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
BACKGROUND: Bordetella pertussis is the causative agent of whooping cough or pertussis. Although both acellular (aP) and whole-cell pertussis (wP) vaccines protect against disease, the wP vaccine, which is highly reactogenic, is better at preventing colonization and transmission. Reactogenicity is mainly attributed to the lipid A moiety of B. pertussis lipooligosaccharide (LOS). Within LOS, lipid A acts as a hydrophobic anchor, engaging with TLR4-MD2 on host immune cells to initiate both MyD88-dependent and TRIF-dependent pathways, thereby influencing adaptive immune responses. Lipid A variants, such as monophosphoryl lipid A (MPLA) can also act as adjuvants. Adjuvants may overcome the shortcomings of aP vaccines. RESULTS: This work used lipid A modifying enzymes from other bacteria to produce an MPLA-like adjuvant strain in B. pertussis. We created B. pertussis strains with distinct lipid A modifications, which were validated using MALDI-TOF. We engineered a hexa-acylated monophosphorylated lipid A that markedly decreased human TLR4 activation and activated the TRIF pathway. The modified lipooligosaccharide (LOS) promoted IRF3 phosphorylation and type I interferon production, similar to MPLA responses. We generated three other variants with increased adjuvanticity properties and reduced endotoxicity. Pyrogenicity studies using the Monocyte Activation Test (MAT) revealed that these four lipid A variants significantly decreased the IL-6, a marker for fever, response in peripheral blood mononuclear cells (PBMCs). CONCLUSION: These findings pave the way for developing wP vaccines that are possibly less reactogenic and designing adaptable adjuvants for current vaccine formulations, advancing more effective immunization strategies against pertussis.
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Adyuvantes Inmunológicos , Bordetella pertussis , Lípido A , Receptor Toll-Like 4 , Lípido A/análogos & derivados , Lípido A/inmunología , Bordetella pertussis/inmunología , Humanos , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/inmunología , Adyuvantes Inmunológicos/farmacología , Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Proteínas Adaptadoras del Transporte Vesicular/inmunología , Vacuna contra la Tos Ferina/inmunología , Lipopolisacáridos , Factor 3 Regulador del Interferón/metabolismo , Tos Ferina/prevención & control , Tos Ferina/inmunología , Interleucina-6/metabolismo , Interleucina-6/inmunologíaRESUMEN
Enzyme-linked immunosorbent assays (ELISA) are currently the method of choice for the serodiagnosis of pertussis and play a key role in the diagnosis of pertussis in adolescents and adults, as well as in epidemiological studies. In the present study, the in-house developed indirect ELISA was comparatively evaluated with six commercial kits from various manufacturers. Antipertussis antibodies were measured in 40 serum samples from patients with clinical symptoms of respiratory tract infection, in two WHO standards, and in seven human ECDC control sera. IgA and IgG antibodies were detected at a diagnostically significant level by different ELISA kits of 5.0% to 27.0% and 12.0% to 70.0% of patients' sera, appropriately. The analysis of results carried out with six commercial kits showed only 17.5% consistent results in class IgG (either clearly positive or negative). The average percentage of errors in the level of antibodies determined in the control samples, reference serum samples, differed quite significantly and ranged from 9.5% to 35.4% depending on the kit. This poor correlation of the results obtained on various serological tests intended for the serodiagnosis of pertussis may cause very serious diagnostic problems, especially when examining a serum sample obtained once during the course of the disease.
