria meningitidis group A (NmA) polysaccharide-tetanus toxoid conjugate vaccine, PsA-TT (MenAfriVac), designed specifically for the meningitis belt. Given PsA-TT's recent introduction, the duration of protection against meningococcal group A is unknown. METHODS: We conducted a household-based, age-stratified seroprevalence survey in Bamako, Mali, in 2012, 2 years after the vaccination campaign targeted all 1- to 29-year-olds. Randomly selected participants who had been eligible for PsA-TT provided a blood sample and responded to a questionnaire. Sera were analyzed to assess NmA-specific serum bactericidal antibody titers using rabbit complement (rSBA) and NmA-specific immunoglobulin G (IgG) by enzyme-linked immunosorbent assay. The proportion of participants putatively protected and the age group- and sex-specific rSBA geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) were determined. RESULTS: Two years postvaccination, nearly all of the 800 participants (99.0%; 95% confidence interval [CI], 98.3%-99.7%) maintained NmA-specific rSBA titers ≥8, the accepted threshold for protection; 98.6% (95% CI, 97.8%-99.4%) had titers ≥128, and 89.5% (95% CI, 87.4%-91.6%) had titers ≥1024. The rSBA GMTs were significantly higher in females than in males aged <18 years at vaccination (P < .0001). NmA-specific IgG levels ≥2 µg/mL were found in 88.5% (95% CI, 86.3%-90.7%) of participants. CONCLUSIONS: Two years after PsA-TT introduction, a very high proportion of the population targeted for vaccination maintains high antibody titers against NmA. Assessing the duration of protection provided by PsA-TT is a priority for implementing evidence-based vaccination strategies. Representative, population-based seroprevalence studies complement clinical trials and provide this key evidence.


Assuntos
Anticorpos Antibacterianos/sangue , Meningite Meningocócica/prevenção & controle , Vacinas Meningocócicas/imunologia , Neisseria meningitidis Sorogrupo A/imunologia , Adolescente , Adulto , Animais , Atividade Bactericida do Sangue , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Lactente , Masculino , Mali/epidemiologia , Meningite Meningocócica/epidemiologia , Vacinas Meningocócicas/administração & dosagem , Estudos Soroepidemiológicos , Inquéritos e Questionários , Fatores de Tempo , Adulto Jovem
6.
Clin Infect Dis ; 61 Suppl 5: S540-6, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26553686

RESUMO

BACKGROUND: A group A meningococcal (MenA) conjugate vaccine, PsA-TT (MenAfriVac), was introduced in Burkina Faso via mass campaigns between September and December 2010, targeting the 1- to 29-year-old population. This study describes specific antibody titers in the general population 11 months later and compares them to preintroduction data obtained during 2008 using the same protocol. METHODS: During October-November 2011, we recruited a representative sample of the population of urban Bobo-Dioulasso aged 6 months to 29 years, who underwent standardized interviews and blood draws. We assessed anti-MenA immunoglobulin G (IgG) concentrations (n = 200) and, using rabbit complement, serum bactericidal antibody (SBA) titers against 2 group A strains: reference strain F8238 (SBAref) (n = 562) and strain 3125 (SBA3125) (n = 200). RESULTS: Among the 562 participants, 481 (86%) were aged ≥23 months and had been eligible for the PsA-TT campaign. Among them, vaccine coverage was 86.3% (95% confidence interval [CI], 82.7%-89.9%). Prevalence of putatively protective antibodies among vaccine-eligible age groups was 97.3% (95% CI, 95.9%-98.7%) for SBAref titers ≥128, 83.6% (95% CI, 77.6%-89.7%) for SBA3125 ≥128, and 84.2% (95% CI, 78.7%-89.7%) for anti-MenA IgG ≥2 µg/mL. Compared to the population aged 23 months to 29 years during 2008, geometric mean titers of SBAref were 7.59-fold higher during 2011, 51.88-fold for SBA3125, and 10.56-fold for IgG. CONCLUSIONS: This study shows high seroprevalence against group A meningococci in Burkina Faso following MenAfriVac introduction. Follow-up surveys will provide evidence on the persistence of population-level immunity and the optimal vaccination strategy for long-term control of MenA meningitis in the African meningitis belt.


