RESUMO
BACKGROUND: Pregnant women, fetuses, and neonates are particularly vulnerable to vaccine-preventable diseases (VPDs). These VPDs are associated with high morbidity and mortality among expectant mothers and their fetuses and neonates. Vaccination during pregnancy can protect the expectant mother from VPDs to which she may be especially vulnerable while pregnant. In addition, the passive transfer of maternal neutralizing immunoglobulin G (IgG) and secretory immunoglobulin A (IgA) also protects the fetus against congenital infections and may further protect the neonate from infection during the first few months of life. Despite this, coverage of recommended maternal vaccines remains suboptimal globally, especially in resource-constrained settings. Determinants of vaccine acceptance and uptake are frequently understudied in low- and middle-income countries (LMICs) and among specific groups such as pregnant and postpartum women. This proposed systematic review will assess the acceptance and uptake of vaccines against tetanus, influenza, pertussis, and COVID-19 among pregnant and postpartum women in LMICs. METHODS: A Boolean search strategy employing common and medical subject heading (MeSH) terms for tetanus, influenza, pertussis, and COVID-19 vaccines, as well as vaccine acceptance, hesitancy, together with uptake, pregnancy, and postpartum, will be used to search electronic databases for relevant literature published between 2009 and 2024. Only studies conducted in LMICs that investigated determinants of acceptance, hesitancy, and uptake of tetanus, influenza, pertussis, and COVID-19 vaccines among pregnant and postpartum women will be eligible for inclusion in the review. The quality and the risk of bias of all eligible full-text articles will be assessed using the Joanna Briggs Institute's (JBI) critical appraisal tools. DISCUSSION: This protocol proposes a systematic review and meta-analysis that aims to assess the uptake of maternal vaccines and to systematically appraise and quantify determinants of the acceptance and uptake of recommended vaccines during pregnancy and postpartum in LMICs. A better understanding of these factors and how they influence maternal vaccine decision-making will enable public health practitioners as well as global and national policymakers to design more effective interventions as we look towards expanding the scope and reach of maternal immunization programs.
Assuntos
COVID-19 , Países em Desenvolvimento , Influenza Humana , Metanálise como Assunto , SARS-CoV-2 , Revisões Sistemáticas como Assunto , Tétano , Coqueluche , Humanos , Feminino , Gravidez , COVID-19/prevenção & controle , Influenza Humana/prevenção & controle , Tétano/prevenção & controle , SARS-CoV-2/imunologia , Coqueluche/prevenção & controle , Período Pós-Parto , Complicações Infecciosas na Gravidez/prevenção & controle , Vacinação/psicologia , Vacinas contra COVID-19 , Aceitação pelo Paciente de Cuidados de Saúde , Vacinas contra InfluenzaRESUMO
This phase 1 trial assessed the safety and immunogenicity of an investigational tetanus/diphtheria/acellular pertussis vaccine combined with CpG 1018 adjuvant 1500 µg (Tdap-1018 1500 µg) or 3000 µg (Tdap-1018 3000 µg) in adults and adolescents. In this randomized, active-controlled, multicenter, dose-escalation trial, healthy participants aged 10 to 22 years received 1 dose of Tdap-1018 1500 µg, Tdap-1018 3000 µg, or Boostrix. Geometric mean concentrations (GMCs) and booster response rates (BRRs) for antibodies against pertussis (pertussis toxin, filamentous hemagglutinin, pertactin), tetanus, and diphtheria antigens, and neutralizing antibodies against pertussis toxin were assessed 4 weeks after vaccination. Safety and tolerability were assessed for solicited post-injection reactions within 7 days after vaccination and unsolicited adverse events up to 12 weeks after vaccination. Of 117 enrolled participants, 80 adults (92%) and 30 adolescents (100%) completed the study. Both Tdap-1018 formulations were generally well tolerated, with no vaccine-related serious adverse events. Frequency and severity in post-injection reactions after Tdap-1018 administration were similar to Boostrix except for higher proportions of moderate pain for Tdap-1018. In adults at week 4, ratio of GMCs and BRRs for all antigens in the 3000-µg group were similar to or higher than Boostrix, with significantly higher GMC ratios for anti-pertussis toxin (2.1 [1.5-3.0]) and anti-tetanus (1.8 [1.1-2.9]) and significantly higher BRRs for anti-pertussis toxin (difference [95% CI]: 34.5% [13.4-54.6]), anti-pertactin (19.2% [4.4-38.1]), and anti-tetanus (30.0% [3.6-52.7]) antibodies. For adolescents, in the 3000-µg group, ratio of GMCs and BRRs were similar to or higher than Boostrix for all antigens. Both Tdap-1018 formulations showed acceptable safety and tolerability profiles. Tdap-1018 3000 µg induced similar or higher immune responses than Boostrix. ACTRN12620001177943 (Australian New Zealand Clinical Trials Registry; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=ACTRN12620001177943p).