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Anticuerpos Antibacterianos , Bordetella pertussis , Ensayo de Inmunoadsorción Enzimática , Inmunoglobulina A , Inmunoglobulina G , Tos Ferina , Humanos , Ensayo de Inmunoadsorción Enzimática/métodos , Bordetella pertussis/inmunología , Anticuerpos Antibacterianos/sangre , Tos Ferina/diagnóstico , Tos Ferina/inmunología , Tos Ferina/sangre , Inmunoglobulina G/sangre , Adolescente , Inmunoglobulina A/sangre , Adulto , Niño , Sensibilidad y Especificidad , Pruebas Serológicas/métodos , Juego de Reactivos para Diagnóstico/normas , Preescolar , Adulto Joven , Femenino , MasculinoRESUMEN
BACKGROUND: Pertussis vaccination in pregnancy has been introduced in an increasing number of countries to better protect infants against the disease in their first weeks of life. The optimal timing of pertussis vaccination in pregnancy is however still under debate. METHODS: We systematically reviewed published literature on safety, immunogenicity and effectiveness of pertussis vaccination in pregnancy related to timing of vaccination. The search was conducted using PubMed, MEDLINE and Web of Science and yielded 1623 articles, thereof 777 duplicates. Screening resulted in the inclusion of 45 publications reporting on safety (n = 11), immunogenicity (n = 26) and/or effectiveness (n = 9). We also mapped pertussis recommendations in pregnancy by government institutions globally according to the recommended timing of vaccination. RESULTS: Overall, the selected publications did not indicate increased safety concerns associated with timing of pertussis vaccination in pregnancy. Immunogenicity studies often suggested optimal protection at birth after early third trimester vaccination. Few studies investigated qualitative antibody characteristics, and none investigated antibody titers in breastmilk or cellular-mediated immunity related to timing of vaccination. Effectiveness studies showed decreased vaccine effectiveness of late third trimester pertussis vaccination compared to vaccination earlier in pregnancy. Worldwide, a general recommendation for pertussis vaccination in pregnancy was found for 58 countries, with as many as 22 different recommended timings registered. CONCLUSION: The timing of pertussis vaccination in pregnancy seems to impact immunogenicity and vaccine effectiveness, with optimal immune responses at birth suggested following early third trimester vaccination and reduced vaccine effectiveness of late third trimester pertussis vaccination suggested compared to vaccination earlier in pregnancy. However, inconsistent and lacking data are reflected in the divergent national recommendations for pertussis vaccination in pregnancy worldwide. SUMMARY: Pertussis vaccination in pregnancy aims to protect infants in their first weeks of life. Our review suggests that immunogenicity and vaccine effectiveness are impacted by the timing of vaccination in pregnancy. National recommendations for pertussis vaccination in pregnancy vary widely worldwide.
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Vacuna contra la Tos Ferina , Vacunación , Tos Ferina , Humanos , Embarazo , Femenino , Tos Ferina/prevención & control , Tos Ferina/inmunología , Vacuna contra la Tos Ferina/administración & dosificación , Vacuna contra la Tos Ferina/inmunología , Vacunación/métodos , Esquemas de Inmunización , Eficacia de las Vacunas , Factores de TiempoRESUMEN
BACKGROUND: The reported number of pertussis cases declined after the implementation of COVID-19 prevention and control measures, however, the burden of pertussis among adults in China remains largely unknown. Additionally, the waning of natural antibody level has also rarely been assessed. METHODS: A total of 762 healthcare workers (HCWs) who had underwent the health examinations in 2021 and 2022 were included. Serum anti-PT IgG and IgA levels were determined by ELISA. Recent B. pertussis infection was defined as anti-PT IgG ≥100 IU/ml and/or anti-PT IgA ≥10 IU/ml. RESULTS: In 2021, the seroprevalence of recent B. pertussis infection was 10.1 %, and those HCWs in outpatient department had a higher percentage (18.6 %), and geometric mean concentration (GMC) (6.3 IU/ml) than those in other departments. This seroprevalence decreased to 2.4 % in 2022, although the difference remained significant. In the 77 subjects with recent B. pertussis infection in 2021, anti-PT IgG was undetectable in 18 cases the following year. Majority (68/76) of the subjects with anti-PT IgA ≥10 IU/ml in 2021 no longer had detected this antibody in 2022. Among 95 pertussis cases, approximately 60.0 % of cases reported no history of cough. Among those with a documented cough history, 36 cases with suspected pertussis courses who had never been diagnosed. Prolonged cough with nocturnal exacerbation (29/38) was the most commonly reported clinical symptom, and whoop was confirmed in six cases. Uroclepsia and syncopes during the cough attacks were reported by three and one subjects, respectively. One case presented with subconjunctival hemorrhage and tensionic purpura during the course. CONCLUSIONS: The results suggested a high prevalence of B. pertussis infection among HCWs. The presence of unrecognized adult pertussis cases and the rapid waning of antibody indicate the need to improve clinical management for suspected pertussis in adults, and to updated immunization schedule after childhood program.
