RESUMEN
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).
Asunto(s)
Adyuvantes Inmunológicos , Anticuerpos Antibacterianos , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular , Inmunización Secundaria , Oligodesoxirribonucleótidos , Tos Ferina , Humanos , Adolescente , Femenino , Masculino , Anticuerpos Antibacterianos/sangre , Inmunización Secundaria/métodos , Adulto , Adulto Joven , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/efectos adversos , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/efectos adversos , Niño , Oligodesoxirribonucleótidos/administración & dosificación , Oligodesoxirribonucleótidos/inmunología , Tos Ferina/prevención & control , Tos Ferina/inmunología , Anticuerpos Neutralizantes/sangre , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Vacuna contra Difteria, Tétanos y Tos Ferina/efectos adversos , Tétanos/prevención & control , Tétanos/inmunología , Voluntarios Sanos , Inmunogenicidad VacunalRESUMEN
In France, the goal of the pertussis vaccination program is to protect newborns. All infants are vaccinated under the program and then given booster shots up to the age of 25 years. Pregnant women are likewise vaccinated, with the cocooning strategy reserved for infants born to unvaccinated mothers. Real-world data shows (i) inadequate coverage among adolescents and adults under 25; (ii) improper use of the tetanus, diphtheria, and polio (Td/IPV) vaccine in children under six years, adolescents, and young adults; and (iii) underdiagnosis of pertussis in adults. Older patients or those with specific chronic medical conditions are at risk of developing severe disease. Improving the diagnosis and surveillance of pertussis in adults and seniors would be one of the first steps in the right direction. Aligning pertussis vaccination in adults with the Td/IPV program (boosters at 45, 65 years of age, and then every 10 years) would make the vaccination schedule simpler, easier to understand, and easier to implement. Large-scale awareness campaigns targeting this population would increase coverage, thereby boosting the effectiveness of the other measures.
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Vacuna contra la Tos Ferina , Vacunación , Tos Ferina , Humanos , Tos Ferina/prevención & control , Tos Ferina/epidemiología , Francia , Adulto , Vacuna contra la Tos Ferina/administración & dosificación , Vacunación/métodos , Femenino , Programas de Inmunización/métodos , Embarazo , Adolescente , Adulto Joven , Inmunización Secundaria , Esquemas de Inmunización , Anciano , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Persona de Mediana Edad , Cobertura de Vacunación/estadística & datos numéricosRESUMEN
Bordetella pertussis is a Gram-negative bacterium that is the causative agent of the respiratory disease known as pertussis. Since the switch to the acellular vaccines of DTaP and Tap, pertussis cases in the US have risen and cyclically fallen. We have observed that mRNA pertussis vaccines are immunogenic and protective in mice. Here, we further evaluated the pertussis toxoid mRNA antigen and refined the formulation based on optimal pertussis toxin neutralization in vivo. We next evaluated the mRNA pertussis vaccine in Sprague-Dawley rats using an aerosol B. pertussis challenge model paired with whole-body plethysmography to monitor coughing and respiratory function. Female Sprague-Dawley rats were primed and boosted with either commercially available vaccines (DTaP or wP-DTP), an mRNA-DTP vaccine, or mock-vaccinated. The mRNA-DTP vaccine was immunogenic in rats and induced antigen-specific IgG antibodies comparable to DTaP. Rats were then aerosol challenged with a streptomycin-resistant emerging clinical isolate D420Sm1. Bacterial burden was assessed at days 1 and 9 post-challenge, and the mRNA vaccine reduced burden equal to both DTaP and wP-DTP. Whole-body plethysmography revealed that mRNA-DTP vaccinated rats were well protected against coughing which was comparable to the non-challenged group. These data suggest that an mRNA-DTP vaccine is immunogenic in rats and provides protection against aerosolized B. pertussis challenge in Sprague-Dawley rats.