Assuntos
Adjuvantes Imunológicos , Anticorpos Antibacterianos , Vacinas contra Difteria, Tétano e Coqueluche Acelular , Imunização Secundária , Oligodesoxirribonucleotídeos , Coqueluche , Humanos , Adolescente , Feminino , Masculino , Anticorpos Antibacterianos/sangue , Imunização Secundária/métodos , Adulto , Adulto Jovem , Vacinas contra Difteria, Tétano e Coqueluche Acelular/imunologia , Vacinas contra Difteria, Tétano e Coqueluche Acelular/administração & dosagem , Vacinas contra Difteria, Tétano e Coqueluche Acelular/efeitos adversos , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/efeitos adversos , Criança , Oligodesoxirribonucleotídeos/administração & dosagem , Oligodesoxirribonucleotídeos/imunologia , Coqueluche/prevenção & controle , Coqueluche/imunologia , Anticorpos Neutralizantes/sangue , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Vacina contra Difteria, Tétano e Coqueluche/efeitos adversos , Tétano/prevenção & controle , Tétano/imunologia , Voluntários Saudáveis , Imunogenicidade da VacinaRESUMO
In Malawi, tetanus toxoid vaccination (TTV) is recommended in pregnancy, but few studies have assessed the prevalence of infant seroprotection against tetanus. Anti-TT levels from 84 6-week-old infants, born in 2019-2020 to mothers living with HIV (HEU: HIV-exposed-uninfected) infants and to HIV-negative women (HUU: HIV-unexposed-uninfected) infants were determined by ELISA assay. Although 94% of the infants (HEU=94.8%, HUU=92.3%) showed protective levels (>0.1 IU/mL), the mean titers observed (0.51 IU/mL) suggest an incomplete compliance with TT vaccination. The only factor positively correlated to anti-TT IgG levels was the duration of maternal antiretroviral therapy in HEU.
Assuntos
Infecções por HIV , Toxoide Tetânico , Tétano , Humanos , Malaui/epidemiologia , Tétano/prevenção & controle , Tétano/imunologia , Infecções por HIV/imunologia , Infecções por HIV/epidemiologia , Infecções por HIV/tratamento farmacológico , Feminino , Toxoide Tetânico/imunologia , Toxoide Tetânico/administração & dosagem , Lactente , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/prevenção & controle , Masculino , Anticorpos Antibacterianos/sangue , Adulto , Vacinação , Ensaio de Imunoadsorção EnzimáticaRESUMO
INTRODUCTION AND OBJECTIVE: Vaccination is the most effective and reliable strategy for preventing the morbidity of tetanus. The aim of the study is to investigate the seroprevalence of antibodies to tetanus toxoid among healthy persons across all age groups to determine the level of vaccine-induced immunity in the population, and to identify which age group should be targeted for a booster dose. MATERIAL AND METHODS: A total of 2,842 serum samples collected between 2010 - 2019 from individuals aged from 1 month - 97 years were investigated. Anti-tetanus IgG antibody concentrations (IU/ml) were measured by an enzyme-linked immunosorbent assay. In addition, the avidity of antibodies was determined using an in-house ELISA. RESULTS: The results showed that among the 2,842 individuals, 147 (5.2%) had anti-tetanus toxoid IgG antibody levels below 0.1 IU/ml and another 1,519 (53.4%) subjects showed only basic protection (0.1-1.0 IU/ml) and needed immediate booster. High levels of anti-tetanus toxoid IgG antibodies (>1.0 IU/ml) were found more often in young adults at the age 21-40 years (55.5%, GMT=1.15). Importantly, these antibodies also had the highest avidity. With age, the percentage of high positives decreased, as well as the geometric mean and avidity of antibodies, reaching the lowest level in subjects over 70 years of age (13.3%; GMT=0.19). Characteristically, a higher percentage of high positive results was observed in men (42.6%) than in women (34.3%). CONCLUSIONS: The study showed adequate immunity levels to tetanus amongst the Polish population, especially in children, adolescents, and young adults. However, those from older age groups should receive booster doses of the vaccine.
