Low levels of detectable pertussis antibody among a large cohort of pregnant women in Canada

Newborns and infants less than 6 months of age continue to be at highest risk of severe outcomes from pertussis infection. Pertussis vaccination during the last trimester of pregnancy can confer protection to newborns as a result of trans-placental transfer of pertussis antibodies. In several countries, pertussis vaccination in pregnancy is recommended routinely and Canada’s National Advisory Committee on Immunization issued similar routine recommendations in February 2018. Using second trimester biobanked plasma samples (n = 1752) collected between 2008 and 2011, we measured the pre-existing anti-pertussis toxin (PT) levels in a large cohort of second-trimester pregnant women using a commercial ELISA test. We found that 97.5% of these women had anti-PT IgG titres below 35 IU/mL. Women with higher incomes had slightly higher anti-PT levels but 96% still had titres <35 IU/ml. In conclusion, almost all of the pregnant women in this large cohort had anti-PT levels low enough to suggest susceptibility to pertussis infection in both the mothers and their newborn infants.     

Anti-pertussis antibody kinetics following DTaP-IPV booster vaccination in Norwegian children 7–8 years of age

At the age of 7–8 years a booster of diphtheria, tetanus, acellular pertussis and polio vaccine is recommended for children in Norway. In this cross-sectional study we have analysed the antibody levels against pertussis vaccine antigens in sera from 498 children aged 6–12 years. The purposes of this study were to investigate the duration of the booster response against the pertussis vaccine antigens pertussis toxin (PT) and filamentous haemagglutinin (FHA); to determine the presence of high levels of pertussis antibodies in absence of recent vaccination; and to analyse how booster immunisation may interfere with the serological pertussis diagnostics. Prior to the booster the IgG antibody levels against PT revealed a geometric mean of 7.3 IU/ml. After the booster the geometric mean peak anti-PT IgG response reached to 45.6 IU/ml, followed by a steady decline in antibody levels over the next few years. The IgG anti-FHA levels followed the anti-PT IgG profiles. Three years after the booster the geometric mean IgG levels were only slightly above pre-booster levels. Prior to the booster 44% of the sera contained ≤5 IU/ml of anti-PT IgG compared to18% 3 years after and 30% 4 years after the booster. When recently vaccinated children were excluded, 6.2% of the children had anti-PT IgG levels above 50 IU/ml which may indicate pertussis infection within the last 2 years. This study indicates that the currently used acellular pertussis vaccines induce moderate immune responses to the pertussis antigens and that the antibodies wane within few years after the booster. This lack of sustained immune response may partly be responsible for the increased number of pertussis cases observed in this age group during the last years.     

Seroprevalence of Bordetella pertussis antibodies and anti-pertussis antibody response after a single dose of reduced-antigen combined diphtheria,tetanus, and acellular pertussis vaccine (Tdap) in pregnant Thai women

BackgroundMaternal immunization with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) has recently been implemented to prevent infant pertussis. Tdap is still not routinely recommended in Thailand, and there are limited data to support or challenge this strategy.ObjectivesThe primary aim was to determine the seroprevalence of anti-pertussis toxin antibodies (anti-PT IgG) among pregnant Thai women. The secondary aims were to evaluate antibodies response after Tdap vaccination between seronegative and seropositive mothers and to compare the different antibody titers at delivery among seropositive mothers who received Tdap to those who received tetanus-diphtheria vaccine (Td).MethodsThis randomized clinical trial was conducted during April 2018 to April 2019 at Siriraj Hospital, Bangkok, Thailand. A total of 129 pregnant women were included. Paired blood samples for anti-PT IgG levels were obtained during the first antenatal visit and at delivery. A baseline cut-off value of <5 IU/ml indicated seronegativity. There were 29 exclusions from the original 129 enrollment. All seronegative participants (n = 69) received Tdap, while the seropositive group were randomized 1:1 to receive either Tdap (n = 18) or Td (n = 13) during 27–36 weeks’ gestation. The antibody levels from both sera were compared between groups.ResultsThe seroprevalence of maternal anti-PT IgG was 33.3% (43/129). There was no significant difference in the increment of antibody levels after Tdap vaccination between the seronegative and seropositive groups (30.2 vs. 42 IU/ml; p = 0.183). Among seropositive groups, all Tdap recipients had increased antibody titers at delivery, while all Td recipients showed waning of immunity throughout gestation. (42 IU/ml vs. −7.4 IU/ml; p < 0.001).ConclusionMost pregnant Thai women have seronegative against pertussis. Most seropositive mothers had initial low antibody titers and their immunity significantly decreased before delivery. Our findings highlight the need for universal pertussis immunization in pregnancy regardless of individual baseline immunity.     