Assuntos
Anticorpos Antibacterianos/sangue , Vacinação em Massa , Meningite Meningocócica/prevenção & controle , Vacinas Meningocócicas/administração & dosagem , Vacinas Meningocócicas/imunologia , Neisseria meningitidis Sorogrupo A/imunologia , Adolescente , Adulto , Animais , Atividade Bactericida do Sangue , Burkina Faso , Criança , Pré-Escolar , Proteínas do Sistema Complemento , Feminino , Humanos , Imunoglobulina G/sangue , Lactente , Masculino , Coelhos , Estudos Soroepidemiológicos , Adulto Jovem
7.
Clin Infect Dis ; 61 Suppl 5: S554-62, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26553688

RESUMO

BACKGROUND: PsA-TT (MenAfriVac) is a conjugated polysaccharide vaccine developed to eliminate group A meningococcal disease in Africa. Vaccination of African study participants with 1 dose of PsA-TT led to the production of anti-A polysaccharide antibodies and increased serum bactericidal activity measured using rabbit complement (rSBA). Bactericidal responses measured with human complement (hSBA) are presented here. METHODS: Sera collected before and at 28 days and 1 year after vaccination with either PsA-TT or quadrivalent polysaccharide vaccine (PsACWY) from a random, age-distributed 360-subject subset of the Meningitis Vaccine Project study of PsA-TT in Africans aged 2-29 years were tested for hSBA. Geometric mean titer, fold-rise, and threshold analyses were compared between vaccine groups and age groups. hSBA, rSBA, and immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) results were compared and assay correlation and agreement determined. RESULTS: hSBA responses to PsA-TT were substantially higher than those to PsACWY at 28 days and 1 year following immunization, similar to previously reported rSBA and IgG results. The hSBA and IgG ELISA results identified differences between age groups that were not evident by rSBA. The rSBA data indicated sustained high titers 1 year after immunization, whereas hSBA GMTs at 1 year approached 4 in young children. CONCLUSIONS: The high level of protection following PsA-TT immunization campaigns is consistent with the strong hSBA immune responses observed here. Future implementation decisions will likely depend on immunologic data and their long-term correlation with disease and carriage prevention. Expanded immunologic and epidemiologic surveillance may improve the interpretation of differences between these immunoassays.


Assuntos
Anticorpos Antibacterianos/sangue , Atividade Bactericida do Sangue , Proteínas do Sistema Complemento , Imunoensaio/métodos , Vacinas Meningocócicas/imunologia , Neisseria meningitidis Sorogrupo A/imunologia , Adolescente , Adulto , África , Animais , Criança , Pré-Escolar , Humanos , Imunoglobulina G/sangue , Vacinas Meningocócicas/administração & dosagem , Coelhos , Adulto Jovem
8.
Clin Infect Dis ; 61 Suppl 5: S514-20, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26553683

RESUMO

BACKGROUND: Following mass vaccination campaigns in the African meningitis belt with group A meningococcal conjugate vaccine, MenAfriVac (PsA-TT), disease due to group A meningococci has nearly disappeared. Antibody persistence in healthy African toddlers was investigated. METHODS: African children vaccinated at 12-23 months of age with PsA-TT were followed for evaluation of antibody persistence up to 5 years after primary vaccination. Antibody persistence was evaluated by measuring group A serum bactericidal antibody (SBA) with rabbit complement and by a group A-specific IgG enzyme-linked immunosorbent assay (ELISA). RESULTS: Group A antibodies measured by SBA and ELISA were shown to decline in the year following vaccination and plateaued at levels significantly above baseline for up to 5 years following primary vaccination. CONCLUSIONS: A single dose of PsA-TT induces long-term sustained levels of group A meningococcal antibodies for up to 5 years after vaccination. CLINICAL TRIALS REGISTRATION: ISRTCN78147026.


Assuntos
Anticorpos Antibacterianos/sangue , Atividade Bactericida do Sangue , Vacinas Meningocócicas/administração & dosagem , Vacinas Meningocócicas/imunologia , África , Animais , Proteínas do Sistema Complemento , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Imunoglobulina G/sangue , Lactente , Masculino , Coelhos , Fatores de Tempo
9.
Clin Infect Dis ; 61 Suppl 5: S521-30, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26553684

RESUMO

BACKGROUND: Mass vaccination campaigns of the population aged 1-29 years with 1 dose of group A meningococcal (MenA) conjugate vaccine (PsA-TT, MenAfriVac) in African meningitis belt countries has resulted in the near-disappearance of MenA. The vaccine was tested in clinical trials in Africa and in India and found to be safe and highly immunogenic compared with the group A component of the licensed quadrivalent polysaccharide vaccine (PsACWY). Antibody persistence in Africa and in India was investigated. METHODS: A total of 900 subjects aged 2-29 years were followed up for 4 years in Senegal, Mali, and The Gambia (study A). A total of 340 subjects aged 2-10 years were followed up for 1 year in India (study B). In study A, subjects were randomized in a 2:1 ratio, and in study B a 1:1 ratio to receive either PsA-TT or PsACWY. Immunogenicity was evaluated by measuring MenA serum bactericidal antibody (SBA) with rabbit complement and by a group A-specific immunoglobulin G (IgG) enzyme-linked immunosorbent assay. RESULTS: In both studies, substantial SBA decay was observed at 6 months postvaccination in both vaccine groups, although more marked in the PsACWY group. At 1 year and 4 years (only for study A) postvaccination, SBA titers were relatively sustained in the PsA-TT group, whereas a slight increasing trend, more pronounced among the youngest, was observed in the participants aged <18 years in the PsACWY groups. The SBA titers were significantly higher in the PsA-TT group than in the PsACWY group at any time point, and the majority of subjects in the PsA-TT group had SBA titers ≥128 and group A-specific IgG concentrations ≥2 µg/mL at any point in time in both the African and Indian study populations. CONCLUSIONS: Four years after vaccination with a single dose of PsA-TT vaccine in Africa, most subjects are considered protected from MenA disease. CLINICAL TRIALS REGISTRATION: PsA-TT-003 (ISRCTN87739946); PsA-TT-003a (ISRCTN46335400).