Assuntos
Anticorpos Antibacterianos , Imunoglobulina G , Toxoide Tetânico , Tétano , Humanos , Polônia/epidemiologia , Toxoide Tetânico/imunologia , Toxoide Tetânico/administração & dosagem , Adulto , Adolescente , Criança , Estudos Soroepidemiológicos , Pré-Escolar , Adulto Jovem , Imunoglobulina G/sangue , Pessoa de Meia-Idade , Feminino , Masculino , Lactente , Idoso , Anticorpos Antibacterianos/sangue , Idoso de 80 Anos ou mais , Tétano/imunologia , Tétano/prevenção & controle , Tétano/epidemiologia , Fatores Etários , Vacinação/estatística & dados numéricosRESUMO
BACKGROUND: Nigeria has the largest number of children infected with hepatitis B virus (HBV) globally and has not yet achieved maternal and neonatal tetanus elimination. In Nigeria, maternal tetanus diphtheria (Td) vaccination is part of antenatal care and hepatitis B birth dose (HepB-BD) vaccination for newborns has been offered since 2004. We implemented interventions targeting healthcare workers (HCWs), community volunteers, and pregnant women attending antenatal care with the goal of improving timely (within 24 hours) HepB-BD vaccination among newborns and Td vaccination coverage among pregnant women. METHODS: We selected 80 public health facilities in Adamawa and Enugu states, with half intervention facilities and half control. Interventions included HCW and community volunteer trainings, engagement of pregnant women, and supportive supervision at facilities. Timely HepB-BD coverage and at least two doses of Td (Td2+) coverage were assessed at baseline before project implementation (January-June 2021) and at endline, one year after implementation (January-June 2022). We held focus group discussions at intervention facilities to discuss intervention strengths, challenges, and improvement opportunities. RESULTS: Compared to baseline, endline median vaccination coverage increased for timely HepB-BD from 2.6% to 61.8% and for Td2+ from 20.4% to 26.9% in intervention facilities (p < 0.05). In comparison, at endline in control facilities median vaccination coverage for timely HepB-BD was 7.9% (p < 0.0001) and Td2+ coverage was 22.2% (p = 0.14). Focus group discussions revealed that HCWs felt empowered to administer vaccination due to increased knowledge on hepatitis B and tetanus, pregnant women had increased knowledge that led to improved health seeking behaviors including Td vaccination, and transportation support was needed to reach those in far communities. CONCLUSION: Targeted interventions significantly increased timely HepB-BD and Td vaccination rates in intervention facilities. Continued support of these successful interventions could help Nigeria reach hepatitis B and maternal and neonatal tetanus elimination goals.
Assuntos
Vacinas contra Hepatite B , Hepatite B , Gestantes , Tétano , Cobertura Vacinal , Humanos , Feminino , Gravidez , Nigéria , Hepatite B/prevenção & controle , Vacinas contra Hepatite B/administração & dosagem , Vacinas contra Hepatite B/imunologia , Tétano/prevenção & controle , Cobertura Vacinal/estatística & dados numéricos , Recém-Nascido , Vacinação/estatística & dados numéricos , Vacinação/métodos , Adulto , Pessoal de Saúde , Cuidado Pré-Natal/métodos , Toxoide Tetânico/administração & dosagem , Toxoide Tetânico/imunologia , Programas de Imunização , Complicações Infecciosas na Gravidez/prevenção & controleAssuntos
Difteria , Sistema de Registros , Tétano , Cobertura Vacinal , Coqueluche , Humanos , Austrália/epidemiologia , Cobertura Vacinal/estatística & dados numéricos , Idoso , Feminino , Masculino , Difteria/prevenção & controle , Difteria/epidemiologia , Coqueluche/prevenção & controle , Coqueluche/epidemiologia , Tétano/prevenção & controle , Tétano/epidemiologia , Idoso de 80 Anos ou mais , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Toxoide Tetânico/administração & dosagem , Vacina contra Coqueluche/administração & dosagemRESUMO
Tetanus remains a considerable cause of mortality among undervaccinated mothers and their infants following unhygienic deliveries, especially in low-income countries. Strategies of the maternal and neonatal tetanus elimination (MNTE) initiative, which targets 59 priority countries, include strengthening antenatal immunization of pregnant women with tetanus toxoid-containing vaccines (TTCVs); conducting TTCV supplementary immunization activities among women of reproductive age in high-risk districts; optimizing access to skilled birth attendants to ensure clean deliveries and umbilical cord care practices; and identifying and investigating suspected neonatal tetanus cases. This report updates a previous report and describes progress toward MNTE during 2000-2022. By December 2022, 47 (80%) of 59 priority countries were validated to have achieved MNTE. In 2022, among the 50 countries that reported coverage with ≥2 doses of TTCV among pregnant women, 16 (32%) reported coverage of ≥80%. In 2022, among 47 validated countries, 26 (55%) reported that ≥70% of births were assisted by skilled birth attendants. Reported neonatal tetanus cases worldwide decreased 89%, from 17,935 in 2000 to 1,995 in 2021; estimated neonatal tetanus deaths decreased 84%, from 46,898 to 7,719. However, the global disruption of routine immunization caused by the COVID-19 pandemic impeded MNTE progress. Since 2020, reported neonatal tetanus cases have increased in 18 (31%) priority countries. Integration of MNTE strategies into priority countries' national postpandemic immunization recovery activities is needed to achieve and sustain global elimination.
