RESUMEN
Despite high pediatric vaccination coverage rates (VCRs), pertussis incidence has increased worldwide, including in several countries in Latin America in the last two decades. Given the few vaccine effectiveness (VE) studies in Latin American countries, this retrospective, observational, cohort study estimated the effectiveness of hexavalent acellular (aP) primary and booster vaccination (wP) against pertussis in infants (6.5-18.5 months) and children (18.5-48.5 and 48.5-72.5 months) in Panama. Age-specific incidence rates (IRs) were calculated for the vaccine's pre-initiation (2001-2013), initiation (2014), and post-initiation (2015-2019) periods. VCRs and trends were determined, and VE was analyzed using a case coverage or screening method to compare proportions of vaccinated cases and vaccinated individuals in the population. Between 2001-2019, 868 confirmed pertussis cases were reported in Panama; 712 (82.0%; 54.8 cases/year) during the pre-initiation period, 19 (2.2%; 19 cases/year) during the initiation period, and 137 (15.8%; 27.4 cases/year) during the post-initiation period. Panama underwent cyclical increases in IRs, which varied between age groups. VCRs increased for primary and booster doses. Between 2015 and 2019, third-dose yearly vaccine coverage increased, on average, 3.3%. Specifically, during the post-initiation period, 109/137 (79.6%) of cases were unvaccinated. Relative VE was estimated at 96.2% [95% CI: 86.5%, 98.9%] with three doses; 100% with 4 and 5 booster doses. Absolute VE was estimated at 99.3% with three doses only. These results show that vaccination played an important role in maintaining a low number of pertussis cases in Panama, affirming the need for sustained investment and commitment to vaccination programs.
Asunto(s)
Esquemas de Inmunización , Inmunización Secundaria , Cobertura de Vacunación , Tos Ferina , Humanos , Panamá , Lactante , Tos Ferina/prevención & control , Tos Ferina/epidemiología , Estudios Retrospectivos , Preescolar , Masculino , Niño , Femenino , Cobertura de Vacunación/estadística & datos numéricos , Incidencia , Vacuna contra la Tos Ferina/administración & dosificación , Vacuna contra la Tos Ferina/inmunología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Vacunación/estadística & datos numéricos , Vacunación/métodosRESUMEN
A panel of 24 international experts met in July 2022 to discuss challenges associated with pertussis detection, monitoring, and vaccination in adults; conclusions from this meeting are presented. There has been a shift in the epidemiology of pertussis toward older children and adults. This shift has been attributed to the waning of infection- or vaccine-induced immunity, newer detection techniques causing detection bias, and possibly the replacement of whole-cell pertussis with acellular vaccines in high-income countries, which may lead to immunity waning more quickly. The burden of adult pertussis is still likely under-ascertained due to widespread under-recognition by healthcare professionals (HCPs), under-diagnosis, and under-reporting in this age group. Non-standardized testing guidance and varied case definitions have contributed to under-reporting. Key barriers to HCP engagement with the tetanus, diphtheria, and pertussis (Tdap) vaccine include low awareness, lack of time/funding, and lack of motivation due to low prioritization of Tdap.