Combined tetanus-diphtheria and pertussis vaccine during pregnancy: transfer of maternal pertussis antibodies to the newborn

Background and objectivesPertussis is currently an emerging public health concern in some countries with high vaccination coverage. It is expected that maternal pertussis immunization could provide newborn protection. We compared pertussis toxin antibody (anti-PT) levels in women during pregnancy (pre- and post-vaccination) with respect to levels in the newborn at delivery in women vaccinated during pregnancy. We also estimated anti-PT titers at primary infant vaccination.MethodsObservational study of pregnant women vaccinated with Tdap (≥20 weeks gestation) and their newborns between May 2012 and August 2013. Anti-PT levels were determined by ELISA in maternal (pre- and post-vaccination) and newborn blood.ResultsPre-vaccination, post-vaccination maternal and newborn samples were available in 132 subjects. Mean maternal age was 34.2 (SD 4.3) years. Median weeks of gestation at vaccination were 27.2 (Q1–Q3 21.7–30.8). Anti-PT (≥10 IU/ml) levels were found in 37.1% of maternal pre-vaccination samples (geometric mean titer (GMT) 7.9 IU/ml (95% CI 6.8–9.2)), 90.2% of post-vaccination samples (GMT 31.1 IU/ml (95% CI 26.6–36.3)) and 94.7% of newborns (GMT 37.8 IU/ml (95% CI 32.3–44.1)). The Lin concordance index between post-vaccination maternal and newborn samples was 0.8 (95% CI 0.8–0.9). Transplacental transfer ratio was 146.6%. At two months of age, 66% of newborns had estimated anti-PT levels ≥10 IU/ml.ConclusionsThere was a high correlation between anti-PT levels in mothers and newborns, with higher levels in newborns, which should be sufficient to provide protection against pertussis during the first months of life. Vaccination of pregnant women seems to be an immunogenic strategy to protect newborns until primary infant immunization.     

Pertussis vaccination during pregnancy in Belgium: Follow-up of infants until 1 month after the fourth infant pertussis vaccination at 15 months of age

Vaccination of pregnant women with a pertussis containing vaccine is a recommended strategy in some industrialized countries, to protect young infants from severe disease. One of the effects of the presence of high titers of passively acquired maternal antibodies in young infants is blunting of immune responses to infant vaccination. We present infant immune responses to a fourth pertussis containing vaccine dose at 15 months of age, as a follow-up of previously presented data.In a prospective cohort study, women were either vaccinated with an acellular pertussis vaccine (Boostrix^®) during pregnancy (vaccine group) or received no vaccine (control group).All infants were vaccinated with Infanrix Hexa^® according to the standard Belgian vaccination schedule (8/12/16 weeks, 15 months). We report results from blood samples collected before and 1 month after the fourth vaccine dose. Immunoglobulin G (IgG) antibodies against pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (Prn), tetanus toxoid (TT) and diphtheria toxoid (DT) were measured using commercially available ELISA tests. Antibody levels were expressed in International Units per milliliter.Demographic characteristics were similar in the vaccine and control group. Before the fourth vaccine dose, significantly lower antibody titers were measured in the vaccine group compared to the control group for anti-Prn IgG (p = 0.003) and anti-DT IgG (p = 0.023), with a steep decay of antibody titers since post-primary vaccination. One month after the fourth dose, antibody titers were only significantly lower in the vaccine group for anti-PT IgG (p = 0.006). For all antigens, there was a rise in antibody titer after the fourth vaccine dose.The present results indicate still a minor blunting effect 1 month after a fourth vaccine dose for anti-PT antibodies. However, a good humoral immune response on all measured antigens was elicited in both groups of children. The clinical significance of such blunting effect is yet unknown.Clinicaltrials.gov identifier: NCT01698346.     