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Anticuerpos Antibacterianos , Bordetella pertussis , COVID-19 , Personal de Salud , Inmunoglobulina G , Tos Ferina , Humanos , Estudios Seroepidemiológicos , Personal de Salud/estadística & datos numéricos , COVID-19/epidemiología , COVID-19/inmunología , China/epidemiología , Tos Ferina/epidemiología , Tos Ferina/inmunología , Tos Ferina/prevención & control , Adulto , Femenino , Masculino , Anticuerpos Antibacterianos/sangre , Inmunoglobulina G/sangre , Bordetella pertussis/inmunología , Persona de Mediana Edad , Inmunoglobulina A/sangre , SARS-CoV-2/inmunología , Adulto JovenRESUMEN
Continued circulation of the whooping cough pathogen, even in countries with high vaccine coverage, can be related to persistence of Bordetella pertussis biofilms in the respiratory tract. The films differ from planktonic cells by increased resistance to the host immune system and antibacterial drugs. The available acellular pertussis vaccines (aPV) containing antigens isolated from planktonic cultures of B. pertussis protect from severe forms of whooping cough, but do not effectively influence circulation of virulent strains in the subclinical forms of the disease and asymptomatic carriage. It is promising to create new generation aPV based on antigens isolated from biofilm cultures of B. pertussis capable of more effectively controlling the entire infectious cycle of whooping cough, including colonization, persistence, and transmission of the pathogen. From antigenic complexes isolated from the culture medium of biofilm and planktonic cultures of the strain B. pertussis No. 317 (serotype 1.2.3), experimental aPV were made: aPV-B and aPV-P, respectively. In intracerebral infection of mice with a virulent strain of B. pertussis, aPV-B demonstrated 2.5-fold higher protective activity than aPV-P and also more effectively reduced colonization of the lungs by B. pertussis cells in mice after intranasal infection with a virulent strain. Both vaccine preparations were safe and did not cause death in mice after administration of histamine.
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Biopelículas , Bordetella pertussis , Vacuna contra la Tos Ferina , Vacunas Acelulares , Tos Ferina , Bordetella pertussis/inmunología , Bordetella pertussis/patogenicidad , Vacuna contra la Tos Ferina/inmunología , Animales , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Tos Ferina/prevención & control , Tos Ferina/microbiología , Tos Ferina/inmunología , Ratones , Vacunas Acelulares/inmunología , Plancton/efectos de los fármacos , Plancton/inmunología , Antígenos Bacterianos/inmunología , Femenino , Ratones Endogámicos BALB C , Administración IntranasalRESUMEN
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 , InmunizaciónRESUMEN
Bordetella pertussis, the bacterium responsible for whooping cough, remains a significant public health challenge despite the existing licensed pertussis vaccines. Current acellular pertussis vaccines, though having favorable reactogenicity and efficacy profiles, involve complex and costly production processes. In addition, acellular vaccines have functional challenges such as short-lasting duration of immunity and limited antigen coverage. Filamentous hemagglutinin (FHA) is an adhesin of B. pertussis that is included in all multivalent pertussis vaccine formulations. Antibodies to FHA have been shown to prevent bacterial attachment to respiratory epithelial cells, and T cell responses to FHA facilitate cell-mediated immunity. In this study, FHA's mature C-terminal domain (MCD) was evaluated as a novel vaccine antigen. MCD was conjugated to virus-like particles via SpyTag-SpyCatcher technology. Prime-boost vaccine studies were performed in mice to characterize immunogenicity and protection against the intranasal B. pertussis challenge. MCD-SpyVLP was more immunogenic than SpyTag-MCD antigen alone, and in Tohama I strain challenge studies, improved protection against challenge was observed in the lungs at day 3 and in the trachea and nasal wash at day 7 post-challenge. Furthermore, a B. pertussis strain encoding genetically inactivated pertussis toxin was used to evaluate MCD-SpyVLP vaccine immunity. Mice vaccinated with MCD-SpyVLP had significantly lower respiratory bacterial burden at both days 3 and 7 post-challenge compared to mock-vaccinated animals. Overall, these data support the use of SpyTag-SpyCatcher VLPs as a platform for use in vaccine development against B. pertussis and other pathogens.