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Bordetella pertussis , Ratas Sprague-Dawley , Tos Ferina , Animales , Tos Ferina/prevención & control , Tos Ferina/inmunología , Femenino , Ratas , Bordetella pertussis/inmunología , Bordetella pertussis/genética , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Inmunoglobulina G/sangre , Vacunas de ARNm , InmunizaciónAsunto(s)
Difteria , Sistema de Registros , Tétanos , Cobertura de Vacunación , Tos Ferina , Humanos , Australia/epidemiología , Cobertura de Vacunación/estadística & datos numéricos , Anciano , Femenino , Masculino , Difteria/prevención & control , Difteria/epidemiología , Tos Ferina/prevención & control , Tos Ferina/epidemiología , Tétanos/prevención & control , Tétanos/epidemiología , Anciano de 80 o más Años , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Toxoide Tetánico/administración & dosificación , Vacuna contra la Tos Ferina/administración & dosificaciónRESUMEN
BACKGROUND: "Zero-dose" children are those who are without any routine vaccination or are lacking the first dose of the diphtheria, tetanus, and pertussis-containing vaccine. Based on global estimates from the World Health Organization/United Nations Children's Fund in 2022, Nigeria has the highest number of zero-dose children, with >2.3 million unvaccinated. METHODS: We used data from the 2021 Nigeria Multiple Indicator Cluster Survey/National Immunization Coverage Survey to identify zero-dose and underimmunized children. Geospatial modeling techniques were employed to determine the prevalence of zero-dose children and predict risk areas with underimmunized children at a high resolution (1 × 1â km). RESULTS: Zero-dose and underimmunized children are more prevalent in socially deprived groups. Univariate and multivariate bayesian analyses showed positive correlations between the prevalence of zero-dose and underimmunized children and factors such as stunting, contraceptive prevalence, and literacy. The prevalence of zero-dose and underimmunized children varies significantly by region and ethnicity, with higher rates observed in the country's northern parts. Significant heterogeneity in the distribution of undervaccinated children was observed. CONCLUSIONS: Nigeria needs to enhance its immunization system and coverage. Geospatial modeling can help deliver vaccines effectively to underserved communities. By adopting this approach, countries can ensure equitable vaccine access and contribute to global vaccination objectives.
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Cobertura de Vacunación , Humanos , Nigeria/epidemiología , Lactante , Cobertura de Vacunación/estadística & datos numéricos , Femenino , Masculino , Preescolar , Teorema de Bayes , Programas de Inmunización , Vacunación/estadística & datos numéricos , Prevalencia , Niño , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificaciónRESUMEN
To fully understand the safety of DTaP-IPV/Hib vaccination, we evaluated the differences between DTaP-IPV/Hib co-administration and separate administration of the DTaP, IPV and Hib vaccines (DTaP+IPV+Hib) based on adverse events following immunization (AEFI). All AEFI reported in Hebei Province, China, between 2020 and 2022 were included in this study. The risk difference (RD%), relative risk (RR), and Chi-square value were used to compare the differences in reported rates of AEFI between the DTaP-IPV/Hib and DTaP+IPV+Hib groups. From 2020 to 2022, 130 AEFI cases were reported in Hebei Province after DTaP-IPV/Hib vaccination, corresponding to an AEFI reported rate of 66.9/million doses, which was significantly lower than that for DTaP+IPV+Hib (9836 AEFI with a reported rate of 637.8/million doses). The overall reported rate of non-severe AEFI for DTaP+IPV+Hib vaccines was 9.5 times that of DTaP-IPV/Hib vaccination [95% confidence interval (CI): 8.0, 11.3]. Meanwhile, the reported rate of AEFI among infants aged 0-1 y was 9.8 times higher for DTaP+IPV+Hib than for DTaP-IPV/Hib (95% CI: 8.2, 11.7). DTaP+IPV+Hib vaccination also resulted in higher risks of high fever, localized redness and swelling, localized induration, and allergic rash compared with DTaP-IPV/Hib vaccination. The risk of AEFI, which were mostly mild reaction, was higher after vaccination with DTaP+IPV+Hib than after DTaP-IPV/Hib vaccination.
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Vacuna contra Difteria, Tétanos y Tos Ferina , Vacunas contra Haemophilus , Vacuna Antipolio de Virus Inactivados , Vacunas Combinadas , Humanos , Vacunas contra Haemophilus/efectos adversos , Vacunas contra Haemophilus/administración & dosificación , Vacuna Antipolio de Virus Inactivados/efectos adversos , Vacuna Antipolio de Virus Inactivados/administración & dosificación , Vacuna contra Difteria, Tétanos y Tos Ferina/efectos adversos , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Lactante , Vacunas Combinadas/efectos adversos , Vacunas Combinadas/administración & dosificación , China/epidemiología , Femenino , Masculino , Vacunación/efectos adversos , Infecciones por Haemophilus/prevención & control , Esquemas de Inmunización , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/efectos adversos , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificaciónAsunto(s)