Assuntos
Anticorpos Antibacterianos/sangue , Atividade Bactericida do Sangue , Vacinas Meningocócicas/administração & dosagem , Vacinas Meningocócicas/imunologia , Adolescente , Adulto , África , Animais , Criança , Pré-Escolar , Proteínas do Sistema Complemento , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Voluntários Saudáveis , Humanos , Índia , Masculino , Coelhos , Fatores de Tempo , Adulto Jovem
10.
N Engl J Med ; 364(24): 2293-304, 2011 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-21675889

RESUMO

BACKGROUND: Group A meningococci are the source of major epidemics of meningitis in Africa. An affordable, highly immunogenic meningococcal A conjugate vaccine is needed. METHODS: We conducted two studies in Africa to evaluate a new MenA conjugate vaccine (PsA-TT). In study A, 601 children, 12 to 23 months of age, were randomly assigned to receive PsA-TT, a quadrivalent polysaccharide reference vaccine (PsACWY), or a control vaccine (Haemophilus influenzae type b conjugate vaccine [Hib-TT]). Ten months later, these children underwent another round of randomization within each group to receive a full dose of PsA-TT, a one-fifth dose of PsACWY, or a full dose of Hib-TT, with 589 of the original participants receiving a booster dose. In study B, 900 subjects between 2 and 29 years of age were randomly assigned to receive PsA-TT or PsACWY. Safety and reactogenicity were evaluated, and immunogenicity was assessed by measuring the activity of group A serum bactericidal antibody (SBA) with rabbit complement and performing an IgG group A-specific enzyme-linked immunosorbent assay. RESULTS: In study A, 96.0% of the subjects in the PsA-TT group and 63.7% of those in the PsACWY group had SBA titers that were at least four times as high as those at baseline; in study B, 78.2% of the subjects in the PsA-TT group and 46.2% of those in the PsACWY group had SBA titers that were at least four times as high as those at baseline. The geometric mean SBA titers in the PsA-TT groups in studies A and B were greater by factors of 16 and 3, respectively, than they were in the PsACWY groups (P<0.001). In study A, the PsA-TT group had higher antibody titers at week 40 than the PsACWY group and had obvious immunologic memory after receiving a polysaccharide booster vaccine. Safety profiles were similar across vaccine groups, although PsA-TT recipients were more likely than PsACWY recipients to have tenderness and induration at the vaccination site. Adverse events were consistent with age-specific morbidity in the study areas; no serious vaccine-related adverse events were reported. CONCLUSIONS: The PsA-TT vaccine elicited a stronger response to group A antibody than the PsACWY vaccine. (Funded by the Meningitis Vaccine Project through a grant from the Bill and Melinda Gates Foundation; Controlled-Trials.com numbers, ISRCTN78147026 and ISRCTN87739946.).


Assuntos
Anticorpos Antibacterianos/sangue , Vacinas Meningocócicas/imunologia , Neisseria meningitidis/imunologia , África , Método Duplo-Cego , Feminino , Vacinas Anti-Haemophilus , Humanos , Memória Imunológica , Lactente , Masculino , Vacinas Meningocócicas/efeitos adversos , Polissacarídeos Bacterianos , Toxoide Tetânico , Vacinas Conjugadas/efeitos adversos , Vacinas Conjugadas/imunologia
11.
Clin Infect Dis ; 52(11): 1317-23, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21596673