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Adhesinas Bacterianas , Anticuerpos Antibacterianos , Bordetella pertussis , Vacuna contra la Tos Ferina , Vacunas de Partículas Similares a Virus , Tos Ferina , Animales , Bordetella pertussis/inmunología , Ratones , Tos Ferina/prevención & control , Tos Ferina/inmunología , Vacuna contra la Tos Ferina/inmunología , Vacuna contra la Tos Ferina/administración & dosificación , Anticuerpos Antibacterianos/inmunología , Adhesinas Bacterianas/inmunología , Adhesinas Bacterianas/genética , Vacunas de Partículas Similares a Virus/inmunología , Vacunas de Partículas Similares a Virus/administración & dosificación , Femenino , Ratones Endogámicos BALB C , Factores de Virulencia de Bordetella/inmunología , Infecciones del Sistema Respiratorio/prevención & control , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/microbiologíaRESUMEN
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.
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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
Objective: The aim of this study was to examine the serum antibody levels against pertussis toxin (PT) in children experiencing an acute asthma attack and to explore the potential association between these levels and asthma. Methods: A prospective investigation was conducted, which involved 107 children with acute asthma attacks and 77 children diagnosed with bronchitis. The serum immunoglobulin G (IgG) antibody levels specific to PT were measured by using an in-house enzyme-linked immunosorbent assay. Based on the serum PT-IgG antibody levels, the children with asthma were categorized into three groups: non-pertussis infected, suspected pertussis infected, and recent pertussis infected. The clinical manifestations and pulmonary function of pediatric patients diagnosed with asthma were assessed and compared across various groups. Results: Of the total asthma group, 25 patients tested positive for PT-IgG, whereas only six patients in the bronchitis group were PT-IgG positive. The prevalence of recent pertussis infection was observed to be higher in the asthma group compared with the bronchitis group. Within the asthma group, those with recent pertussis infection exhibited a higher likelihood of experiencing wheezing and impaired lung function in comparison with the non-pertussis infection group. Conclusion: Pertussis infection is relatively common in children with asthma and correlates with the severity of asthma.
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Anticuerpos Antibacterianos , Asma , Inmunoglobulina G , Toxina del Pertussis , Tos Ferina , Humanos , Asma/inmunología , Asma/diagnóstico , Asma/sangre , Asma/epidemiología , Masculino , Femenino , Tos Ferina/inmunología , Tos Ferina/diagnóstico , Tos Ferina/sangre , Niño , Preescolar , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Anticuerpos Antibacterianos/sangre , Estudios Prospectivos , Toxina del Pertussis/inmunología , Enfermedad Aguda , Bordetella pertussis/inmunología , Adolescente , Pruebas de Función RespiratoriaRESUMEN
Objective: Pertussis cases have increased markedly since 2018 in Guangxi. The aim of this study was to evaluate antibody levels and the infection status of pertussis in the resident population. Method: A total of 10,215 serum samples from residents were collected from August-November 2018 and tested for anti-pertussis IgG and toxin IgG using the enzyme-linked immunosorbent assay (ELISA). Results: Of the collected samples, 1,833 (17.94%) tested positive for anti-pertussis IgG, with the median concentration of 16.06 IU/mL. Antibody level < 10 IU/mL accounted for more than 60% in children under 4 years of age, but declined with age, whereas the percentages of the other three levels (10-40, 40-50, and ≥ 50 IU/mL) increased almost with age ( P < 0.001). Moreover, 7,924 samples were selected for anti-pertussis toxin IgG, of which 653 (8.24%) tested positive (≥ 40 IU/mL) with the median concentration of 5.89 IU/mL, and 204 participants (2.56%) had recent pertussis infection (≥ 100 IU/mL). Among the different age groups, the highest rates of positivity and recent infection were observed at 11-20 years of age, the lowest positivity rate at 5 years of age, and the lowest recent infection rate at 4 years of age ( P < 0.001, P = 0.005, respectively). Conclusion: The survey results showed that all age groups in Guangxi lacked immunity against pertussis, which was one of the main factors contributing to the resurgence of pertussis in 2018. In addition, the prevalence of pertussis is relatively high in Guangxi, and its incidence is seriously underestimated, especially in adolescents and adults.