Vacunas contra Haemophilus , Vacunas contra Hepatitis B , Padres , Vacuna Antipolio de Virus Inactivados , Humanos , China , Vacunas contra Haemophilus/economía , Vacunas contra Hepatitis B/economía , Vacunas contra Hepatitis B/administración & dosificación , Estudios Transversales , Padres/psicología , Vacuna Antipolio de Virus Inactivados/economía , Vacuna Antipolio de Virus Inactivados/administración & dosificación , Vacunas Combinadas/economía , Aceptación de la Atención de Salud/psicología , Encuestas y Cuestionarios , Vacunación/economía , Vacunación/psicología , Vacuna contra Difteria, Tétanos y Tos Ferina/economía , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , LactanteRESUMEN
BACKGROUND: In many countries, infant vaccination with acellular pertussis (aP) vaccines has replaced use of more reactogenic whole-cell pertussis (wP) vaccines. Based on immunological and epidemiological evidence, we hypothesised that substituting the first aP dose in the routine vaccination schedule with wP vaccine might protect against IgE-mediated food allergy. We aimed to compare reactogenicity, immunogenicity, and IgE-mediated responses of a mixed wP/aP primary schedule versus the standard aP-only schedule. METHODS AND FINDINGS: OPTIMUM is a Bayesian, 2-stage, double-blind, randomised trial. In stage one, infants were assigned (1:1) to either a first dose of a pentavalent wP combination vaccine (DTwP-Hib-HepB, Pentabio PT Bio Farma, Indonesia) or a hexavalent aP vaccine (DTaP-Hib-HepB-IPV, Infanrix hexa, GlaxoSmithKline, Australia) at approximately 6 weeks old. Subsequently, all infants received the hexavalent aP vaccine at 4 and 6 months old as well as an aP vaccine at 18 months old (DTaP-IPV, Infanrix-IPV, GlaxoSmithKline, Australia). Stage two is ongoing and follows the above randomisation strategy and vaccination schedule. Ahead of ascertainment of the primary clinical outcome of allergist-confirmed IgE-mediated food allergy by 12 months old, here we present the results of secondary immunogenicity, reactogenicity, tetanus toxoid IgE-mediated immune responses, and parental acceptability endpoints. Serum IgG responses to diphtheria, tetanus, and pertussis antigens were measured using a multiplex fluorescent bead-based immunoassay; total and specific IgE were measured in plasma by means of the ImmunoCAP assay (Thermo Fisher Scientific). The immunogenicity of the mixed schedule was defined as being noninferior to that of the aP-only schedule using a noninferiority margin of 2/3 on the ratio of the geometric mean concentrations (GMR) of pertussis toxin (PT)-IgG 1 month after the 6-month aP. Solicited adverse reactions were summarised by study arm and included all children who received the first dose of either wP or aP. Parental acceptance was assessed using a 5-point Likert scale. The primary analyses were based on intention-to-treat (ITT); secondary per-protocol (PP) analyses were also performed. The trial is registered with ANZCTR (ACTRN12617000065392p). Between March 7, 2018 and January 13, 2020, 150 infants were randomised (75 per arm). PT-IgG responses of the mixed schedule were noninferior to the aP-only schedule at approximately 1 month after the 6-month aP dose [GMR = 0·98, 95% credible interval (0·77 to 1·26); probability (GMR > 2/3) > 0·99; ITT analysis]. At 7 months old, the posterior median probability of quantitation for tetanus toxoid IgE was 0·22 (95% credible interval 0·12 to 0·34) in both the mixed schedule group and in the aP-only group. Despite exclusions, the results were consistent in the PP analysis. At 6 weeks old, irritability was the most common systemic solicited reaction reported in wP (65 [88%] of 74) versus aP (59 [82%] of 72) vaccinees. At the same age, severe systemic reactions were reported among 14 (19%) of 74 infants after wP and 8 (11%) of 72 infants after aP. There were 7 SAEs among 5 participants within the first 6 months of follow-up; on blinded assessment, none were deemed to be related to the study vaccines. Parental acceptance of mixed and aP-only schedules was high (71 [97%] of 73 versus 69 [96%] of 72 would agree to have the same schedule again). CONCLUSIONS: Compared to the aP-only schedule, the mixed schedule evoked noninferior PT-IgG responses, was associated with more severe reactions, but was well accepted by parents. Tetanus toxoid IgE responses did not differ across the study groups. TRIAL REGISTRATION: Trial registered at the Australian and New Zealand Clinical 207 Trial Registry (ACTRN12617000065392p).