RESUMO

BACKGROUND: Recipients of serogroup-C glycoconjugate meningococcal vaccine (MCC) exhibit waning of serum bactericidal antibody (SBA) titers, but the rate of decline and the speed of their immunological memory in response to new meningococcal nasopharyngeal colonization are unknown. METHODS: In a prospective challenge study, we measured persistence of SBA and anti-Neisseria meningitidis serogroup-C (MenC) immunoglobulin (Ig) G and IgA in adults aged 18-39, 28 days and 12 months after receiving MCC. Volunteers were then challenged intranasally with 50 µg MenC polysaccharide to mimic meningococcal colonization, and systemic and mucosal antibody responses were measured. RESULTS: All subjects had protective SBA titers (≥8) 28 days after MCC vaccination, but 12.3% and 20.2% had unprotective (<8) or low (<128) levels, respectively, after 12 months. Following rechallenge (12 months postvaccination) and measurement of antibody responses after 4, 7, and 10 days, rises in SBA titers were only observed in subjects with low (<128) or nonprotective (<8) prerechallenge SBA titers. In subjects with pre rechallenge SBA titers <8, the majority did not reach a protective SBA titer until 7 days post-rechallenge. MenC-specific IgG levels rose in both serum and saliva in correlation with SBA titers. No detectable rise in salivary IgA was observed. CONCLUSIONS: In those individuals who fail to retain protective SBA 12 months after MCC, immunological memory fails to generate protective systemic and mucosal antibodies until 7 days post intranasal challenge with cognate meningococcal polysaccharide. This is likely too slow to protect from natural meningococcal infection. MCC vaccinees rely on persistence of antibody levels rather than immunological memory for sustained protection.


Assuntos
Anticorpos Antibacterianos/sangue , Vacinas Meningocócicas/imunologia , Mucosa Nasal/imunologia , Neisseria meningitidis Sorogrupo C/imunologia , Polissacarídeos Bacterianos/imunologia , Adolescente , Adulto , Atividade Bactericida do Sangue , Humanos , Imunoglobulina A/análise , Imunoglobulina G/sangue , Vacinas Meningocócicas/administração & dosagem , Estudos Prospectivos , Fatores de Tempo , Adulto Jovem
12.
Lancet Infect Dis ; 21(5): 688-696, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33428870

RESUMO

BACKGROUND: The use of the multicomponent meningococcal vaccine 4CMenB in the UK schedule at 2, 4, and 12 months of age has been shown to be 59·1% effective at preventing invasive group B meningococcal disease. Here, we report the first data on the immunogenicity of this reduced-dose schedule to help to interpret this effectiveness estimate. METHODS: In this multicentre, parallel-group, open-label, randomised clinical trial, infants aged up to 13 weeks due to receive their primary immunisations were recruited via child health database mailouts in Oxfordshire and via general practice surgeries in Gloucestershire and Hertfordshire. Infants were randomly assigned (1:1) with permuted block randomisation to receive a 2 + 1 (2, 4, and 12 months; group 1) or 1 + 1 (3 and 12 months; group 2) schedule of the 13-valent pneumococcal conjugate vaccine (PCV13). All infants also received 4CMenB at 2, 4, and 12 months of age, and had blood samples taken at 5 and 13 months. Participants and clinical trial staff were not masked to treatment allocation. Proportions of participants with human complement serum bactericidal antibody (hSBA) titres of at least 4 were determined for group B meningococcus (MenB) reference strains 5/99 (Neisserial Adhesin A [NadA]), NZ98/254 (porin A), and 44/76-SL (factor H binding protein [fHbp]). Geometric mean titres (GMTs) with 95% CIs were also calculated, and concomitant vaccine responses (group C meningococcus [MenC], Haemophilus influenzae b [Hib], tetanus, diphtheria, and pertussis) were compared between groups. The primary outcome was PCV13 immunogenicity, with 4CMenB immunogenicity and reactogenicity as secondary outcomes. All individuals by randomised group with a laboratory result were included in the analysis. The study is registered on the EudraCT clinical trials database, 2015-000817-32, and ClinicalTrials.gov, NCT02482636, and is complete. FINDINGS: Between Sept 22, 2015, and Nov 1, 2017, of 376 infants screened, 213 were enrolled (106 in group 1 and 107 in group 2). 204 samples post-primary immunisation and 180 post-boost were available for analysis. The proportion of participants with hSBA of at least 4 was similar in the two study groups. For strain 5/99, all participants developed hSBA titres above 4 in both groups and at both timepoints. For strain 44/76-SL, these proportions were 95·3% (95% CI 88·5-98·7) or above post-priming (82 of 86 participants in group 1), and 92·4% (84·2-97·2) or above post-boost (73 of 79 participants in group 1). For strain NZ98/254, these proportions were 86·5% (78·0-92·6) or above post-priming (83 of 96 participants in group 2) and 88·6% (79·5-94·7) or above post-boost (70 of 79 participants in group 1). The MenC rabbit complement serum bactericidal antibody (rSBA) titre in group 1 was significantly higher than in group 2 (888·3 vs 540·4; p=0·025). There was no significant difference in geometric mean concentrations between groups 1 and 2 for diphtheria, tetanus, Hib, and pertussis post-boost. A very small number of children did not have a protective response against 44/76-SL and NZ98/254. Local and systemic reactions were similar between the two groups, apart from the 3 month timepoint when one group received an extra dose of PCV13 and recorded more systemic reactions. INTERPRETATION: These data support the recent change to the licensed European schedule for 4CMenB to add an infant 2 + 1 schedule, as used in the routine UK vaccine programme with an effectiveness of 59·1%. When compared with historical data, our data do not suggest that effectiveness would be higher with a 3 + 1 schedule, however a suboptimal boost response for bactericidal antibodies against vaccine antigen fHbp suggests a need for ongoing surveillance for vaccine breakthroughs due to fHbp-matched strains. Changing from a 2 + 1 to a 1 + 1 schedule for PCV13 for the UK is unlikely to affect protection against diphtheria, tetanus, and Hib, however an unexpected reduction in bactericidal antibodies against MenC seen with the new schedule suggests that ongoing surveillance for re-emergent MenC disease is important. FUNDING: Bill & Melinda Gates Foundation and the National Institute for Health Research.