Asunto(s)
Vacunación , Tos Ferina , Humanos , Tos Ferina/prevención & control , Tos Ferina/epidemiología , Tos Ferina/diagnóstico , Adulto , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Vacuna contra la Tos Ferina/inmunología , Vacuna contra la Tos Ferina/administración & dosificación , Administración en Salud Pública/métodos , Salud PúblicaRESUMEN
Importance: Maternal tetanus, diphtheria, and acellular pertussis (Tdap) vaccination protects newborns against severe pertussis. Data on transplacental antibody transfer on Tdap vaccination before 24 weeks' gestation remain scarce and are particularly relevant for preterm infants to increase the time interval for maternal antibody transfer. Objective: To assess noninferiority of anti-pertussis toxin (anti-PT) immunoglobulin G (IgG) antibody levels at age 2 months in early- to late-term infants following Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation compared with 30 0/7 and 33 0/7 weeks' gestation and compared with preterm infants. Design, Setting, and Participants: This prospective, multicenter cohort study included pregnant women aged 18 years or older in birthing centers and hospitals in the Netherlands between August 2019 and November 2021 who received Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation. Women with imminent premature birth were recruited if they had received maternal Tdap vaccination between 20 and 24 weeks' gestation. Blood samples were collected from mothers at delivery, from the umbilical cord, and from infants at age 2 months. Data from infants' blood samples at age 2 months were compared with a reference cohort (recruited between January 2014 and February 2016) of early- to late-term infants of the same age whose mothers had received Tdap vaccination between 30 0/7 and 33 0/7 weeks' gestation. Exposure: Maternal Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation or 30 0/7 and 33 0/7 weeks' gestation. Main Outcomes and Measures: The primary outcome was the geometric mean concentration (GMC) of anti-PT IgG antibodies in early- to late-term infants (≥37 0/7 weeks' gestation) at age 2 months, comparing maternal Tdap vaccination between 20 0/7 and 24 0/7 weeks' vs 30 0/7 and 33 0/7 weeks' gestation (reference cohort). Anti-PT GMC in 2-month-old infants born preterm (<35 0/7 weeks' gestation) compared with early- to late-term infants after maternal Tdap vaccination between 20 and 24 weeks' gestation was a secondary outcome. Results: In total, 221 women who delivered 239 offspring were enrolled in the study; 66 early- to late-term infants (median gestational age [GA], 40.6 weeks [IQR, 39.8-41.0 weeks]; 38 [57.6%] male) and 73 preterm infants (median GA, 32.1 weeks [IQR, 29.5-33.0 weeks]; 42 [54.5%] female) had blood samples collected at 2 months of age. Anti-PT GMC was 14.7 IU/mL (95% CI, 10.6-20.4 IU/mL) in early- to late-term infants following maternal Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation compared with 27.3 IU/mL (95% CI, 20.1-37.1 IU/mL) in 55 infants in the reference group (median GA, 40.3 [IQR, 39.1-41.0]; 33 [60.0%] female). The mean anti-PT GMC in preterm infants in the study group was 11.2 IU/mL (95% CI, 8.1-15.3 IU/mL) (P = .23 compared with early- to late-term infants). Conclusions and Relevance: In this cohort study, 2-month-old preterm and early- to late-term infants showed significantly lower anti-PT antibody levels following maternal Tdap vaccination between 20 0/7 and 24 0/7 weeks' gestation compared with 30 0/7 and 33 0/7 weeks' gestation; preterm and early- to late-term infants had similar anti-PT antibody levels, but both groups showed significantly lower antibody levels compared with the reference group. Epidemiological research should investigate whether maternal Tdap vaccination before 24 weeks' gestation provides sufficient protection against clinical pertussis, particularly in preterm infants, as long as no correlate of protection is available.
Asunto(s)
Vacunas contra Difteria, Tétanos y Tos Ferina Acelular , Inmunoglobulina G , Recien Nacido Prematuro , Tos Ferina , Humanos , Femenino , Embarazo , Recien Nacido Prematuro/inmunología , Adulto , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Estudios Prospectivos , Recién Nacido , Tos Ferina/prevención & control , Tos Ferina/inmunología , Países Bajos , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Lactante , Edad Gestacional , Masculino , Inmunidad Materno-Adquirida/inmunología , VacunaciónRESUMEN
Influenza, COVID-19, tetanus, pertussis and hepatitis B pose increased risk for pregnant women and infants and could be mitigated by maternal immunization. In India Tetanus-diphtheria (Td) and COVID-19 vaccines are recommended during pregnancy, while influenza and tetanus-acellular pertussis-diphtheria (Tdap) vaccines are not. We conducted a multicenter study from November 2021 to June 2022 among pregnant women (n = 172) attending antenatal clinics in three public hospitals in West Bengal, to understand the factors that influence women's decisions to get vaccinated during pregnancy. Questions assessed vaccination coverage, knowledge, intention and willingness to pay for influenza vaccine, and factors influencing decisions to get Td, influenza, and COVID-19 vaccines. 152/172 (88.4%) women were vaccinated with Td, 159/172 (93%) with COVID-19, 1/172 (0.6%) with influenza, and none with Tdap. 10/168 (6%) had received hepatitis B vaccine (HBV). Community health workers advice was crucial for Td uptake and, the belief of protection from COVID for COVID-19 vaccines. Most women were unaware about Tdap (96%), influenza (75%), and influenza severity during pregnancy and infancy (85%). None were advised for influenza vaccination by healthcare providers (HCP), albeit, 93% expressed willingness to take, and pay INR 100-300 (95% CI: ≤100 to 300-500) [$ 1.3-4.0 (95% CI: ≤1.3, 4-6.7)] for it. Vaccination on flexible dates and time, HCP's recommendation, proximity to vaccination center, and husband's support were most important for their vaccination decisions. Women were generally vaccine acceptors and had high uptake of vaccines included in the Universal Immunization Program (UIP). Inclusion of influenza, Tdap, and HBV into UIP may improve maternal vaccine uptake.