Asunto(s)
Vacuna contra Difteria, Tétanos y Tos Ferina , Esquemas de Inmunización , Inmunoglobulina E , Humanos , Lactante , Método Doble Ciego , Inmunoglobulina E/inmunología , Inmunoglobulina E/sangre , Femenino , Masculino , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Vacuna contra Difteria, Tétanos y Tos Ferina/efectos adversos , Australia , Vacunas Combinadas/inmunología , Vacunas Combinadas/efectos adversos , Vacunas Combinadas/administración & dosificación , Vacuna contra la Tos Ferina/inmunología , Vacuna contra la Tos Ferina/efectos adversos , Vacuna contra la Tos Ferina/administración & dosificación , Hipersensibilidad a los Alimentos/inmunología , Hipersensibilidad a los Alimentos/prevención & control , Vacuna Antipolio de Virus Inactivados/inmunología , Vacuna Antipolio de Virus Inactivados/efectos adversos , Vacuna Antipolio de Virus Inactivados/administración & dosificación , Vacunas contra Haemophilus/inmunología , Vacunas contra Haemophilus/efectos adversos , Vacunas contra Haemophilus/administración & dosificación , Tos Ferina/prevención & control , Tos Ferina/inmunología , Inmunogenicidad Vacunal , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunologíaRESUMEN
BACKGROUND AND OBJECTIVES: Ensuring equitable vaccination access for immigrant communities is critical for guiding efforts to redress health disparities, but vaccine coverage data are limited. We evaluated childhood vaccination coverage by parental birth country (PBC) through the linkage of Washington State Immunization Information System data and birth records. METHODS: We conducted a retrospective cohort evaluation of children born in Washington from January 1, 2006 to November 12, 2019. We assessed up-to-date vaccination coverage status for measles, mumps, and rubella (MMR), diphtheria, tetanus, and pertussis (DTaP), and poliovirus vaccines at ages 36 months and 7 years. Children with ≥1 parent(s) born in selected non-US countries were compared with children with 2 US-born parents, using Poisson regression models to provide prevalence ratios. RESULTS: We identified 902 909 eligible children, of which 24% had ≥1 non-US-born parent(s). Vaccination coverage at 36 months by PBC ranged from 41.0% to 93.2% for ≥1 MMR doses and ≥3 poliovirus doses and 32.6% to 86.4% for ≥4 DTaP doses. Compared with children of US-born parents, the proportion of children up to date for all 3 vaccines was 3% to 16% higher among children of Filipino-, Indian-, and Mexican-born parents and 33% to 56% lower among children of Moldovan-, Russian-, and Ukrainian-born parents. Within-PBC coverage patterns were similar for all vaccines with some exceptions. Similar PBC-level differences were observed at 7 years of age. CONCLUSIONS: The linkage of public health data improved the characterization of community-level childhood immunization outcomes. The findings provide actionable information to understand community-level vaccination determinants and support interventions to enhance vaccine coverage.
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Emigrantes e Inmigrantes , Cobertura de Vacunación , Humanos , Cobertura de Vacunación/estadística & datos numéricos , Washingtón , Estudios Retrospectivos , Preescolar , Femenino , Masculino , Niño , Emigrantes e Inmigrantes/estadística & datos numéricos , Vacuna contra el Sarampión-Parotiditis-Rubéola/administración & dosificación , Padres , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificaciónRESUMEN
Globally dropout rate for the three dose of penta (DPT) vaccine was highest in the African region. This mainly occurred in the African Region including Ethiopia. Despite high national incomplete vaccination status, there is lack of study on the determinants of incomplete vaccination in south west region, Ethiopia. Therefore, this study was conducted to identify determinants of incomplete Penta vaccination among children aged 12 to 23 months in Mettu district South-West Ethiopia. A Community based case-control study was conducted from April 24, May 23, 2022 in South-west Ethiopia. Data was collected from 297 participants (99 cases and 198controls) by using simple random sampling techniques. Cases were children age from 9 to 23 months who missed at least one dose from the routine vaccine and controls were completed the entire routine vaccine schedule. Data was entered to Epi-data version 3.1 and exported to SPSS version 23 for statistical analyses. Binary and multivariable logistic regression with a 95% CI and a p-value of < 0.05 was done to declare statistical significance. A total of 95 cases and 197 controls participated in the study. Rural residence [AOR: 3.9; 95% CI; (1.6, 9.4)], wealth indexes [AOR: 3.6; 95% CI; (1.8,7.0)], mothers unimmunized tetanus toxoid [AOR: 4.3; 95% CI; (2.1, 8.6)], postponed schedule [AOR: 4.6; 95% CI; (2.4, 8.8)], un satisfied to service [AOR: 3.7; 95% CI; (1.7,7.6)] and poor perception on benefit of vaccine [AOR:2.7; 95% CI; (1.2, 6.1)] were determinants of incomplete vaccination. Rural Residence, Family wealth index of poor; Mother not received tetanus vaccination; postponed vaccination schedule client satisfaction and caretaker perception on benefit of vaccination were identified determinants of incomplete vaccination.Health information should be given for the community and child caretaker on the benefit of complete vaccination. Community should be encouraged to not post pond vaccine schedule. Pregnant women should be strengthening to receive tetanus toxoid vaccine during pregnancy.
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Vacunación , Humanos , Etiopía , Femenino , Masculino , Lactante , Vacunación/estadística & datos numéricos , Estudios de Casos y Controles , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Adulto , Esquemas de Inmunización , Cobertura de Vacunación/estadística & datos numéricosRESUMEN
Urban children are more likely to be vaccinated than rural children, but that advantage is not evenly distributed. Children living in poor urban areas face unique challenges, living far from health facilities and with lower-quality health services, which can impact their access to life-saving vaccines. Our goal was to compare the prevalence of zero-dose children in poor and non-poor urban and rural areas of low- and middle-income countries (LMICs). Zero-dose children were those who failed to receive any dose of a diphtheria-pertussis-tetanus (DPT) containing vaccine. We used data from nationally representative household surveys of 97 LMICs to investigate 201,283 children aged 12-23 months. The pooled prevalence of zero-dose children was 6.5% among the urban non-poor, 12.6% for the urban poor, and 14.7% for the rural areas. There were significant differences between these areas in 43 countries. In most of these countries, the non-poor urban children were at an advantage compared to the urban poor, who were still better off or similar to rural children. Our results emphasize the inequalities between urban and rural areas, but also within urban areas, highlighting the challenges faced by poor urban and rural children. Outreach programs and community interventions that can reach poor urban and rural communities-along with strengthening of current vaccination programs and services-are important steps to reduce inequalities and ensure that no child is left unvaccinated.