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Tos Ferina , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Lactante , Masculino , Persona de Mediana Edad , Adulto Joven , Distribución por Edad , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Bordetella pertussis/inmunología , China/epidemiología , Estudios Transversales , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Vacuna contra la Tos Ferina , Tos Ferina/epidemiología , Tos Ferina/inmunología , Tos Ferina/prevención & control , HumanosRESUMEN
INTRODUCTION: Whooping cough, also known as pertussis, remains a significant challenge as a vaccine-preventable disease worldwide. Since the switch from the whole-cell Pertussis (wP) vaccine to the acellular Pertussis vaccine (aP), cases of whooping cough have increased in countries using the aP vaccine. Understanding the immune system's response to pertussis vaccines and infection is crucial for improving current vaccine efficacy. AREAS COVERED: This review of the literature using PubMed records offers an overview of the qualitative differences in antibody and T cell responses to B. pertussis (BP) in vaccination and infection, and their potential association with decreased efficacy of the aP vaccine in preventing infection and subclinical colonization. We further discuss how asymptomatic infections and carriage are widespread among vaccinated human populations, and explore methodologies that can be employed for their detection, to better understand their impact on adaptive immune responses and identify key features necessary for protection against the disease. EXPERT OPINION: An underappreciated human BP reservoir, stemming from the decreased capacity of the aP vaccine to prevent subclinical infection, offers an alternative explanation for the increased incidence of clinical disease and recurrent outbreaks.
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Inmunidad Adaptativa , Bordetella pertussis , Vacuna contra la Tos Ferina , Vacunación , Tos Ferina , Humanos , Tos Ferina/prevención & control , Tos Ferina/inmunología , Vacuna contra la Tos Ferina/inmunología , Vacuna contra la Tos Ferina/administración & dosificación , Bordetella pertussis/inmunología , Inmunidad Adaptativa/inmunología , Vacunación/métodos , Eficacia de las Vacunas , Linfocitos T/inmunología , Anticuerpos Antibacterianos/inmunología , Anticuerpos Antibacterianos/sangre , AnimalesRESUMEN
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).
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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: Immunization against vaccine-preventable diseases prior to pregnancy is an important measure of primary prevention both for the mother and the unborn child. We analyzed immunity rates against measles, mumps, rubella, varicella, and pertussis in pregnant employees in Germany prior to significant changes in legal conditions in 2020, to provide a basis of comparison for future research. METHODS: We analyzed occupational-medical routine data in three collectives of pregnant women with an occupational risk of infection in the years 2018 and 2019: 1: hospital staff with regular access to an in-house company physician (n = 148); 2: employees in childcare with regular access to external occupational-health services (n = 139); 3: teachers with no regular access to occupational healthcare (n = 285). Immune status was assessed by a physician based on vaccination certificates, laboratory results, and medical documentation on prior infections. We compared immunity rates against measles, rubella, varicella, and pertussis as well as full immunity against all targeted vaccine-preventable diseases. RESULTS: Altogether, n = 572 pregnant women were included in our study. Of these women, 96.5 % were immune to rubella, 95.8 % to varicella, 88.3 % to measles, 82.7 % to mumps, and 67.8 % to pertussis. Only 56.2 % of the women had full immunity against all targeted vaccine-preventable diseases. Collective 1 showed the highest immunity rates against measles and pertussis as well as the highest rate of full immunity against all targeted vaccine-preventable diseases. The immunity rates against rubella and varicella did not differ significantly between the collectives. With the exception of rubella, the lowest immunity rates during pregnancy were found in Collective 3. CONCLUSION: We found pregnancy-relevant immunity gaps in all our study groups with significant differences between the collectives. Considering the potentially devastating consequences of infections during pregnancy, all medical professionals and health-policy makers should be involved in an increased effort to improve vaccination rates prior to pregnancy.
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Varicela , Sarampión , Rubéola (Sarampión Alemán) , Vacunación , Enfermedades Prevenibles por Vacunación , Humanos , Femenino , Alemania/epidemiología , Embarazo , Sarampión/prevención & control , Sarampión/inmunología , Adulto , Rubéola (Sarampión Alemán)/prevención & control , Rubéola (Sarampión Alemán)/inmunología , Varicela/prevención & control , Varicela/inmunología , Varicela/epidemiología , Enfermedades Prevenibles por Vacunación/prevención & control , Enfermedades Prevenibles por Vacunación/inmunología , Enfermedades Prevenibles por Vacunación/epidemiología , Paperas/prevención & control , Paperas/inmunología , Mujeres Embarazadas , Tos Ferina/prevención & control , Tos Ferina/inmunología , Adulto JovenRESUMEN
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.