Assuntos
Esquemas de Imunização , Imunogenicidade da Vacina/imunologia , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/imunologia , Animais , Anticorpos Antibacterianos , Humanos , Lactente , Vacinas Meningocócicas/administração & dosagem , Neisseria meningitidis/imunologia , Neisseria meningitidis Sorogrupo C , Vacinas Pneumocócicas , Coelhos , Toxoide Tetânico , Reino Unido , Vacinação , Vacinas Conjugadas/imunologia
13.
Hum Vaccin Immunother ; 16(6): 1306-1312, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32233959

RESUMO

NEISSERIA MENINGITIDIS: can lead to invasive meningococcal disease to which young children are particularly vulnerable. We assessed the immunogenicity and safety of Sanofi Pasteur's investigational quadrivalent (serogroups A, C, Y, and W) meningococcal tetanus-toxoid conjugate vaccine, MenACYW-TT, as a single dose, in healthy meningococcal vaccine-naïve toddlers versus a licensed conjugate vaccine MCV4-TT (NCT03205358). In this Phase II study conducted in Finland, 188 toddlers aged 12-24 months were randomized 1:1 to MenACYW-TT or MCV4-TT. Serum bactericidal antibody assays using human complement (hSBA) and baby rabbit complement (rSBA) measured antibodies against each serogroup before and 30 days after vaccination. Participants were monitored for immediate adverse events (AEs) and post-vaccination AEs for 30 days. All analyses were descriptive. All 188 participants completed the study. The Day 30 hSBA seroresponses (hSBA titer <8 at baseline and post-vaccination titer ≥8, or ≥8 at baseline and ≥4-fold increase post-vaccination) were comparable between participants receiving MenACYW-TT (96.7-100%), and MCV4-TT (86.0-100.0%) for each serogroup. Most unsolicited AEs were of Grade 1 or Grade 2 intensity. There were no immediate hypersensitivity reactions, and no AEs or serious AEs leading to discontinuation from the study. In this exploratory study, MenACYW-TT vaccine was well tolerated and immunogenic. If confirmed in Phase III, a single dose of the MenACYW-TT vaccine may show promise as an alternative vaccine option for toddlers receiving meningococcal vaccination for the first time.


Assuntos
Infecções Meningocócicas , Vacinas Meningocócicas , Anticorpos Antibacterianos , Feminino , Finlândia , Humanos , Lactente , Masculino , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/imunologia , Toxoide Tetânico , Vacinas Conjugadas/imunologia
14.
Open Forum Infect Dis ; 7(5): ofaa143, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32494580

RESUMO

BACKGROUND: The 4-component capsular group B meningococcal vaccine (4CMenB) was licensed as a 4-dose infant schedule but introduced into the United Kingdom as 3 doses at 2, 4, and 12 months of age. We describe the immunogenicity and reactogenicity of the 2 + 1 schedule in infants. METHODS: Infants were randomized to receive 4CMenB with routine immunizations (test group) at 2, 4, and 12 months or 4CMenB alone at 6, 8, and 13 months of age (control group). Serum bactericidal antibody (SBA) assay against a serogroup B meningococcal reference strain (44/76-SL), memory B-cell responses to factor H binding protein, Neisseria adhesion protein A, Neisseria heparin binding antigen, Porin A (PorA), and reactogenicity was measured. RESULTS: One hundred eighty-seven infants were randomized (test group: 94; control group: 93). In the test group, 4CMenB induced SBA titers above the putative protective threshold (1:4) after primary and booster doses in 97% of participants. Postbooster, the SBA GMT (72.1; 95% confidence interval [CI], 51.7-100.4) was numerically higher than the serum bactericidal antibody geometric mean titre (SBA GMT) determined post-primary vaccination (48.6; 95% CI, 37.2-63.4). After primary immunizations, memory B-cell responses did not change when compared with baseline controls, but frequencies significantly increased after booster. Higher frequency of local and systemic adverse reactions was associated with 4CMenB. CONCLUSIONS: A reduced schedule of 4CMenB was immunogenic and established immunological memory after booster.