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Países en Desarrollo , Accesibilidad a los Servicios de Salud , Población Rural , Población Urbana , Humanos , Lactante , Población Rural/estadística & datos numéricos , Población Urbana/estadística & datos numéricos , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Femenino , Masculino , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Pobreza , Cobertura de Vacunación/estadística & datos numéricos , Programas de Inmunización/estadística & datos numéricos , PrevalenciaRESUMEN
Childhood vaccinations are among the most cost-effective health interventions. Yet, in India, where immunisation services are widely available free of charge, a substantial proportion of children remain unvaccinated. We revisit households 30 months after a randomised experiment of a health information intervention designed to educate mothers on the benefits of child vaccination in Uttar Pradesh, India. We find that the large short-term effects on the uptake of diphtheria-pertussis-tetanus and measles vaccination were sustained at 30 months, suggesting the intervention did not simply bring forward vaccinations. We apply causal forests and find that the intervention increased vaccination uptake, but that there was substantial variation in the magnitude of the estimated effects. We conclude that characterising those who benefited most and conversely those who benefited least provides policy-makers with insights on how the intervention worked, and how the targeting of households could be improved.
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Madres , Humanos , India , Madres/educación , Femenino , Lactante , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Educación en Salud , Preescolar , Adulto , Masculino , Vacunación/estadística & datos numéricos , Programas de Inmunización , Vacuna Antisarampión/administración & dosificaciónRESUMEN
Thailand has incorporated the whole-cell (wP) pertussis vaccine into the expanded program on immunization since 1977 and has offered the acellular pertussis (aP) vaccine as an optional vaccine for infants since 2001. We followed healthy children from a clinical trial (ClinicalTrials.gov NCT02408926) in which children were randomly assigned to receive either pentavalent (DTwP-HB-Hib) or hexavalent (DTaP-IPV-HB-Hib) vaccines for their primary series (administered at 2, 4, and 6 months) and first booster vaccination (18 months). Both groups received Tdap-IPV as a second booster at the age of 4 y. Blood samples were collected for evaluation of antibody persistence to diphtheria toxoid (DT), tetanus toxoid (TT), and Bordetella pertussis (B. pertussis) between 2 and 6 y of age annually, and for the immunogenicity study of Tdap-IPV at 1 month after the second booster. Antibody persistence to Haemophilus influenzae type b (Hib) was followed until 3 y of age. A total of 105 hexavalent-vaccinated children and 91 pentavalent-vaccinated children completed this study. Both pentavalent and hexavalent groups demonstrated increased antibody levels against DT, TT, and B. pertussis antigens following the second booster with Tdap-IPV. All children achieved a seroprotective concentration for anti-DT and anti-TT IgG at 1 month post booster. The hexavalent group possessed significantly higher anti-pertactin IgG (adjusted p = .023), whereas the pentavalent group possessed significantly higher anti-pertussis toxin IgG (adjusted p < .001) after the second booster. Despite declining levels post-second booster, a greater number of children sustained protective levels of anti-DT and anti-TT IgG compared to those after the first booster.