Assuntos
Erradicação de Doenças , Saúde Global , Toxoide Tetânico , Tétano , Humanos , Tétano/prevenção & controle , Tétano/epidemiologia , Tétano/mortalidade , Feminino , Gravidez , Recém-Nascido , Saúde Global/estatística & dados numéricos , Toxoide Tetânico/administração & dosagem , Programas de Imunização , Mortalidade Infantil/tendênciasRESUMO
Probiotic microorganisms can stimulate an immune response and increase the efficiency of vaccines. For example, Bacillus toyonensis is a nonpathogenic, Gram-positive bacterium that has been used as a probiotic in animal supplementation. It induces immunomodulatory effects and increases the vaccine response in several species. This study aimed to evaluate the effect of B. toyonensis supplementation on the modulation of the immune response in horses vaccinated with recombinant Clostridium tetani toxin. Twenty horses were vaccinated twice, with an interval of 21 days between doses, and equally divided into two groups: the first group was supplemented orally for 42 days with feed containing viable spores of B. toyonensis (1 × 108) mixed with molasses (40 ml), starting 7 days before the first vaccination; the second (control) group received only feed mixed with molasses, starting 7 days before the first vaccination. Serum samples were collected to evaluate the humoral immune response using an in-house indirect enzyme-linked immunosorbent assay (ELISA), and peripheral blood mononuclear cells (PBMCs) were collected to evaluate cytokine transcription (qPCR). For the specific IgG-anti-rTENT titer, the supplemented group had ELISA values that were four times higher than those of the control group (p < 0.05). The supplemented group also showed higher ELISA values for the IgGa and IgGT sub-isotypes compared to the control group. In PBMCs stimulated with B. toyonensis, relative cytokine transcription of the supplemented group showed 15-, 8-, 7-, and 6-fold increases for IL1, TNFα, IL10 and IL4, respectively. When stimulated with a vaccine antigen, the supplemented group showed 1.6-, 1.8-, and 0.5-fold increases in IL1, TNFα, and IL4, respectively, compared to the control group. Horses supplemented with B. toyonensis had a significantly improved vaccine immune response compared to those in the control group, which suggests a promising approach for improving vaccine efficacy with probiotics.
Assuntos
Bacillus , Doenças dos Cavalos , Probióticos , Animais , Cavalos/imunologia , Bacillus/imunologia , Probióticos/administração & dosagem , Probióticos/farmacologia , Doenças dos Cavalos/prevenção & controle , Doenças dos Cavalos/imunologia , Doenças dos Cavalos/microbiologia , Tétano/prevenção & controle , Tétano/imunologia , Toxoide Tetânico/imunologia , Toxoide Tetânico/administração & dosagem , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem , Masculino , Ração Animal , Feminino , Dieta/veterinária , Citocinas/metabolismoRESUMO
Tetanus remains a potentially fatal disease with highly severe consequences worldwide. China has eliminated neonatal tetanus since 2012, but post-traumatic tetanus still represents a substantial public health burden. It is of great significance to implement active pre-exposure immunization among the high-risk group of post-traumatic tetanus in China, which can help reduce the burden of post-traumatic tetanus. Based on the World Health Organization's position paper on tetanus vaccines and relevant regulations and standards issued by China. This consensus introduces the pre-exposure immunization prevention strategies for tetanus both domestically and internationally, as well as the definition of a high-risk group of post-traumatic tetanus in China. It also provides recommendations on using active immunological preparation for tetanus, which can be used as a reference for relevant personnel engaged in disease prevention, control, and vaccination.
Assuntos
Toxoide Tetânico , Tétano , Tétano/prevenção & controle , Humanos , Toxoide Tetânico/administração & dosagem , China , Consenso , VacinaçãoRESUMO
Horses are exquisitely sensitive to tetanus neurotoxin and are exposed to the risk of infection with Clostridium tetani throughout life. The vaccine against tetanus is highly effective at preventing disease, whereas tetanus in unvaccinated populations is associated with high mortality rates. Current guidelines in New Zealand and Australia for the available vaccine contain contradictions and limitations surrounding the optimal tetanus immunisation protocols for both adult horses and foals. This review critically evaluates the scientific literature on tetanus prophylaxis in horses within the context of equine practice and available products in New Zealand and Australia. The review was conducted by a panel of industry and specialist veterinarians to obtain agreement on nine equine tetanus prophylaxis guidelines for practising veterinarians. The primary protocol for tetanus toxoid (TT) immunisation consists of a three-dose series IM for all horses ≥ 6 months of age, and a four-dose series IM is proposed if commencing vaccination in foals between 3 and 6 months of age. Tetanus prophylaxis in foals < 3 months of age relies on passive immunity strategies. Following the completion of the primary protocol, a TT booster dose IM should be administered within 5 years, and every 5 years thereafter. When followed, these protocols should provide adequate protection against tetanus in horses. Additional tetanus prophylaxis guidelines are provided for veterinarians attending a horse experiencing a known "risk event" (e.g. wound, hoof abscess, surgery, umbilical infection). When a correctly vaccinated horse experiences a risk event, pre-existing immunity provides protection against tetanus. When an unvaccinated horse or one with unknown vaccination status, or a foal born to an unvaccinated dam, experiences a risk event, TT IM and tetanus antitoxin (TAT) 1,500 IU SC should be administered simultaneously at separate sites, and the TT primary immunisation protocol should subsequently be completed for the horse's respective age. In previously immunised pregnant broodmares, a TT booster dose administered 4-8 weeks prior to parturition optimises the transfer of passive immunity against tetanus to the newborn foal via colostrum; provided that post-natal IgG concentration in serum is > 800 mg/dL (8 g/L), such foals should be passively protected against tetanus up to 6 months of age. Survivors of clinical tetanus must still receive the primary protocol for vaccination against tetanus. In summary, all horses in New Zealand and Australia should be vaccinated against tetanus with protection maintained throughout life via TT booster doses, facilitated by accurate medical record keeping and client education.