15.
Lancet Infect Dis ; 18(10): 1088-1096, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30120069

RESUMO

BACKGROUND: Invasive meningococcal disease is an important public health problem, especially in sub-Saharan Africa. After introduction of MenAfriVac in 2010, Neisseria meningitidis serogroup A disease has been almost eliminated from the region. However, serogroups C, W, Y, and X continue to cause disease outbreaks. We assessed the NmCV-5 pentavalent meningococcal conjugate vaccine targeting A, C, Y, W, and X serogroups in a first-in-man, phase 1 study. METHODS: We did a single-centre, double-blind, randomised controlled trial at a research clinic in Baltimore (MD, USA). Participants were healthy adults aged 18-45 years with no history of meningococcal vaccination or previous meningococcal infection. We randomly assigned participants (1:1:1) by an SAS-generated random schedule to a single, 0·5 mL, intramuscular injection of aluminium-phosphate adjuvanted NmCV-5, non-adjuvanted NmCV-5, or control (the quadrivalent meningococcal conjugate vaccine Menactra). The randomisation sequence used a permuted block design with randomly chosen block sizes of three and six. The vaccines were prepared, labelled, and administered with procedures to ensure participants and study personnel remained masked to treatment. After vaccination, participants were observed in the clinic for 60 min for adverse reactions. Participants recorded daily temperature and injection site or systemic reactions at home and returned to the clinic for follow-up visits on days 7, 28, and 84 for safety assessments; blood samples were also collected on day 7 for safety laboratory assessment. A phone call contact was made 6 months after vaccination. Serum was collected before vaccination and 28 days after vaccination for immunological assessment with a rabbit complement-dependent serum bactericidal antibody (rSBA) assay. The primary objective was an intention-to-treat assessment of safety, measuring local and systemic reactogenicity over 7 days, unsolicited adverse events through 28 days, and serious adverse events over 6 months. The secondary objective for the assessment of immunogenicity, was a per-protocol analysis of rSBA before and 28 days after vaccination. This trial is registered with ClinicalTrials.gov, number NCT02810340. FINDINGS: Between Aug 17, 2016, and Feb 16, 2017, we assigned 20 participants to each vaccine. All vaccines were well-tolerated. Pain was the most common local reaction, occurring in 12 (60%), ten (50%), and seven (35%) participants in the adjuvanted NmCV-5, non-adjuvanted NmCV-5, and control groups, respectively. Headache was the most common systemic reaction, occurring in five (25%), three (15%), and three (15%), respectively. Most solicited reactogenicity adverse reactions were mild (60 [74%] of 81) and all were self-limiting. None of the differences in proportions of individuals with each solicited reaction was significant (p>0·300 for all comparisons) between the three vaccination groups. There were no serious adverse events and 19 unsolicited non-serious adverse events in 14 (23%) participants. Both adjuvanted and non-adjuvanted NmCV-5 elicited high rSBA titres against all five meningococcal serogroups. The pre-vaccination geometric mean titres (GMTs) ranged from 3·36 to 53·80 for the control, from 6·28 to 187·00 for the adjuvanted vaccine, and from 4·29 to 350·00 for the non-adjuvanted vaccine, and the post-vaccination GMT ranged from 3·14 to 3214 for the control, from 1351 to 8192 for the adjuvanted vaccine, and from 1607 to 11 191 for the non-adjuvanted vaccine. Predicted seroprotective responses (ie, an increase in rSBA titres of eight times or more) for the adjuvanted and non-adjuvanted NmCV-5 were similar to control responses for all five serogroups. INTERPRETATION: The adjuvanted and non-adjuvanted NmCV-5 vaccines were well tolerated and did not produce concerning adverse effects and resulted in immune responses that are predicted to confer protection against all five targeted serogroups of invasive meningococcal disease. Further clinical testing of NmCV-5 is ongoing, and additional clinical trials are necessary to confirm the safety and immunogenicity of NmCV-5 in target populations. FUNDING: UK Department for International Development.