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Anticuerpos Antibacterianos , Bordetella pertussis , Vacuna contra Difteria, Tétanos y Tos Ferina , Vacunas contra Haemophilus , Haemophilus influenzae tipo b , Inmunización Secundaria , Vacunas Combinadas , Tos Ferina , Preescolar , Femenino , Humanos , Lactante , Masculino , Anticuerpos Antibacterianos/sangre , Bordetella pertussis/inmunología , Difteria/prevención & control , Difteria/inmunología , Toxoide Diftérico/inmunología , Toxoide Diftérico/administración & dosificación , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Infecciones por Haemophilus/prevención & control , Infecciones por Haemophilus/inmunología , Haemophilus influenzae tipo b/inmunología , Vacunas contra Haemophilus/inmunología , Vacunas contra Haemophilus/administración & dosificación , Vacuna Antipolio de Virus Inactivados/inmunología , Vacuna Antipolio de Virus Inactivados/administración & dosificación , Toxoide Tetánico/inmunología , Toxoide Tetánico/administración & dosificación , Tailandia , Vacunas Combinadas/inmunología , Vacunas Combinadas/administración & dosificación , Tos Ferina/prevención & control , Tos Ferina/inmunología , Estudios de SeguimientoRESUMEN
Since the introduction of Haemophilus Influenzae type b (Hib) conjugate vaccines, invasive Hib disease has strongly declined worldwide, yet continued control of Hib disease remains important. In Europe, currently three different hexavalent combination vaccines containing Hib conjugates are marketed. In this phase IV, single-blind, randomized, controlled, multi-country study (NCT04535037), we aimed to compare, in a 2 + 1 vaccination schedule, the immunogenicity and safety and show non-inferiority, as well as superiority, of DTPa-HBV-IPV/Hib (Ih group) versus DTaP5-HB-IPV-Hib (Va group) in terms of anti-polyribosylribitol phosphate (PRP) antibody geometric mean concentrations (GMCs) and proportion of participants reaching anti-PRP antibody concentrations greater than or equal to a threshold of 5 µg/mL. One month after the booster vaccination, the anti-PRP antibody GMC ratio (Ih group/Va group) was 0.917 (95% CI: 0.710-1.185), meeting the non-inferiority criteria. The difference in percentage of participants (Ih group - Va group) reaching GMCs ≥5 µg/mL was -6.3% (95% CI: -14.1% to 1.5%), not reaching the predefined non-inferiority threshold. Interestingly, a slightly higher post-booster antibody avidity was observed in the Ih group versus the Va group. Both vaccines were well tolerated, and no safety concerns were raised. This study illustrates the different kinetics of the anti-PRP antibody response post-primary and post-booster using the two vaccines containing different Hib conjugates and indicates a potential differential impact of concomitant vaccinations on the anti-PRP responses. The clinical implications of these differences should be further studied.
Vaccination against Haemophilus influenzae type b (Hib) is included in the majority of national immunization programs worldwide and has shown to be effective in preventing Hib disease. In Europe, different vaccines containing Hib components are marketed. We compared the immune response and safety of 2 of these (DTPa-HBV-IPV/Hib, Ih group) and DTaP5-HB-IPV-Hib, Va group) in infants and toddlers, when used in a 2 + 1 schedule, i.e. two primary vaccination doses (at 2 and 4 months of age of the infant), followed by one booster dose at the age of one year. One month after the booster vaccination, the antibody concentration ratio between both groups (Ih group/Va group) was 0.917 (95% CI: 0.7101.185) showing the DTPa-HBV-IPV/Hib vaccine was non-inferior to the DTaP5-HB-IPV-Hib vaccine; the difference in percentage of participants (Ih group Va group) with antibody concentrations above 5 µg/mL was -6.3% (95% CI: −14.1% to 1.5%), which did not meet the pre-defined criterion for non-inferiority. In the Ih group, the quality of antibodies produced was somewhat higher versus the Va group. Both vaccines were well tolerated, and no safety concerns were raised. The kinetics of the immune response are different between the 2 vaccines. Since both vaccines contain different additional components (conjugated proteins), a possible effect of concomitant (simultaneously administered) vaccines was studied. Further investigations to confirm our findings are needed.
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Anticuerpos Antibacterianos , Vacunas contra Haemophilus , Haemophilus influenzae tipo b , Esquemas de Inmunización , Polisacáridos , Vacunas Combinadas , Vacunas Conjugadas , Humanos , Vacunas contra Haemophilus/inmunología , Vacunas contra Haemophilus/efectos adversos , Vacunas contra Haemophilus/administración & dosificación , Anticuerpos Antibacterianos/sangre , Lactante , Femenino , Masculino , Método Simple Ciego , Vacunas Conjugadas/inmunología , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/efectos adversos , Haemophilus influenzae tipo b/inmunología , Vacunas Combinadas/inmunología , Vacunas Combinadas/administración & dosificación , Vacunas Combinadas/efectos adversos , Infecciones por Haemophilus/prevención & control , Infecciones por Haemophilus/inmunología , Vacunas contra Hepatitis B/inmunología , Vacunas contra Hepatitis B/administración & dosificación , Vacunas contra Hepatitis B/efectos adversos , Vacuna Antipolio de Virus Inactivados/inmunología , Vacuna Antipolio de Virus Inactivados/administración & dosificación , Vacuna Antipolio de Virus Inactivados/efectos adversos , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Vacuna contra Difteria, Tétanos y Tos Ferina/efectos adversos , Preescolar , Inmunogenicidad Vacunal , Europa (Continente)RESUMEN
BACKGROUND: Respiratory syncytial virus (RSV) fusion protein stabilized in the prefusion conformation (RSVPreF3) was under investigation as a maternal vaccine. METHODS: This phase 2, randomized, placebo-controlled, single-dose, multicenter study enrolled healthy, nonpregnant women, randomized 1:1:1:1:1 to 5 parallel groups studying RSVPreF3 (60 or 120 µg) coadministered with diphtheria, tetanus, and acellular pertussis vaccine (dTpa) or placebo, and dTpa coadministered with placebo. Safety and humoral immune responses were assessed. An extension phase also assessed a RSVPreF3 120 µg vaccination 12-18 months after first vaccination. RESULTS: The safety profile of RSVPreF3 was unaffected by dose or dTpa coadministration. Solicited and unsolicited adverse events (AEs) were evenly distributed across study groups. Injection-site pain was higher following the second vaccination versus the first vaccination. Medically attended AEs were rare (<5% overall). Both RSVPreF3 dose levels (alone and with dTpa) were immunogenic, increasing levels of RSV-A neutralizing antibody ≥8-fold and anti-RSVPreF3 IgG antibody ≥11-fold at 1 month postvaccination, which persisted at 12-18 months postvaccination; modest 2-fold increases were observed with a second RSVPreF3 vaccination. CONCLUSIONS: This study indicates RSVPreF3 coadministration with dTpa induces robust immune responses and is well tolerated, regardless of the RSVPreF3 dose level used. CLINICAL TRIALS REGISTRATION: NCT04138056.