Vaccinations during pregnancy protect mothers and babies from lethal infections from tetanus, influenza, COVID-19, pertussis, and hepatitis B. In India all pregnant women get tetanus (Td) vaccines, and during the pandemic, pregnant women got COVID-19 vaccines as part of the government program. We conducted a study among pregnant women attending three public hospitals in West Bengal, India, during the COVID-19 pandemic to understand the factors that influence women's decisions to get vaccinated during pregnancy. We found that most pregnant women had gotten Td (88.4%) and COVID-19 (93%) vaccines; however, the uptake was low for influenza (0.6%), pertussis (0%), and hepatitis B vaccines (6%) which are all not available in government programs. Though the majority (92%) of women had not heard about influenza vaccines, once they learnt about them, 93% said they would get vaccinated and even pay for it. Vaccination at flexible times and their doctor's advice were important in their decisions to get vaccinated. Our research builds the case to include influenza, pertussis, and hepatitis B vaccines in programs for pregnant women.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Vacunación , Humanos , Femenino , Embarazo , India/epidemiología , COVID-19/prevención & control , COVID-19/epidemiología , Adulto , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/inmunología , Vacunación/psicología , Vacunación/estadística & datos numéricos , Conocimientos, Actitudes y Práctica en Salud , Adulto Joven , Mujeres Embarazadas/psicología , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/inmunología , Aceptación de la Atención de Salud/estadística & datos numéricos , Aceptación de la Atención de Salud/psicología , Cobertura de Vacunación/estadística & datos numéricos , SARS-CoV-2/inmunología , Complicaciones Infecciosas del Embarazo/prevención & control , Vacilación a la Vacunación/estadística & datos numéricos , Vacilación a la Vacunación/psicología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunologíaRESUMEN
BACKGROUND: Maternal pertussis vaccination with Tdap vaccine is recommended to protect newborns from severe postnatal infection. HIV-exposed uninfected (HEU) infants have a higher incidence of pertussis infection and may particularly benefit from maternal immunization. The impact of HIV infection on the quality of IgG and memory B cell (MBC) responses to Tdap vaccination in pregnant women (PW) living with HIV (PWH) is unknown. METHODS: In this observational study, humoral immune responses to Tdap vaccination, including IgG levels, Fc-dependent effector functions, and MBC frequencies, were measured before and after vaccination in 40 PWH and 42 HIV-uninfected PW. Placental transfer of IgG and avidity were assessed in cord blood (CB). Soluble and cellular immune activation markers were quantified at baseline. FINDINGS: One month after vaccination, PWH had lower frequencies of MBC compared with HIV-uninfected PW. At delivery, PWH had attenuated pertussis-specific IgG levels and Fc-dependent effector functions. Reduced levels of maternal vaccine polyfunctional IgG and IgG avidity were transferred to HEU as compared to HIV-unexposed newborns. After adjustment with ethnicity, maternal antibody levels and gestational age at vaccination, HIV infection was independently associated with decreased levels of PT specific-IgG in CB. Both maternal and neonatal pertussis-specific IgG responses as well as PT-specific IgG avidity were inversely correlated with maternal sCD14 levels before vaccination among PWH. INTERPRETATION: Maternal HIV infection is associated with attenuated humoral immune responses to Tdap vaccination that correlate with sCD14. Suboptimal transfer of maternal immunity may further increase the risk of severe pertussis infection in HEU infants. FUNDING: This work was supported by IRIS Fund managed by the Foundation Roi Baudouin [2017J1820690206902], Association Vésale pour la Recherche Médicale and the Medical Council of CHU Saint-Pierre and has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, US Department of Health and Human Services, under Award No. U19AI145825. N.D. is a clinical researcher and A.M. is Research Director at the Fonds de la Recherche Scientifique (F.R.S.-FNRS), Belgium. M.E.A. was partially supported by NIHNIAID1U19AI14825. This article is published with the support of the Fondation Universitaire of Belgium.