Seroepidemiology of pertussis in China: A population-based,cross-sectional study

BackgroundDespite high pertussis vaccination coverage and significant decrease of pertussis since the adoption of the Expanded Programme on Immunization (1978), increased pertussis incidence has been reported in China from 2013 to 2017. This study aimed at evaluating the immune response to pertussis among vaccinated children and beyond in China.MethodsThe study recruited 2 144 healthy subjects. Serum IgG antibodies against pertussis toxin (anti-PT IgG) were measured by ELISA. Anti-PT IgG concentration (GMC), seropositivity rate (GMC ≥ 40 IU/ml), and recent infection rate (GMC > 100 IU/ml) were calculated. Participants ≤ 2 years-old were further stratified by vaccination schedule intervals and participants ≤ 6 years-old by vaccine used (Domestic DTaP or DTaP-IPV//PRP ~ T (Pentaxim, SP)).ResultsAmong 0–6-year-olds, the anti-PT IgG GMC was 5.99 IU/ml (95%CI 5.39–6.67). The GMC increased in accordance with the primary vaccination series (4–6 months) and the toddler booster (18–23 months), and continuously declined thereafter to its nadir at 6 years-old [3.72 IU/ml (95%CI 2.91–4.77)]. GMCs were markedly higher in those vaccinated with DTaP-IPV/PRP ~ T compared to DTaP. In individuals > 6 years-old, the GMC was 5.67 IU/ml (95%CI 5.36–6.00), the seropositivity rate was 6.7% (95%CI 5.5–7.9) and the recent infection rate was 1.2% (95%CI 0.7–1.7). The seropositivity rates increased from 6 years-old and peaked at 9 years-old (10.3% [95%CI 0.7–19.8]).ConclusionsVaccination against pertussis increases anti-PT IgG, but wanes over time. The sero-estimated infection rates increase from school age and peak at about 9 years-old. These results support the addition of a booster of pertussis vaccine at preschool age.     

Elucidating the difference in the kinetics of antibody titres of infants in Belgium and Vietnam

Serological results obtained in a single laboratory from twin-studies on maternal immunisation, in Vietnam and Belgium offer the opportunity to compare antibody kinetics in infants before and after infant vaccination in the presence of vaccine-induced maternal antibodies. Nonlinear mixed-effects models (NLMMs) making use of a hypothesised dynamic evolution that captures the change in antibody titres over time, were employed to model anti-PT and anti-Prn antibody dynamics. Our proposed modelling approach provided useful insight into understanding the differences in the infants’ antibody kinetics in both countries since NLMMs offer the possibility of pooling all data in one analysis and incorporate relevant covariates of interest.In both controlled cohort studies, pregnant women were vaccinated with a tetanus, diphtheria, acellular pertussis (Tdap) vaccine (Boostrix®, Belgium; Adacel®, Vietnam), and children were followed before and after primary vaccination, and before and after booster vaccination (Infanrix hexa®). From our models, both anti-PRN and anti-PT antibody titres at birth of Vietnamese infants were significantly lower than those of Belgian infants born to vaccinated women groups. Even though the antibody titres in the cord at birth of Belgian infants were also higher than those of Vietnamese infants born to the control women groups, the difference was not significant. The significant difference between infants born to vaccinated women in the two countries was likely due to the use of different vaccine brands in pregnant women and the different vaccination histories of women in these two countries.Our analyses also suggested that the blunting effect was present during the primary immunisation but went away afterward for anti-PT data. In contrast, for anti-PRN antibodies, the blunting effect persisted after the primary vaccination and possibly went away after the booster dose. Countries should be aware of the regional situation in view of recommending maternal immunization.     