Assuntos
Doenças dos Cavalos , Toxoide Tetânico , Tétano , Cavalos , Animais , Tétano/prevenção & controle , Tétano/veterinária , Doenças dos Cavalos/prevenção & controle , Nova Zelândia , Toxoide Tetânico/administração & dosagem , Austrália , Vacinação/veterinária , Guias de Prática Clínica como AssuntoRESUMO
Tetanus toxin (TeNT) is one of the most toxic proteins. Neutralizing antibodies against TeNT are effective in prevention and treatment. In this study, 14 anti-tetanus nanobodies were obtained from a phage display nanobody library by immunizing a camel with the C-terminal receptor-binding domain of TeNT (TeNT-Hc) as the antigen. After fusion with the human Fc fragment, 11 chimeric heavy-chain antibodies demonstrated nanomolar binding toward TeNT-Hc. The results of toxin neutralization experiments showed that T83-7, T83-8, and T83-13 completely protected mice against 20 × the median lethal dose (LD50) at a low concentration. The neutralizing potency of T83-7, T83-8, and T83-13 against TeNT is 0.4 IU/mg, 0.4 IU/mg and 0.2 IU/mg, respectively. In the prophylactic setting, we found that 5 mg/kg of T83-13 provided the mice with full protection from tetanus, even when they were injected 14 days before exposure to 20 × LD50 TeNT. T83-7 and T83-8 were less effective, being fully protective only when challenged 7 or 10 days before exposure, respectively. In the therapeutic setting, 12 h after exposure to TeNT, 1 ~ 5 mg/kg of T83-7, and T83-8 could provide complete protection for mice against 5 × LD50 TeNT, while 1 mg/kg T83-13 could provide complete protection 24 h after exposure to 5 × LD50 TeNT. Our results suggested that these antibodies represent prophylactic and therapeutic activities against TeNT in a mouse model. The T83-7, T83-8, and T83-13 could form the basis for the subsequent development of drugs to treat TeNT toxicity.
Assuntos
Anticorpos Neutralizantes , Cadeias Pesadas de Imunoglobulinas , Anticorpos de Domínio Único , Toxina Tetânica , Tétano , Animais , Toxina Tetânica/imunologia , Tétano/prevenção & controle , Tétano/imunologia , Anticorpos Neutralizantes/imunologia , Camundongos , Anticorpos de Domínio Único/imunologia , Cadeias Pesadas de Imunoglobulinas/imunologia , Feminino , Camelus/imunologia , Humanos , Anticorpos Antibacterianos/imunologia , Camundongos Endogâmicos BALB CRESUMO
The conventional inactivated tetanus toxin plays an instrumental role in preventing tetanus. Nevertheless, the challenges associated with its production process, the potential for adverse reactions, and reduced effectiveness in vulnerable populations such as neonates and the elderly rise the need for a novel tetanus toxin vaccine. Recombinant subunit vaccine offer a viable solution, and the tetanus toxin fragment C (TTFC) is emerging as a promising candidate. In this study, through spontaneous isopeptide bond formation we conjugated the recombinant TTFC to self-assembled mi3 nanoparticle, which derived from an optimized KDPG aldolase, and generated the TTFC-mi3 protein nanoparticle vaccine. We found that TTFC-mi3 is stable, uniform spherical nanoparticles. Comparing with the free TTFC alone, TTFC-mi3 enhances the uptake and subsequent activation of dendric cells (DCs). In addition, a single dose of adjuvant-free TTFC-mi3 elicited a more rapid and potent protective immunity in mice. Moreover, TTFC-mi3 is of favorable safety in vitro and in vivo. Our findings indicate that TTFC-mi3 is a rapid-response, non-aluminum-adjuvanted vaccine against tetanus.
Assuntos
Nanovacinas , Toxina Tetânica , Toxoide Tetânico , Tétano , Animais , Feminino , Camundongos , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanovacinas/administração & dosagem , Nanovacinas/imunologia , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/administração & dosagem , Tétano/prevenção & controle , Tétano/imunologia , Toxina Tetânica/imunologia , Toxina Tetânica/genética , Toxoide Tetânico/imunologia , Toxoide Tetânico/administração & dosagem , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagemRESUMO
Tetanus disease, caused by C. tetani, starts with wounds or mucous layer contact. Prevented by vaccination, the lack of booster shots throughout life requires prophylactic treatment in case of accidents. The incidence of tetanus is high in underdeveloped countries, requiring the administration of antitetanus antibodies, usually derived from immunized horses or humans. Heterologous sera represent risks such as serum sickness. Human sera can carry unknown viruses. In the search for human monoclonal antibodies (mAbs) against TeNT (Tetanus Neurotoxin), we previously identified a panel of mAbs derived from B-cell sorting, selecting two nonrelated ones that binded to the C-terminal domain of TeNT (HCR/T), inhibiting its interaction with the cellular receptor ganglioside GT1b. Here, we present the results of cellular assays and molecular docking tools. TeNT internalization in neurons is prevented by more than 50% in neonatal rat spinal cord cells, determined by quantitative analysis of immunofluorescence punctate staining of Alexa Fluor 647 conjugated to TeNT. We also confirmed the mediator role of the Synaptic Vesicle Glycoprotein II (SV2) in TeNT endocytosis. The molecular docking assays to predict potential TeNT epitopes showed the binding of both antibodies to the HCR/T domain. A higher incidence was found between N1153 and W1297 when evaluating candidate residues for conformational epitope.