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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
How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African ancestries. We undertook genetic analyses of vaccine antibody responses in infants from Uganda (n = 1391), Burkina Faso (n = 353) and South Africa (n = 755), identifying associations between human leukocyte antigen (HLA) and antibody response for five of eight tested antigens spanning pertussis, diphtheria and hepatitis B vaccines. In addition, through HLA typing 1,702 individuals from 11 populations of African ancestry derived predominantly from the 1000 Genomes Project, we constructed an imputation resource, fine-mapping class II HLA-DR and DQ associations explaining up to 10% of antibody response variance in our infant cohorts. We observed differences in the genetic architecture of pertussis antibody response between the cohorts with African ancestries and an independent cohort with European ancestry, but found no in silico evidence of differences in HLA peptide binding affinity or breadth. Using immune cell expression quantitative trait loci datasets derived from African-ancestry samples from the 1000 Genomes Project, we found evidence of differential HLA-DRB1 expression correlating with inferred protection from pertussis following vaccination. This work suggests that HLA-DRB1 expression may play a role in vaccine response and should be considered alongside peptide selection to improve vaccine design.
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Cadenas HLA-DRB1 , Femenino , Humanos , Lactante , Masculino , Formación de Anticuerpos/genética , Formación de Anticuerpos/inmunología , Población Negra/genética , Vacunas contra Hepatitis B/inmunología , Cadenas HLA-DRB1/genética , Cadenas HLA-DRB1/inmunología , Vacuna contra la Tos Ferina/inmunología , Vacuna contra la Tos Ferina/genética , Sitios de Carácter Cuantitativo , Uganda , Vacunación , Tos Ferina/prevención & control , Tos Ferina/inmunología , Tos Ferina/genética , Burkina Faso , Sudáfrica , Pueblo Africano , Pueblo EuropeoRESUMEN
PURPOSE: The resurgence of pertussis has occurred around the world. However, the epidemiological profiles of pertussis cannot be well understood by current diseases surveillance. This study was designed to understand the seroepidemiological characteristics of pertussis infection in the general population of Huzhou City, evaluate the prevalence infection of pertussis in the population, and offer insights to inform adjustments in pertussis prevention and control strategies. METHODS: From September to October 2023, a cross-sectional serosurvey was conducted in Huzhou City, involving 1015 permanent residents. Serum samples were collected from the study subjects, and pertussis toxin IgG antibodies (Anti-PT-IgG) were quantitatively measured using enzyme-linked immunosorbent assay (ELISA). The analysis included the geometric mean concentration (GMC) of Anti-PT-IgG, rates of GMC≥40IU/mL, ≥100IU/mL, and <5IU/mL. Stratified comparisons were made based on age, vaccination history, and human categories. RESULTS: Among the 1015 surveyed individuals, the geometric mean concentration (GMC) of Anti-PT-IgG was 10.52 (95% CI: 9.96-11.11) IU/mL, with a recent infection rate of 1.58%, a serum positivity rate of 11.43%, and a proportion with <5IU/mL of 40.49%. Among 357 children with clear vaccination history, susceptibility decreased with an increasing number of vaccine doses (Z = -6.793, P < 0.001). The concentration of Anti-PT-IgG exhibited a significant post-vaccination decline over time (Z = -5.143, P < 0.001). In women of childbearing age, the GMC of Anti-PT-IgG was 7.71 (95% CI: 6.90-8.62) IU/mL, with no significant difference in susceptibility among different age groups (χ2 = 0.545, P = 0.909). The annual pertussis infection rate in individuals aged ≥3 years was 9321 (95%CI: 3336-16039) per 100,000, with peak infection rates in the 20-29, 40-49, and 5-9 age groups at 34363 (95%CI: 6327-66918) per 100,000, 22307.72 (95%CI: 1380-47442) per 100,000, and 18020(95%CI: 1093-37266) per 100,000, respectively. CONCLUSIONS: In 2023, the actual pertussis infection rate in the population of Huzhou City was relatively high. Vaccine-induced antibodies exhibit a rapid decay, and the estimated serum infection rate increases rapidly from post-school age, peaking in the 20-29 age group. It is recommended to enhance pertussis monitoring in adolescents and adults and refine vaccine immunization strategies.