Association between the timing of maternal vaccination and newborns’ anti-pertussis toxin antibody levels

BackgroundPertussis remains an important global public health concern, despite the presence of extensive immunization programs. Incidence and severity of pertussis are typically higher in neonates and young infants. As a strategy to protect these young infants, maternal vaccination with Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) has been recommended in Brazil. The objective of this study was to evaluate the effects of Tdap vaccination during pregnancy on the anti-pertussis toxin (PT) IgG response in mothers and their infants at birth.Material and methodsMaternal and cord blood samples were collected from vaccinated (n = 243) and unvaccinated (n = 75) pregnant women, at the time of delivery, from July 2015 to August 2016 in São Paulo, Brazil. Anti-PT IgG antibodies were quantified by Enzyme-Linked Immunosorbent Assay (ELISA) and geometric mean concentrations (GMC) were calculated. Relationship between timing of vaccination and antibody concentrations were evaluated.ResultsMaternal and cord blood GMCs among the vaccinated group were 5.4 and 5.6 fold higher [66.5 International Units (IU)/mL and 89.8 IU/mL] compared to the unvaccinated group (12.4 IU/mL and 16.1 IU/mL), respectively (p < 0.001). Higher anti-PT IgG GMCs were observed when vaccination occurred ≥60 days before delivery compared to <60 days, suggesting that vaccination early in the third trimester may be more effective than later in pregnancy.ConclusionTdap maternal vaccination results in significantly higher anti-PT IgG in newborn infants and supports the current recommendation of the Brazilian Immunization Program.     

Determination of circulating antibodies directed to pertussis toxin and of agglutinogens in children vaccinated with either the whole cell or component pertussis vaccine in France, Japan and Senegal.

The antibody response to pertussis toxin (PT) and agglutinogens of children vaccinated in Japan, France and Senegal with either whole cell or component pertussis vaccine was determined at various times after immunization. Agglutinin titres were almost similar in sera of Japanese children vaccinated with either whole cell or component pertussis vaccine whereas anti-PT antibody levels were found to be higher after vaccination with whole cell vaccine than with component vaccine. The geometric mean (GM) agglutinin titres in sera of Japanese children amounted to 45.0 and 45.7, respectively, and neutralization GM titres to 71.6 and 22.6, respectively, following vaccination with the whole cell and component pertussis vaccines. Sera of French children receiving three doses of whole cell vaccine exhibited a GM agglutinin titre of 17.8, whereas only 16% of sera contained neutralizing antibodies against PT. Following the booster dose the GM agglutinin titre rose to 213.5 and 68% of the sera contained neutralizing antibodies to PT (GM titre 48.0). Sera of Senegalese children receiving three doses of whole cell vaccine exhibited a GM agglutinin titre of 18.7, whereas anti-PT neutralizing antibodies were hardly detected. Agglutinins and anti-PT antibody in sera of French and Senegalese children turned out to be lower than were found 25 years ago in sera of children immunized with the French whole cell pertussis vaccine.     