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Anticuerpos Antivirales , Infecciones por Virus Sincitial Respiratorio , Vacunas contra Virus Sincitial Respiratorio , Humanos , Femenino , Adulto , Anticuerpos Antivirales/sangre , Infecciones por Virus Sincitial Respiratorio/prevención & control , Infecciones por Virus Sincitial Respiratorio/inmunología , Vacunas contra Virus Sincitial Respiratorio/inmunología , Vacunas contra Virus Sincitial Respiratorio/efectos adversos , Vacunas contra Virus Sincitial Respiratorio/administración & dosificación , Adulto Joven , Virus Sincitial Respiratorio Humano/inmunología , Vacuna contra Difteria, Tétanos y Tos Ferina/efectos adversos , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Inmunogenicidad Vacunal , Adolescente , Proteínas Virales de Fusión/inmunología , Proteínas Virales de Fusión/administración & dosificación , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/efectos adversos , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Vacunación/efectos adversosRESUMEN
BACKGROUND: This study investigated the immunogenicity and safety of a fully liquid, hexavalent, diphtheria (D)-tetanus (T)-whole-cell pertussis (wP)-inactivated poliovirus (IPV)-hepatitis B (HB)- Haemophilus influenzae b (PRP-T) vaccine compared to licensed DTwP-HB-PRP~T, IPV, and bivalent oral poliovirus (bOPV) vaccines following co-administration with other pediatric vaccines [pneumococcal conjugate vaccine (PCV13) and rotavirus vaccine]. METHODS: Phase III, randomized, open-label study in Thailand. Healthy infants received DTwP-IPV-HB-PRP~T at 2, 4 and 6 months of age (N = 228), or DTwP-HB-PRP~T and bOPV (2, 4 and 6 months of age) and IPV (4 months of age) (N = 231). All participants received PCV13 (2, 4 and 6 months of age) and rotavirus vaccine (2 and 4 months of age). Immunogenicity for all antigens was assessed using validated assays, and noninferiority post-third dose was evaluated for anti-D, anti-T, anti-pertussis [anti-pertussis toxin (anti-PT) and anti-fimbriae 2/3 (anti-FIM)], anti-polio 1, 2, 3, anti-HB, and anti-PRP~T. Safety was assessed using parental reports. RESULTS: Noninferiority was demonstrated for each antigen, and overall noninferiority of DTwP-IPV-HB-PRP~T versus DTwP-HB-PRP~T+bOPV+IPV was concluded. Similarity in each group was observed for the GMC ratio for antirotavirus antibodies (20.9 and 17.3, respectively) and anti-PCV13 antibodies (range: 8.46-32.6 and 7.53-33.1, respectively). Two serious adverse events were related to DTwP-IPV-HB-PRP~T (febrile convulsion and acute febrile illness) and 1 was related to DTwP-HB-PRP~T+bOPV+IPV (febrile seizure), but overall there were no safety concerns with similar rates of participants experiencing solicited (99.1% and 98.3%) and unsolicited (19.3% and 19.5%) adverse events in each group. CONCLUSIONS: This study confirmed the suitability of DTwP-IPV-HB-PRP~T primary series vaccination in combination with rotavirus and PCV13 vaccines.