Asunto(s)
Infecciones por VIH , Inmunoglobulina G , Células B de Memoria , Humanos , Femenino , Embarazo , Infecciones por VIH/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Adulto , Células B de Memoria/inmunología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Recién Nacido , Vacunación , Tos Ferina/inmunología , Tos Ferina/prevención & control , Afinidad de Anticuerpos/inmunologíaRESUMEN
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.
Asunto(s)
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
AIM/OBJECTIVE: This study investigates placental antibody transfer following recombinant pertussis vaccination in pregnancy in a real-world setting. METHODS: This postmarketing observational study recruited pregnant women vaccinated with monovalent recombinant acellular pertussis (aP) vaccine (aPgen; n = 199) or combined to tetanus-diphtheria (TdaPgen; n = 200), or Td-vaccine only (n = 54). Pregnancy, delivery, and neonatal outcomes were assessed. Cord blood was collected postdelivery and pertussis toxin (PT)-IgG, filamentous hemagglutinin (FHA)-IgG, and PT-neutralizing antibodies (PT-Nab) were assessed. RESULTS: No adverse pregnancy, delivery, or neonatal outcomes attributed to aPgen, TdaPgen, or Td vaccination were reported. High anti-PT antibody levels were detected in cord samples from women vaccinated with aPgen (geometric mean concentration [GMC] PT-IgG 206.1 IU/ml, 95% confidence intervals [CI]: 164.3-258.6; geometric mean titer [GMT] PT-Nab 105.3 IU/ml, 95% CI: 81.7-135.8) or TdaPgen (GMC PT-IgG 153.1 IU/ml, 95% CI: 129.1-181.5; GMT PT-Nab 81.5 IU/ml, 95% CI: 66.4-100.0). In the Td-only group, anti-PT antibodies were low (GMC PT-IgG 6.5 IU/ml, 95% CI: 4.9-8.8; GMT PT-Nab 3.8 IU/ml, 95% CI: 2.8-5.1). The same was found for FHA-IgG. Recombinant pertussis vaccination at <27 or 27-36 weeks gestation induced similar cord pertussis antibody levels. CONCLUSION: This first real-world study confirms that recombinant pertussis vaccination in the second or third trimester of pregnancy results in high levels of passive immunity in infants. Thai Clinical Trial Registry: TCTR20200528006.
Asunto(s)
Anticuerpos Antibacterianos , Inmunidad Materno-Adquirida , Tos Ferina , Humanos , Femenino , Embarazo , Adulto , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Tos Ferina/prevención & control , Tos Ferina/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Sangre Fetal/inmunología , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Vacuna contra la Tos Ferina/inmunología , Vacuna contra la Tos Ferina/administración & dosificación , Adulto Joven , Intercambio Materno-Fetal/inmunología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Recién Nacido , Toxina del Pertussis/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Bordetella pertussis/inmunología , VacunaciónRESUMEN
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.