Assuntos
Vacinas Meningocócicas/imunologia , Neisseria meningitidis/classificação , Adolescente , Adulto , Método Duplo-Cego , Humanos , Vacinas Meningocócicas/efeitos adversos , Pessoa de Meia-Idade , Sorogrupo , Vacinação , Vacinas Conjugadas/imunologia , Adulto Jovem
16.
Vaccine ; 36(10): 1297-1303, 2018 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-29397226

RESUMO

BACKGROUND: Capsular group X N. meningitidis (MenX) has emerged as a cause of localized disease outbreaks in sub-Saharan Africa, but the human immune response following exposure to MenX antigens is poorly described. We therefore assessed the natural immunity against MenX in individuals who were living in an area affected by a MenX outbreak during 2007 in Togo, West Africa. During 2009, 300 healthy individuals (100 aged 3-5 years, 100 aged 13-19 years and 100 aged 20-25 years) were included in the study, and serum responses were compared with sera from age-matched controls from the U.K. and Burkina Faso. METHODS: MenX serum bactericidal antibody (SBA) was measured using rabbit complement, and antibodies against MenX polysaccharide (XPS) and outer membrane vesicles (XOMVs) were quantified by ELISA. RESULTS: The proportion of Togolese individuals with an SBA titer of ≥8 against the MenX strain was 29% (95% confidence interval (CI) 18-41) among those aged 3-5 years, 34% (95% CI 9-60) among those aged 13-19 years and 32% (95% CI 24-40) among those aged 20-25 years. These were significantly higher than observed in the control populations from the U.K (range 13-16%) and Burkina Faso (range 2-6%). CONCLUSION: In Togolese individuals, the concentration of serum IgG against XPS was higher among the two older age groups as compared to the youngest age group. Antibody concentrations against MenX PS correlated significantly with SBA titers. This supports further development of a MenX PS based conjugate vaccine. Further studies are needed to verify the ability of MenX PS to induce SBA in humans.


Assuntos
Imunidade Inata , Meningite Meningocócica/epidemiologia , Meningite Meningocócica/imunologia , Neisseria meningitidis/imunologia , Adolescente , Adulto , Fatores Etários , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Criança , Pré-Escolar , Surtos de Doenças , Feminino , Humanos , Imunoglobulina G/imunologia , Masculino , Meningite Meningocócica/prevenção & controle , Vacinas Meningocócicas/imunologia , Vigilância da População , Estudos Soroepidemiológicos , Togo/epidemiologia , Adulto Jovem
17.
PLoS One ; 12(8): e0182575, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28796795

RESUMO

BACKGROUND: Serum bactericidal antibody titres that correlate with protection against invasive meningococcal disease have been characterised. However, titres that are associated with protection against acquisition of pharyngeal carriage of Neisseria meningitidis are not known. METHODS: Sera were obtained from the members of a household in seven countries of the African meningitis belt in which a pharyngeal carrier of N. meningitidis had been identified during a cross-sectional survey. Serum bactericidal antibody titres at baseline were compared between individuals in the household of the carrier who became a carrier of a meningococcus of the same genogroup during six months of subsequent follow-up and household members who did not become a carrier of a meningococcus of this genogroup during this period. RESULTS: Serum bacterial antibody titres were significantly higher in carriers of a serogroup W or Y meningococcus at the time of recruitment than in those who were not a carrier of N. meningitidis of the same genogroup. Serum bactericidal antibody titres to a strain of N. meningitis of the same genogroup as the index cases were no different in individuals who acquired carriage with a meningococcus of the same genogroup as the index case than in those who did not become a carrier during six months of follow-up. CONCLUSION: Serum bacterial antibody titres to N. meningitidis of genogroup W or Y in the range of those acquired by natural exposure to meningococci of these genogroups, or with cross-reactive bacteria, are not associated with protection against acquisition of carriage with meningococci of either of these genogroups.


Assuntos
Doenças Endêmicas , Meningite Meningocócica/microbiologia , Neisseria meningitidis Sorogrupo W-135/imunologia , Neisseria meningitidis Sorogrupo Y/imunologia , Faringe/microbiologia , Anticorpos Antibacterianos/sangue , Portador Sadio , Estudos Transversais , Feminino , Humanos , Masculino , Meningite Meningocócica/epidemiologia , Meningite Meningocócica/imunologia , Meningite Meningocócica/prevenção & controle , Fatores de Proteção , Fatores de Risco , Vacinação , Adulto Jovem
18.
Microbes Infect ; 8(8): 2098-104, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16777457

RESUMO

We investigated the carriage of serogroup W135 meningococci and its relationship with protective immunity in Niamey. Between February and May 2003, three oropharyngeal swabs and two serum samples were each taken from 287 school children. Serogroup W135 isolates were obtained from 8.9% of children. Specific IgG > or = 2 microg/ml using ELISA or serum bactericidal assay (SBA) titre > or = 8 were supposed to represent the protective immunity to a serogroup. The proportion of children with serogroup W135-specific IgG > or = 2 microg/ml increased significantly during follow-up (13.9% to 19.1%), but not the proportion of those with SBA titre > or = 8 (10.1% to 11.6%). At the end of the follow-up, we observed a significant association between carriage of serogroup W135 strains and presumed protective immunity to this serogroup, using either ELISA or SBA. Among 240 children having an initial SBA titre < 8, 20 carried serogroup W135 strains at least once. In May, 25% of carriers had an SBA titre > or = 8, vs. 2.3% of non-carriers. For ELISA, 230 children had specific IgG < 2 microg/ml in February, with 22 having at least one swab positive for serogroup W135 meningococci later. In May, 45.5% of them had specific IgG > or = 2 microg/ml vs. 5.3% among non-carriers.