Assuntos
Anticorpos Monoclonais , Endocitose , Simulação de Acoplamento Molecular , Neurônios , Toxina Tetânica , Animais , Ratos , Neurônios/metabolismo , Humanos , Anticorpos Monoclonais/imunologia , Toxina Tetânica/imunologia , Toxina Tetânica/metabolismo , Tétano/prevenção & controle , Tétano/imunologia , Epitopos/imunologia , Gangliosídeos/imunologia , Gangliosídeos/metabolismo , Células Cultivadas , Simulação por Computador , MetaloendopeptidasesRESUMO
Tetanus is a preventable, yet often fatal, disease affecting many species, including beef cattle. Vaccination for tetanus is recommended for calves at high risk of disease, but typical beef cattle management practices often make adherence to vaccine manufacturers' guidance for a second (booster) dose of vaccine difficult. This study examined the antibody response following a single dose of tetanus toxoid, as well as following booster vaccination at various intervals. Anti-tetanus IgG antibodies were detectable 25 days (D25) after a single dose, and rose following booster at either D25 D109 after initial vaccination. Antibody levels then declined numerically from D109 to D179 for calves boostered at D25 but rose on D179 for those receiving a second dose on D109. The relatively rapid response in IgG production, even in the absence of a booster vaccine, may suggest value in vaccinating calves for tetanus at time of greatest risk, even if a booster cannot be administered. The study also provides support for priming of the immune response lasting at least until D109 after primary immunization.
Assuntos
Anticorpos Antibacterianos , Doenças dos Bovinos , Imunização Secundária , Toxoide Tetânico , Tétano , Vacinação , Animais , Bovinos , Toxoide Tetânico/imunologia , Toxoide Tetânico/administração & dosagem , Doenças dos Bovinos/prevenção & controle , Doenças dos Bovinos/imunologia , Anticorpos Antibacterianos/sangue , Tétano/prevenção & controle , Tétano/veterinária , Tétano/imunologia , Imunização Secundária/veterinária , Vacinação/veterinária , Imunoglobulina G/sangue , MasculinoRESUMO
BACKGROUND: In low- and middle-income countries where vaccination rates are low, tetanus is still an important threat to public health. Although maternal and neonatal tetanus remains a major global health concern, its magnitude and determinates are not well studied. Therefore, this study aimed to assess the number of tetanus toxoid injections and associated factors among pregnant women in low- and middle-income countries. METHODS: Data from the most recent Demographic and Health Surveys, which covered 60 low- and middle-income countries from 2010 to 2022, was used for secondary data analysis. The study included a total of 118,704 pregnant women. A statistical software package, STATA 14, was used to analyze the data. A negative binomial regression of a cross-sectional study was carried out. Factors associated with the number of tetanus vaccinations were declared significant at a p-value of < 0.05. The incidence rate ratio and confidence interval were used to interpret the results. A model with the smallest Akaike Information Criterion and Bayesian Information Criterion values and the highest log likelihood was considered the best-fit model for this study. RESULTS: In low- and middle-income countries, 26.0% of pregnant women took at least two doses of the tetanus toxoid vaccine. Factors such as maternal education, primary (IRR = 1.22, 95% CI: 1.17, 1.26), secondary (IRR = 1.19, 95% CI: 1.15, 1.23), higher (IRR = 1.16, 95% CI: 1.12, 1.20), employment (IRR = 1.11, 95% CI: 1.09, 1.13), 1-3 ANC visits (IRR = 2.49, 95% CI: 2.41, 2.57), ≥4 visits (IRR = 2.94, 95% CI: 2.84, 3.03), wealth index (IRR = 1.06; 95% CI: 11.04, 1.08), ≥birth order (IRR = 1.04, 95% CI: 1.02, 1.27), distance to health facility (IRR = 1.02, 95% CI: 1.00, 1.03), and health insurance coverage (IRR = 1.08; 95% CI: 1.06, 1.10) had a significant association with the number of tetanus vaccinations among pregnant women. CONCLUSIONS AND RECOMMENDATIONS: This study concludes that the number of tetanus toxoid vaccinations among pregnant women in low- and middle-income countries is low. In the negative binomial model, the frequency of tetanus vaccinations has a significant association with maternal employment, educational status, wealth index, antenatal care visits, birth order, distance from a health facility, and health insurance. Therefore, the ministries of health in low and middle-income countries should give attention to those women who had no antenatal care visits and women from poor wealth quantiles while designing policies and strategies.