The decline in immunity and circulation of pertussis among Chinese population during the COVID-19 pandemic: A cross-sectional sero-epidemiological study

BackgroundIn recent years, the resurgence of pertussis has posed a public health challenge in many countries. This study aimed to evaluate the immunity levels against pertussis among populations of different ages in China.MethodsWe conducted a cross-sectional serological survey in Zhejiang Province, China in 2020. Serum IgG antibodies against pertussis toxin (anti-PT), filamentous hemagglutinin (anti-FHA), and pertactin (anti-PRN) were quantitatively measured. The geometric mean concentration (GMC) of three antibodies was calculated. An anti-PT level < 5 IU/mL was considered undetectable, ≥20 IU/mL as seropositive and ≥80 IU/mL as an indicator of recent infection. Mathematical models were fitted for anti-PT concentrations over time in children after four doses of the pertussis vaccination.ResultsA total of 4459 participants aged 0–59 years were included in the analyses. The overall positivity rate of anti-PT was 29.80% with the highest (81.44%) rate in the 1–2 years old and the lowest (4.72%) in 10–14 years old. The GMCs of anti-PT, anti-FHA and anti-PRN for the whole participants were 9.67 (95%CI: 9.25–10.10),18.93 (18.24–19.67), and 8.99 (8.61–9.38) IU/mL, respectively. Over 50% of subjects aged ≥ 7 years had undetectable anti-PT IgG antibodies (<5IU/mL). The proportions of the populations with anti-PT IgG ≥ 80 IU/mL were approximately 0.9%, 0.3% and 1.1% among the 10–14, 15–29, and 40–59 years old groups, respectively. The power regression equation of the attenuation model after last dose of pertussis vaccine was y = 41.088x^-1.238 (R² = 0.935, p < 0.001). The fitted anti-PT concentrations was only 5.60 IU/mL at 5 years following the last vaccination dose.ConclusionThe prevalence of pertussis decreased during the study period in the COVID-19 pandemic; however, there was still a certain proportion of adolescents and adults with evidence of recent infection. The decline in antibody levels after pertussis vaccination was observed, and booster doses are in urgent need in China.     

Immunogenicity of a liquid hexavalent DTaP-IPV-HB-PRP∼T vaccine after primary and booster vaccination of term and preterm infants born to women vaccinated with Tdap during pregnancy

BackgroundVaccination during pregnancy with tetanus, diphtheria, acellular pertussis (aP) (Tdap) antigens is important for early protection of newborn infants against pertussis, particularly for preterm infants. This study evaluated the effect of Tdap vaccination during pregnancy on the immunogenicity of a diphtheria (D), tetanus (T), aP, inactivated poliovirus (IPV), hepatitis B (HB), and Haemophilus influenzae type b (PRP ～ T) vaccine in term and preterm populations.MethodsA prospective, observational study (NCT02511327) recruited women and their infants based on delivery (term or preterm) and vaccination status (vaccinated with a Tdap vaccine [Boostrix?, GlaxoSmithKline] during pregnancy or not vaccinated in the last 5 years). All infants received licensed DTaP-IPV-HB-PRP ～ T (Hexyon?, Sanofi) (8, 12, 16 week primary series and booster at 13 months of age [preterm infants] or 15 months of age [term infants]). Immunogenicity was evaluated using validated assays. Data were pooled into term (N = 127) and preterm infants (N = 105), and infants of women who received a Tdap vaccine during pregnancy (N = 199) or not (N = 33).ResultsBefore primary vaccination, antibody levels were higher for term than preterm infants for anti-D, anti-polio 1, 2, 3, anti-PT, anti-FHA, and anti-PRP, and similar for anti-HBs and anti-T. At this time, infants of Tdap-vaccinated women had higher anti-D, anti-T, anti-PT, anti-FHA, and anti-PRP antibody levels than infants of Tdap-unvaccinated women; anti-HBs and anti-polio antibody levels were similar in both groups. Post-primary, pre-booster, and post-booster, there were only small differences in seroprotection rates (anti-D, anti-T, anti-polio 1, 2, 3, anti-HBs, anti-PRP) and seroconversion rates (anti-PT, anti-FHA), except for anti-HBs ≥ 10 mIU/mL and anti-PRP ≥ 0.15 µg/mL post-primary vaccination (higher for term [98.31 % and 90.91 %, respectively] versus preterm infants [89.80 % and 79.41 %, respectively]).ConclusionsThese data support the use of DTaP-IPV-HB-PRP ～ T vaccine for primary and booster vaccination in term and preterm born infants and in infants born to Tdap-vaccinated or Tdap-unvaccinated women.     