Assuntos
Portador Sadio/epidemiologia , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/imunologia , Neisseria meningitidis Sorogrupo W-135/imunologia , Neisseria meningitidis Sorogrupo W-135/isolamento & purificação , Adolescente , Anticorpos Antibacterianos/sangue , Portador Sadio/microbiologia , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Infecções Meningocócicas/microbiologia , Viabilidade Microbiana , Níger/epidemiologia , Prevalência , Estudos Prospectivos , Estatística como Assunto
19.
Vaccine ; 34(34): 3931-4, 2016 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-27317452

RESUMO

Children who develop invasive Haemophilus influenzae serotype b (Hib) disease after immunisation with a highly-effective conjugate vaccine are more likely to have been infected with Hib strains possessing multiple copies of the capsulation locus. Using a recently-validated serum bactericidal antibody (SBA) assay, we tested convalescent sera from 127 Hib vaccine failure cases against clinical Hib strains expressing 1-5 copies of the capsulation locus. SBA titres correlated weakly with anti-capsular IgG antibody concentrations and there was no association between SBA geometric mean titres and number of capsulation locus copies. After infection, children with Hib vaccine failure were equally protected against Hib strains with 1-5 copies of the capsulation locus.


Assuntos
Anticorpos Antibacterianos/sangue , Infecções por Haemophilus/prevenção & controle , Vacinas Anti-Haemophilus/uso terapêutico , Cápsulas Bacterianas , Pré-Escolar , Haemophilus influenzae tipo b , Humanos , Imunoglobulina G/sangue , Lactente , Ensaios de Anticorpos Bactericidas Séricos , Falha de Tratamento , Vacinas Conjugadas/uso terapêutico
20.
Vaccine ; 34(36): 4327-34, 2016 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-27395566

RESUMO

BACKGROUND: A decline of protective antibody titers after MCC vaccine has been demonstrated in healthy children, this may be an issue of concern for risk groups. The aim of this study was to evaluate the persistence of bactericidal antibodies after MCC vaccine in sickle cell disease (SCD) patients. The type of vaccine used and booster response were also analyzed. METHODS: SCD patients (n=141) previously immunized with MCC vaccines had blood drawn 2-8 years after the last priming dose. They were distributed according to age at primary immunization into groups: <2 years and 2-13 years and evaluated by years since vaccination (2-3, 4-5 and 6-8). Serum bactericidal antibodies with baby rabbit complement (rSBA) and serogroup C-specific IgG concentrations were measured. The correlate of protection was rSBA titer ⩾8. Subjects with rSBA <8 received a booster dose and antibody levels re-evaluated after 4-6 weeks. RESULTS: For children primed under 2years of age rSBA titer ⩾8 was demonstrated in 53.3%, 21.7% and 35.0%, 2-3, 4-5, 6-8years, respectively, after vaccination, compared with 70.0%, 45.0% and 53.5%, respectively, for individuals primed at ages 2-13years. rSBA median titers and IgG median levels were higher in the older group. Six to eight years after vaccination the percentage of patients with rSBA titers ⩾8 was significantly higher in the group primed with MCC-TT (78.5%) compared with those primed with MCC-CRM197 [Menjugate® (33.3%) or Meningitec® (35.7%)] (p=0.033). After a booster, 98% achieved rSBA titer ⩾8. CONCLUSION: Immunity to meningococcal serogroup C in SCD children declines rapidly after vaccination and is dependent on the age at priming. Booster doses are needed to maintain protection in SCD patients. Persistence of antibodies seems to be longer in individuals primed with MCC-TT vaccine comparing to those immunized with MCC-CRM197.


Assuntos
Anemia Falciforme/imunologia , Anticorpos Antibacterianos/sangue , Infecções Meningocócicas/imunologia , Vacinas Meningocócicas/imunologia , Neisseria meningitidis Sorogrupo C/imunologia , Vacinas Conjugadas/imunologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Imunização Secundária , Masculino , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/prevenção & controle , Ensaios de Anticorpos Bactericidas Séricos , Fatores de Tempo
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