Assuntos
Países em Desenvolvimento , Gestantes , Toxoide Tetânico , Tétano , Vacinação , Humanos , Feminino , Toxoide Tetânico/administração & dosagem , Gravidez , Estudos Transversais , Adulto , Tétano/prevenção & controle , Adulto Jovem , Vacinação/estatística & dados numéricos , Países em Desenvolvimento/estatística & dados numéricos , Adolescente , Distribuição de Poisson , Cobertura Vacinal/estatística & dados numéricosRESUMO
BACKGROUND: Tetanus is a non-communicable disease, preventable with vaccination. Despite the implemented vaccination strategy, a certain number of tetanus cases per year continue to occur. The aim of the study was to evaluate the seroprevalence of anti-tetanus antibodies in the Italian population by age, sex and geographical area. METHODS: To determine the level of tetanus-specific antibodies, an immunoenzymatic assay was used. RESULTS: A total of 3,821 serum samples were collected in the years 2019-20 from healthy subjects aged 6-90 years residing in 13 Italian regions. Overall, 85 % of the tested subjects resulted positive. The rate of subjects protected against tetanus showed a gradual decrease from the younger age groups to the older ones (6-12 years: 93.6 %, 13-24 years: 91.8 %, 25-39 years: 91.0 %, 40-64 years: 78.2 %, ≥ 65 years: 45.3 %); this is particularly evident in the Southern regions and Islands. Moreover, the prevalence of subjects with low protection (<0.1 IU/ml) was significantly higher in the ≥ 65 age group (10.3 %). Males and females' prevalence showed a significant difference only in the oldest age group (M: 60.8 %, F: 30.4 %). In general, a higher prevalence was observed for Northern (90.8 %) and Central regions (87.3 %) than Southern regions and Islands (80.0 %). CONCLUSION: These data, compared with epidemiological ones which showed a high number of cases in the elderly, confirmed that the population with lower protection has a greater risk of contracting the disease, demonstrating the need for adequate immunization through both primary vaccination and boosters for all ages and both sexes, in order to provide lifelong protection.
Assuntos
Anticorpos Antibacterianos , Toxoide Tetânico , Tétano , Humanos , Pessoa de Meia-Idade , Feminino , Itália/epidemiologia , Masculino , Adulto , Adolescente , Idoso , Tétano/prevenção & controle , Tétano/imunologia , Tétano/epidemiologia , Criança , Adulto Jovem , Estudos Soroepidemiológicos , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , Toxoide Tetânico/imunologia , Toxoide Tetânico/administração & dosagem , Vacinação/estatística & dados numéricos , PrevalênciaRESUMO
OBJECTIVE: This study investigated the immunogenicity and safety of a pentavalent vaccine Gobik (DPT-IPV-Haemophilus influenzae type b [Hib]) in healthy Japanese infants aged ≥ 2 and < 43 months using a concomitant vaccination with ActHIB® (Hib) and Tetrabik (DPT-IPV) as a comparator. METHODS: This study was conducted as a phase 3, multicenter, active controlled, assessor-blinded, randomized, parallel-group study. Participants received a total of 4 subcutaneous doses (3 primary immunization doses and a booster dose) of either the experimental drug (DPT-IPV-Hib) or the active comparator (Hib + DPT-IPV). The primary endpoints were the anti-PRP antibody prevalence rate with ≥ 1 µg/mL, and the antibody prevalence rates against pertussis, diphtheria toxin, tetanus toxin, and attenuated poliovirus after the primary immunization. RESULTS: In 267 randomized participants (133 in the DPT-IPV-Hib group and 134 in the Hib + DPT-IPV group), the antibody prevalence rates after the primary immunization in both groups were 100.0 % and 88.7 % for anti-PRP antibody with ≥ 1 µg/mL, 99.2 % and 98.5 % against diphtheria toxin, and 100.0 % and 99.2 % against tetanus toxin, respectively. The antibody prevalence rates against pertussis and attenuated poliovirus were 100.0 % in both groups. The non-inferiority of the DPT-IPV-Hib group to the Hib + DPT-IPV group was verified for all measured antibodies. In both groups, all the GMTs of antibodies after the primary immunization were higher than those before the first dose, and those after the booster dose were higher than those after the primary immunization. No safety issues were identified. CONCLUSION: A single-agent Gobik, the first DPT-IPV-Hib pentavalent vaccine approved in Japan, was confirmed to simultaneously provide primary and booster immunizations against Hib infection, pertussis, diphtheria, tetanus, and poliomyelitis and to have a preventive effect and safety comparable to concomitant vaccination with Hib (ActHIB®) and DPT-IPV quadrivalent vaccine (Tetrabik).