Humoral and cell mediated immune responses to a pertussis containing vaccine in pregnant and nonpregnant women

Vaccination of pregnant women is recommended for some infectious diseases in order to protect both women and offspring through high titres of maternal IgG antibodies. Less is known on the triggering of cellular immune responses by vaccines administered during pregnancy. In an ongoing study on maternal pertussis vaccination (2012–2014) 18 pregnant women were vaccinated with a tetanus-diphtheria-acellular pertussis (Tdap) containing vaccine (Boostrix®) during the third pregnancy trimester. Sixteen age-matched nonpregnant women received the same vaccine in the same time period. A blood sample was taken at the moment of, but before vaccination and one month and one year after vaccination. Anti-Pertussis Toxin (PT), filamentous hemagglutinin (FHA), pertactin (Prn), tetanus toxin (TT) and diphtheria toxin (DT) antibodies were measured by ELISA. Cellular immune responses were analyzed using a diluted whole blood assay, measuring proliferation, and cytokine release in response to vaccine antigens PT, FHA, TT, and to pokeweed mitogen (PWM) as polyclonal stimulus.Antibody levels to all five vaccine components increased significantly and to the same extent after vaccination in pregnant and nonpregnant women. One year after vaccination, antibody titres had decreased particularly to PT, but they were still significantly higher to all antigens than before vaccination. In contrast, proliferative and IFN-γ responses were increased to TT, PT, and FHA in nonpregnant women one month after vaccination, whereas in pregnant women only TT specific T cell responses were increased and to a lesser extent than in the control group. One year after vaccination, cellular responses equaled the baseline levels detected prior to vaccination in both groups. In conclusion, a Tdap vaccination can increase vaccine specific IgG antibodies to the same extent in pregnant and in nonpregnant women, whereas the stimulation of vaccine specific Th1 type cellular immune responses with this acellular vaccine is transient and impaired during pregnancy.     

Seroprevalence of IgG antibodies to pertussis toxin in children and adolescents in Estonia

Background and aims

Despite high immunisation coverage and frequent booster doses, the national notification rates of pertussis in Estonia have been increasing. The peak of 97/100,000 was reached in 2010 which is the highest incidence rate since 1962 (210/100,000).We aimed to measure the prevalence of pertussis toxin (PT) IgG type antibodies in subjects of <18 years and to estimate the pertussis infection activity in a recently non-immunised cohort.

Methods

In a cross-sectional serosurvey, all consecutive leftover sera were collected in the Tartu University Hospital during April–August 2012. Anti-PT IgG concentration was measured by commercial ELISA and analysed in yearly cohorts. The antibody concentrations ≥62.5 IU/mL was considered suggestive to pertussis in the last year among 9- to 14-year-olds.

Results

The GMC of the anti-PT-IgG was 7.4 IU/mL (95% CI 6.9–8.0). In the total of 1053 serum samples, the highest proportion of sera with high antibody titres ≥125 IU/mL and ≥62.5 IU/mL were at the ages when pertussis vaccine boosters were given: 7 years 10.9% (95% CI 4.1–22.3) and 2 years 36.9% (95% CI 25.3–49.8), respectively. Approximately half of all sera had undetectable anti-PT IgG levels. The estimated incidence of Bordetella pertussis infection among 9- to 14-year-olds in the year before serum sampling was 6.3% (95% CI 3.3–10.8), which is at least 60 times higher than the officially reported incidence of pertussis disease in respective years.