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Anticuerpos Antibacterianos , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular , Inmunoglobulina G , Leche Humana , Tos Ferina , Humanos , Femenino , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Leche Humana/inmunología , Tos Ferina/prevención & control , Tos Ferina/inmunología , Inmunoglobulina G/sangre , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Embarazo , Adulto , Difteria/prevención & control , Difteria/inmunología , Tétanos/prevención & control , Tétanos/inmunología , Adulto Joven , Vacunación , Inmunidad Materno-Adquirida/inmunologíaRESUMEN
BACKGROUND: Global pediatric immunization programs with pneumococcal conjugate vaccines (PCVs) have reduced vaccine-type pneumococcal disease, but a substantial disease burden of non-PCV serotypes remains. METHODS: This phase 3, randomized (1:1), double-blind study evaluated safety and immunogenicity of 20-valent PCV (PCV20) relative to 13-valent PCV (PCV13) in healthy infants. Participants received 2 infant doses and a toddler dose of PCV20 or PCV13, with diphtheria-tetanus-acellular pertussis combination vaccine at all doses and measles, mumps, rubella and varicella vaccines at the toddler dose. Primary pneumococcal immunogenicity objectives were to demonstrate noninferiority (NI) of PCV20 to PCV13 for immunoglobulin G geometric mean concentrations after infant and toddler doses and percentages of participants with predefined serotype-specific immunoglobulin G concentrations after infant doses. Safety endpoints included local reactions, systemic events and adverse events. RESULTS: Overall, 1204 participants were vaccinated (PCV20, n = 601; PCV13, n = 603). One month after the toddler dose, 19/20 serotypes met NI for immunoglobulin G geometric mean concentrations; serotype 6B narrowly missed NI [PCV20/PCV13 geometric mean ratio: 0.57 (2-sided 95% confidence interval: 0.48-0.67); NI criterion: lower 2-sided 95% confidence interval >0.5]. Sixteen/twenty serotypes met NI for ≥1 primary objective after 2 infant doses. PCV20 induced robust opsonophagocytic activity, and boosting responses were observed for all vaccine serotypes, including those missing statistical NI. The safety/tolerability profile of PCV20 was like that of PCV13. CONCLUSIONS: PCV20 3-dose series in infants was safe and elicited robust immune responses. Based on these results and PCV13 experience, PCV20 3-dose series is expected to be protective for all 20 vaccine serotypes. NCT04546425.
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Anticuerpos Antibacterianos , Vacunas Neumococicas , Vacunas Conjugadas , Humanos , Vacunas Neumococicas/inmunología , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/efectos adversos , Lactante , Método Doble Ciego , Masculino , Femenino , Anticuerpos Antibacterianos/sangre , Vacunas Conjugadas/inmunología , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/efectos adversos , Inmunogenicidad Vacunal , Vacuna contra el Sarampión-Parotiditis-Rubéola/inmunología , Vacuna contra el Sarampión-Parotiditis-Rubéola/administración & dosificación , Vacuna contra el Sarampión-Parotiditis-Rubéola/efectos adversos , Infecciones Neumocócicas/prevención & control , Infecciones Neumocócicas/inmunología , Inmunoglobulina G/sangre , Vacuna contra la Varicela/inmunología , Vacuna contra la Varicela/efectos adversos , Vacuna contra la Varicela/administración & dosificación , Esquemas de Inmunización , Streptococcus pneumoniae/inmunología , Preescolar , 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 , Vacunas CombinadasRESUMEN
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.