Assuntos
Difteria , Vacinas Anti-Haemophilus , Haemophilus influenzae tipo b , Poliomielite , Tétano , Coqueluche , Lactente , Humanos , Japão , Tétano/prevenção & controle , Difteria/prevenção & controle , Coqueluche/prevenção & controle , Toxina Tetânica , Toxina Diftérica , Vacina Antipólio de Vírus Inativado , Esquemas de Imunização , Anticorpos Antibacterianos , Vacina contra Difteria, Tétano e Coqueluche , Vacinas Combinadas , Poliomielite/prevenção & controle , Vacinas ConjugadasRESUMO
Diagnosis of diseases with low facilities, speed, accuracy and sensitivity is an important matter in treatment. Bioprobes based on iron oxide nanoparticles are a good candidate for early detection of deadly and infectious diseases such as tetanus due to their high reactivity, biocompatibility, low production cost and sample separation under a magnetic field. In this study, silane groups were coated on surface of iron oxide nanoparticles using tetraethoxysilane (TEOS) hydrolysis. Also, NH2groups were generated on the surface of silanized nanoparticles using 3-aminopropyl triethoxy silane (APTES). Antibody was immobilized on the surface of silanized nanoparticles using TCT trichlorothriazine as activator. Silanization and stabilized antibody were investigated by using of FT-IR, EDX, VSM, SRB technique. UV/vis spectroscopy, fluorescence, agglutination test and ELISA were used for biosensor performance and specificity. The results of FT-IR spectroscopy showed that Si-O-Si and Si-O-Fe bonds and TCT chlorine and amine groups of tetanus anti-toxoid antibodies were formed on the surface of iron oxide nanoparticles. The presence of Si, N and C elements in EDX analysis confirms the silanization of iron oxide nanoparticles. VSM results showed that the amount of magnetic nanoparticles after conjugation is sufficient for biological applications. Antibody stabilization on nanoparticles increased the adsorption intensity in the uv/vis spectrometer. The fluorescence intensity of nano bioprobe increased in the presence of 10 ng ml-1. Nanobio probes were observed as agglomerates in the presence of tetanus toxoid antigen. The presence of tetanus antigen caused the formation of antigen-nanobioprobe antigen complex. Identification of this complex by HRP-bound antibody confirmed the specificity of nanobioprobe. Tetanus magnetic nanobioprobe with a diagnostic limit of 10 ng ml-1of tetanus antigen in a short time can be a good tool in LOC devices and microfluidic chips.
Assuntos
Técnicas Biossensoriais , Propilaminas , Silanos , Toxoide Tetânico , Toxoide Tetânico/química , Toxoide Tetânico/imunologia , Silanos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Técnicas Biossensoriais/métodos , Propilaminas/química , Humanos , Ensaio de Imunoadsorção Enzimática , Nanopartículas Magnéticas de Óxido de Ferro/química , Tétano/diagnóstico , Tétano/prevenção & controle , Nanopartículas de Magnetita/química , Anticorpos Imobilizados/química , Anticorpos Imobilizados/imunologia , Limite de Detecção , Ferro/química , Testes de Aglutinação/métodosRESUMO
Pertussis (whooping cough) is a reemergent, highly contagious respiratory infection of public health concern. Infants prior to initiation of their primary vaccination series are the most vulnerable to severe infection, and even death. Vaccination during pregnancy is an efficacious means of reducing infection in infants. This approach relies on boosting maternal immunity and passive transfer of antibodies to the infant via placenta and breast milk. Similarly, maternal vaccination post-partum can enhance maternal-infant immunity. To support the analysis of pertussis immunity in the context of maternal-infant immunization, we developed a high throughput multiplex assay for simultaneous quantification of serum IgG antibodies against pertussis vaccine antigens: pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae (FIM2/3), and against tetanus (TT) and diphtheria toxoids (DT), using the Meso Scale Discovery (MSD) platform. The assay was qualified, and specificity, sensitivity, accuracy, precision, linearity, and robustness were demonstrated. The assay was subsequently adapted for quantification of IgG and IgA in breast milk. Applied to a serological survey of pregnant women living in the United States and sub-Saharan Africa, this method revealed differences in magnitude and breadth of antibody profile, consistent with history of vaccination. A longitudinal analysis of Tdap responses in women vaccinated post-partum demonstrated a rapid increase in serum IgG that remained elevated for up to 24 months. Likewise, high levels of vaccine-specific IgA and IgG antibodies were present in breast milk, although they exhibited faster decay. This multiplex MSD assay is a reliable and practical tool for quantification of pertussis, tetanus, and diphtheria antibodies in serum and breast milk in serosurveys or vaccine studies. IMPORTANCE: Pertussis (whooping cough) has reemerged in recent years. Vaccination during pregnancy is an effective approach to prevent illness during the first months of life. We developed a multiplex assay for quantification of pertussis, tetanus, and diphtheria serum antibodies using the Meso Scale Discovery (MSD) platform; the method was qualified, and specificity, precision, accuracy, linearity, and limits of quantification were defined. It was also adapted for quantification of antibodies in breast milk. We successfully determined serostatus in women from different regions and with different vaccination histories, as well as responses to Tdap in blood and breast milk post-partum. This is the first description of a multiplex assay for the quantification of pertussis, tetanus, and diphtheria antibodies in breast milk.