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Vacuna contra Difteria, Tétanos y Tos Ferina , Vacunas contra Haemophilus , Vacunas contra Hepatitis B , Vacuna Antipolio de Virus Inactivados , Vacunas contra Rotavirus , Vacunas Combinadas , Humanos , Lactante , Anticuerpos Antibacterianos , Anticuerpos Antivirales , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Vacunas contra Haemophilus/administración & dosificación , Vacunas contra Haemophilus/inmunología , Hepatitis B , Vacunas contra Hepatitis B/administración & dosificación , Vacunas contra Hepatitis B/inmunología , Esquemas de Inmunización , Vacuna Antipolio de Virus Inactivados/administración & dosificación , Vacuna Antipolio de Virus Inactivados/inmunología , Vacunas contra Rotavirus/administración & dosificación , Vacunas contra Rotavirus/inmunología , Tailandia , Vacunas Combinadas/administración & dosificación , Vacunas Combinadas/inmunología , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/inmunología , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/inmunología , Inmunogenicidad VacunalRESUMEN
Endorsed by the World Health Assembly in 2020, the Immunization Agenda 2030 (IA2030) strives to reduce morbidity and mortality from vaccine-preventable diseases across the life course (1). This report, which updates a previous report (2), presents global, regional,* and national vaccination coverage estimates and trends as of 2020. Changes are described in vaccination coverage and the numbers of unvaccinated and undervaccinated children as measured by receipt of the first and third doses of diphtheria, tetanus, and pertussis-containing vaccine (DTP) in 2020, when the COVID-19 pandemic began, compared with 2019. Global estimates of coverage with the third dose of DTP (DTP3) and a polio vaccine (Pol3) decreased from 86% in 2019 to 83% in 2020. Similarly, coverage with the first dose of measles-containing vaccine (MCV1) dropped from 86% in 2019 to 84% in 2020. The last year that coverage estimates were at 2020 levels was 2009 for DTP3 and 2014 for both MCV1 and Pol3. Worldwide, 22.7 million children (17% of the target population) were not vaccinated with DTP3 in 2020 compared with 19.0 million (14%) in 2019. Children who did not receive the first DTP dose (DTP1) by age 12 months (zero-dose children) accounted for 95% of the increased number. Among those who did not receive DTP3 in 2020, approximately 17.1 million (75%) were zero-dose children. Global coverage decreased in 2020 compared with 2019 estimates for the completed series of Haemophilus influenzae type b (Hib), hepatitis B vaccine (HepB), human papillomavirus vaccine (HPV), and rubella-containing vaccine (RCV). Full recovery from COVID-19-associated disruptions will require targeted, context-specific strategies to identify and catch up zero-dose and undervaccinated children, introduce interventions to minimize missed vaccinations, monitor coverage, and respond to program setbacks (3).
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Salud Global , Cobertura de Vacunación/estadística & datos numéricos , Vacunas/administración & dosificación , Adolescente , Niño , Preescolar , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Objetivos , Humanos , Programas de Inmunización , Esquemas de Inmunización , Lactante , Vacuna Antisarampión/administración & dosificación , Vacunas contra Poliovirus/administración & dosificación , Organización Mundial de la SaludRESUMEN
OBJECTIVE: To analyse subnational inequality in diphtheria-tetanus-pertussis (DTP) immunization dropout in 24 African countries using administrative data on receipt of the first and third vaccine doses (DTP1 and DTP3, respectively) collected by the Joint Reporting Process of the World Health Organization and the United Nations Children's Fund. METHODS: Districts in each country were grouped into quintiles according to the proportion of children who dropped out between DTP1 and DTP3 (i.e. the dropout rate). We used six summary measures to quantify inequalities in dropout rates between districts and compared rates with national dropout rates and DTP1 and DTP3 immunization coverage. FINDINGS: The median dropout rate across countries was 2.4% in quintiles with the lowest rate and 14.6% in quintiles with the highest rate. In eight countries, the difference between the highest and lowest quintiles was 14.9 percentage points or more. In most countries, underperforming districts in the quintile with the highest rate tended to lag disproportionately behind the others. This divergence was not evident from looking only at national dropout rates. Countries with the largest inequalities in absolute subnational dropout rate tended to have lower estimated national DTP1 and DTP3 immunization coverage. CONCLUSION: There were marked inequalities in DTP immunization dropout rates between districts in most countries studied. Monitoring dropout at the subnational level could help guide immunization interventions that address inequalities in underserved areas, thereby improving overall DTP3 coverage. The quality of administrative data should be improved to ensure accurate and timely assessment of geographical inequalities in immunization.
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Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Difteria/prevención & control , Programas de Inmunización/estadística & datos numéricos , Tétanos/prevención & control , Cobertura de Vacunación/estadística & datos numéricos , Tos Ferina/prevención & control , África , Niño , Femenino , Disparidades en Atención de Salud , Humanos , Inmunización , Lactante , Masculino , Pobreza , Factores SocioeconómicosRESUMEN
In this retrospective cohort study, the response to routinely administered Haemophilus influenzae type B vaccine, pneumococcal and pertussis vaccinations in 27 children exposed to antitumor necrosis factor alpha (anti-TNFα) during pregnancy was measured. The overall vaccination response seems comparable for children exposed to anti-TNFα and healthy infants. After primary vaccination series, inadequate response was present in some patients and might be related to exposure to anti-TNFα.