Asunto(s)
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
El tétanos es causado por Clostridium tetani, bacteria Gram+ esporulada que produce una potente neurotoxina. Las vacunas parenterales producen IgG antitoxina tetánica (anti TT) protectores en múltiples dosis inductoras y de reactivación; vax-TET® es una vacuna cubana parenteral adsorbida en alúmina. La IgAS (secretora), principal anticuerpo protector mucoso, sólo es inducida por la vía mucosa. La vía oral, la inducción de IgA y su papel protector no han sido exploradas. SinTimVaS se aplica por vía mucosa y parenteral simultánea que induce IgG sistémica similares a la vía parenteral y adiciona de respuesta de IgA mucosa. Evaluamos el efecto de vax-TET® aplicado en SinTimVaS en ratones Balb/c y exploramos la influencia del adyuvante sobre la inducción de IgA anti TT. SinTimVaS indujo similares respuestas de IgG anti TT séricas que dos dosis de vax-TET® intramusculares; pero superiores a una dosis. Tres dosis de vax-TET® orales no indujeron IgG anti TT sérica, mientras que la adyuvación con el adyuvante Finlay Cocleato 1 (AFCo1) sí la indujeron. No se logró determinar la inducción de IgA anti TT mucosa con ninguna de las formulaciones adjuvadas con alúmina; pero si con la formulación AFCo1+TT. Podemos concluir que vax-TET® en SinTimVaS funcionó de forma similar a la inmunización parenteral establecida, por lo que sería posible reducir los esquemas multidosis con formulaciones de adyuvantes más potentes y se confirma que se requieren potentes adyuvantes para inducir IgA mucosa(AU)
Tetanus is caused by Clostridium tetani, a sporulated Gram+ bacterium that produces a potent neurotoxin. Parenteral vaccines produce protective tetanus antitoxin (anti TT) IgG in multiple induction and reactivation doses; vax-TET® is a Cuban parenteral vaccine adsorbed onto alumina. IgAS (secretory), the main mucosal protective antibody, is only induced by the mucous membrane. The oral route, the induction of IgA and its protective role have not been explored. SinTimVaS is applied by simultaneous mucosal and parenteral route that induces systemic IgG similar to the parenteral route and adds an IgA mucosal response. We evaluated the effect of vax-TET® applied in SinTimVaS in Balb/c mice and we explored the influence of adjuvant on the induction of anti-TT IgA. SinTimVaS induced similar serum anti TT IgG responses to two intramuscular doses of vax-TET®; but higher than one dose. Three doses of oral vax-TET® did not induce serum anti-TT IgG, whereas adjuvanted with adjuvant Finlay Cocleate 1 (AFCo1) did induce it. It was not possible to determine the IgA anti-TT mucous induction with any of the formulations adjuvanted with alumina; but with the formulation AFCo1 + TT it was induced. We can conclude that vax-TET® in SinTimVaS worked in a similar way to the established parenteral immunization, so it would be possible to reduce the multi-dose vaccination schemes with more potent adjuvant formulations and it is confirmed that powerful adjuvants are required to induce mucosal IgA(AU)
Asunto(s)
Humanos , Masculino , Femenino , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Medicamentos de Referencia , Vacunas , Estudios Prospectivos , Estudios Longitudinales , CubaRESUMEN
The aim of this study was to describe recent changes in the epidemiology of pertussis and existing policies regarding recommended and mandatory occupational vaccinations for healthcare professionals (HCPs). The authors carried out an extensive review of references on the PubMed and SciELO databases and the official sites of the World Health Organization, Pan American Health Organization, Centers for Disease Control and Prevention, and Brazilian Ministry of Health, using the keywords pertussis, vaccines and healthcare professionals. Vaccination against pertussis is recommended for HCPs in the United States, Canada, nine European countries, Australia, Hong Kong, Singapore, Costa Rica, Argentina and Uruguay, and in some countries it is compulsory. In Brazil, only one publication discussing the risk of pertussis among HCPs was found. Considering the reemergence of pertussis and the great number of associated hospitalizations and deaths registered in 2011, it is necessary to review public policies regarding HCP pertussis vaccination, particularly among workers in frequent contact with young babies.
O objetivo deste artigo é descrever as recentes mudanças na epidemiologia da pertússis e as políticas de vacinação voltadas à prevenção da coqueluche para profissionais de saúde. Os autores fizeram um levantamento dos artigos publicados no PubMed, SciELO e páginas da Internet da Organização Mundial da Saúde, Organização Pan-Americana da Saúde, Centers for Disease Control and Prevention (Estados Unidos) e do Ministério da Saúde usando as palavras-chave: pertussis, vacinas e profissionais de saúde. A vacinação de profissionais de saúde contra coqueluche é recomendada pela OMS, OPAS, CDC, e autoridades de saúde de nove países europeus, da Austrália, Hong Kong, Cingapura, Costa Rica, Argentina e Uruguai, e em alguns países é compulsória. No Brasil, identificamos apenas um artigo abordando a vacinação de profissionais de saúde contra coqueluche, mas considerando a reemergencia da doença com grande número de hospitalizações e mortes em 2011, consideramos necessário rediscutir as políticas públicas envolvendo a vacinação dos profissionais de saúde, particularmente daqueles que têm contato frequente com lactentes jovens.