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Anticuerpos Antibacterianos , Inmunoglobulina G , Tos Ferina , Humanos , Tos Ferina/epidemiología , Tos Ferina/sangre , Tos Ferina/inmunología , Tos Ferina/prevención & control , Femenino , Estudios Transversales , Adulto , Masculino , China/epidemiología , Estudios Seroepidemiológicos , Niño , Persona de Mediana Edad , Adolescente , Preescolar , Adulto Joven , Lactante , Inmunoglobulina G/sangre , Anticuerpos Antibacterianos/sangre , Anciano , Toxina del Pertussis/inmunología , Prevalencia , Vacuna contra la Tos Ferina/inmunología , Vacunación , Bordetella pertussis/inmunologíaRESUMEN
Pertussis is a vaccine-preventable infectious disease; however, data on pertussis antibody levels in a nationwide population are still limited in China. We aimed to pool the seropositivity rates of IgG antibodies against pertussis toxin (PT-IgG) across the country. We systematically searched PubMed, Web of Science, Embase, and the China National Knowledge Infrastructure Database for studies published between January 1, 2010, and June 30, 2023. Studies reporting the seroprevalence of PT-IgG among a healthy Chinese population were included. Pooled estimates were obtained using random-effects meta-analyzes. The meta-analysis included 39 studies (47,778 participants) reporting anti-PT IgG seropositivity rates. The pooled rate for all ages was 7.06% (95% CI, 5.50%-9.07%). Subgroup analyzes showed rates ranging from 6.36% to 12.50% across different age groups. This meta-analysis indicated a low anti-PT IgG seropositivity rate in the Chinese population, particularly among school-aged children and young adults. This finding underscores the urgent need to refine immunization strategies.
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Anticuerpos Antibacterianos , Inmunoglobulina G , Toxina del Pertussis , Tos Ferina , Humanos , Estudios Seroepidemiológicos , Toxina del Pertussis/inmunología , Inmunoglobulina G/sangre , Tos Ferina/epidemiología , Tos Ferina/inmunología , Tos Ferina/prevención & control , China/epidemiología , Anticuerpos Antibacterianos/sangre , Niño , Adulto , Adulto Joven , Adolescente , Preescolar , Persona de Mediana Edad , Vacuna contra la Tos Ferina/inmunología , Vacuna contra la Tos Ferina/administración & dosificación , Pueblos del Este de AsiaRESUMEN
BACKGROUND: We recently reported a near disappearance of B. pertussis and a decline in anti-B. pertussis antibodies during the peak implementation of Coronavirus disease 2019 (COVID-19) non-pharmaceutical interventions (NPI) in 2021 in British Columbia (BC), Canada. During 2021-2023, incidence of reported B. pertussis cases remained low in BC at < 1/100,000 population. This study determined how serological evidence of B. pertussis changed after the gradual relaxation of NPI between 2021-2023. METHODS: Randomly selected blood samples from school staff 25-51 years old (n = 65) were collected yearly between 2021-2023 in the Vancouver metropolitan area, BC, Canada, and tested for anti-pertussis toxin (PT) IgG levels. Serological evidence of B. pertussis infection (thereafter "seroconversion") was defined as a quantifiable anti-PT IgG levels in subjects with anti-PT IgG levels below lower limit of quantification in the preceding year or a > 4-fold increase in anti-PT IgG levels between two subsequent years. Samples were also tested for anti-diphtheria toxoid (DT) IgG, and similar seroconversion criteria were applied to exclude seroconversion due to vaccination with tetanus-diphtheria-acellular-pertussis (Tdap). RESULTS: Three subjects met seroconversion criteria for anti-PT IgG between 2021 and 2022 and 9 between 2022 and 2023, yielding a seroconversion rate of 4.6 /100 person-years and 14.9/100 person-years, P = 0.127, respectively. None of the subjects met the criteria for vaccination with Tdap. The geometric mean concentration of anti-PT IgG showed a statistically significant decrease in 2022 compared with 2021, 4.8 IU/mL IU/ml (95 % confidence interval [CI], 3.8-5.9) vs. 6.4 IU/ml (95 % CI, 4.9-8.2; p = 0.001), followed by a statistically significant increase in 2023 compared with 2022 6.5 IU/ml (95 % CI, 4.9-8.5) vs. 4.8 IU/ml (95 % CI, 3.8-5.9; p = 0.0006), respectively. DISCUSSION: Serological evidence of B. pertussis increased between 2022 and 2023 despite low reported cases, which suggests that B. pertussis circulation resumed after relaxing of COVID-19 NPI.