El propósito de este artículo es describir los recientes cambios en la epidemiología y políticas de vacunación para la prevención de la tos ferina en los profesionales de la salud. Los autores realizaron un estudio de los artículos publicados en PubMed, sitios como SciELO, de la OMS, OPS, CDC y Ministerio de Salud de Brasil con las siguientes palabras clave: vacunas contra la tos ferina y profesionales de la salud. La vacunación de los trabajadores de la salud contra la tos ferina es recomendada por la OMS, la OPS, CDC y por las autoridades sanitarias de 9 países europeos, de Australia, Hong Kong, Singapur, Costa Rica, Argentina y Uruguay, y en algunos países es obligatoria. En Brasil, se ha identificado un solo artículo sobre la vacunación de los trabajadores de la salud contra la tos ferina, sin embargo, frente al resurgimiento de la enfermedad con un gran número de hospitalizaciones y muertes en 2011, consideramos que es necesario revisar la política pública de vacunación de los profesionales de la salud, especialmente si tienen contacto con niños pequeños.
Asunto(s)
Adulto , Humanos , Persona de Mediana Edad , Adulto Joven , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular , Personal de Salud , Transmisión de Enfermedad Infecciosa de Profesional a Paciente/prevención & control , Tos Ferina/transmisión , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Esquemas de Inmunización , Riesgos Laborales , Vacunación , Tos Ferina/epidemiología , Tos Ferina/inmunología , Tos Ferina/prevención & controlRESUMEN
La tos ferina sigue siendo responsable de una carga de enfermedad importante en el mundo. Aunque la implementación del uso de la vacuna contra esta enfermedad ha disminuido en gran medida el número de casos en la población pediátrica, se ha observado que la inmunidad inducida por la vacuna y por la infeccion natural disminuye con el tiempo lo que hace nuevamente susceptibles a adolescentes y adultos jóvenes que pueden transmitir la enfermedad a lactantes no inmunizados o con esquema de vacunación incompleto. Este documento, resultado de la reunión de un grupo internacional de expertos en la Ciudad de México, ha analizado la información médica reciente para establecer el estado actual de la epidemiología, diagnóstico, vigilancia y, especialmente, el valor de la dosis de refuerzo con dTpa en adolescentes y adultos como estrategia de prevención de tos ferina en México.
Pertussis continues to be responsible for a significant disease burden worldwide. Although immunization practices have reduced the occurrence of the disease among children, waning vaccine- and infection-induced immunity still allows the disease to affect adolescents and adults who, in turn, can transmit the disease to non-immunized or partially immunized infants. This document is the result of a meeting in Mexico City of international experts who analyzed recent medical information in order to establish the current status of the epidemiology, diagnosis and surveillance of pertussis and, especially, the value of the dTpa booster dose in adolescents and adults as a pertussis prevention strategy in Mexico.
Asunto(s)
Adolescente , Adulto , Niño , Preescolar , Humanos , Lactante , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular , Vacunación/normas , Tos Ferina/prevención & control , Anticuerpos Antibacterianos/sangre , Bordetella pertussis/genética , Bordetella pertussis/inmunología , Bordetella pertussis/aislamiento & purificación , ADN Bacteriano/sangre , Diagnóstico Diferencial , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Brotes de Enfermedades , Susceptibilidad a Enfermedades , Esquemas de Inmunización , Inmunización Secundaria , México/epidemiología , Infecciones del Sistema Respiratorio/diagnóstico , Factores de Tiempo , Tos Ferina/diagnóstico , Tos Ferina/epidemiología , Tos Ferina/microbiologíaRESUMEN
Objective: to discuss the current PAHO recommendation that does not support the substitution of traditional cellular DTP vaccine by acellular DTP, and the role of mutations, in humans, as the main cause of rare adverse events, such as epileptic-like convulsions, triggered by pertussis vaccine. Data review: the main components related to toxic effects of cellular pertussis vaccines are the lipopolysaccharide of bacterial cell wall and pertussis toxin. The removal of part of lipopolysaccharide layer has allowed the creation of a safer cellular pertussis vaccine, with costs comparable to the traditional cellular vaccine, and which may be a substitute for the acellular vaccine. Conclusion: The new methodology introduced by Instituto Butantan allows for the development of a new safer pertussis vaccine with low LPS content (Plow), and the use of the lipopolysaccharide obtained in the process in the production of monophosphoryl lipid A. This component has shown potent adjuvant effect when administered together with influenza inactivated vaccine, making possible to reduce the antigen dose, enhancing the production capacity and lowering costs.
Objetivo: Discutir as recomendações da WHO-OPAS que não consideram indicada a substituição da vacina DTP celular clássica pela DTP acelular e o papel de mutações, em humanos, como principal causa dos raros eventos de convulsões epileptiformes desencadeadas pela vacina pertussis. Revisão dos dados: Os principais componentes relacionados aos efeitos tóxicos da vacina pertussis celular são o lipopolissacarídio da parede celular da bactéria e a toxina pertussis. A remoção de parte da camada lipopolissacarídica permitiu a criação de uma vacina pertussis celular, mais segura e de custo comparável ao da vacina celular tradicional, podendo substituir a vacina pertussis acelular. Conclusão: A nova vacina pertussis, com baixo teor de LPS (Plow) desenvolvida pelo Instituto Butantan, além de oferecer uma vacina mais segura, permite o aproveitamento do lipopolissacarídeo para a produção de monofosforil lipídeo A. Esse componente mostrou-se potente como adjuvante e altamente eficiente quando administrado com a vacina de influenza, levando à possibilidade de se reduzir a dose de antígeno, aumentando a capacidade de produção e redução dos custos.
Asunto(s)
Humanos , Vacuna contra Difteria, Tétanos y Tos Ferina/efectos adversos , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/efectos adversos , Lipopolisacáridos/inmunología , Mutación , Análisis Costo-Beneficio , Vacuna contra Difteria, Tétanos y Tos Ferina/genética , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/genética , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Lipopolisacáridos/efectos adversos , Organización Mundial de la SaludRESUMEN
OBJECTIVE: To evaluate the immunogenicity of a combined DTPa-HB vaccine co-administered with Haemophilus influenzae type b conjugate vaccine (PRP-T) in Brazilian infants. MATERIAL AND METHODS: A prospective and open clinical study, in which 110 infants were immunized with a three-dose primary vaccination regime at two, four and six months of age and with a single booster vaccination. Blood samples were drawn immediately before the first dose, one month after the third dose, at the time of the booster dose and one month after the booster to assess seropositivity and antibody geometric mean titers (GMTs) of antibodies for diphtheria, tetanus, hepatitis B, Haemophilus influenzae type b and for the three pertussis antigens: Pertussis Toxin (PT), Filamentous Hemagglutinin (FHA) and Pertactin (PRN). RESULTS: Among the original 110 infants, 93 completed the study. Seropositivity was 100 percent for all seven involved antibodies, after the primary vaccination course. At the time of the booster dose, all antibodies (except diphtheria 33.7 percent and anti-PT 59 percent) were seropositive for more than 94 percent of subjects. After the booster, seropositivity increased to 100 percent for all antibodies. The GMT of these antibodies followed a similar pattern, with a strong increase after the primary course, followed by a second increase after the booster dose. At this time, GMT was2- to 7-fold higher than after the primary course, for all vaccine components. CONCLUSIONS: Concomitant administration of DTPa-HB and Hib vaccines elicited strong seroprotection for all the antigenic components. No interference with antibody response was evident. The vaccines provided high immunogenicity, following both the primary vaccinations and the booster dose.