Conclusions

The serologic method is not suitable for diagnosing pertussis in instances when the last pertussis immunisation was less than one year ago. The relatively high proportion of subjects with undetectable anti-PT IgG levels and the relatively low rate of officially reported pertussis cases suggest that low antibody levels do not necessarily indicate the absence of protection. The estimated incidence rate of pertussis is much higher than officially reported figures, which suggests that asymptomatic/mild B. pertussis infection remains unrecognised and unreported.     

健康成人抗百日咳毒素和抗百日咳丝状血凝素抗体检测与分析

目的评估健康成人抗百日咳毒素(anti-PT)和抗百日咳丝状血凝素(anti-FHA)抗体水平。方法选择20-59岁健康成人,采用改良ELISA(mELISA)、改良硫氰酸铵-ELISA分别测定血清anti-PT和anti-FHA IgG抗体的浓度、亲和力,分析二者的相关性;采用CHO细胞簇集试验测定anti-PT中和抗体滴度,分析与anti-PT IgG抗体浓度的相关性。结果共纳入研究对象73名,anti-PT、anti-FHA IgG抗体几何平均浓度(GMC)分别为10.4 IU/mL、58.2 IU/mL,抗体亲和力中位数分别为34.8%、61.4%,anti-PT中和抗体几何平均滴度(GMT)为1:27.3。anti-PT、anti-FHA IgG抗体的浓度与亲和力均呈正相关(r=0.45,P<0.01;r=0.76,P<0.01);anti-PT中和抗体滴度与浓度呈正相关(r=0.77,P<0.01)。结论健康成人anti-PT抗体水平较低,建议制定成人百日咳疫苗免疫程序;mELISA可替代CHO细胞簇集试验用于百日咳血清学检测。     

Analogous IgG subclass response to pertussis toxin in vaccinated children,healthy or affected by whooping cough

The study of antigen specific IgG subclass distribution during disease, or during any other natural or artificial immunisation, can provide useful information on the kind of the immune response and the expected levels of protection. This is particularly true for diseases, such as pertussis in which the mechanisms underlying specific defence are still not completely understood. An investigation was therefore performed to evaluate the IgG subclass response to pertussis toxin (PT) in sera from 89 healthy vaccinated children and 131 vaccinated or unvaccinated children convalescent after a confirmed B. pertussis symptomatic infection. Antibody titres were expressed in arbitrary ELISA units/ml, and statistical analyses were performed. In unvaccinated convalescent children IgG1 and IgG3 were prevalent whereas in children immunised with two different acellular pertussis (aP) vaccines, both healthy and convalescent, IgG1, IgG2 and IgG4 antibodies were mainly produced. Maintenance of the same anti-PT antibody response pattern in healthy acellular pertussis vaccine recipients and in vaccinated children who later acquire the disease is an interesting result indicative of the priming effect induced by these vaccines in the direction of a relatively higher Th2 cell-polarisation of the immune response.     

江苏省2018年健康人群百日咳毒素和丝状血凝素IgG抗体水平调查

目的了解江苏省2018年健康人群百日咳毒素(Pertussis toxin,PT)和丝状血凝素(Filamentous hemagglutinin,FHA)IgG抗体水平。方法采用分层抽样在江苏省两个市选择7个年龄组健康人群,采用间接酶联免疫吸附试验检测血清PT IgG抗体(IgG antibody against PT,Anti-PT IgG)和FHA IgG抗体(IgG antibody against FHA,Anti-FHA IgG),分析抗体阳性(抗体浓度≥20IU/mL)率和几何平均浓度(Geometricmeanconcentration,GMC)。结果共纳入受试者752名,Anti-PT IgG、Anti-FHA IgG阳性率分别为14.76%、28.72%,GMC分别为12.37IU/mL、17.13IU/mL。各年龄组Anti-PT IgG阳性率在8.62%(3-5岁)-23.15%(10-14岁)之间(χ^2=15.59,P<0.05),Anti-FHAIgG阳性率在10.38%(0-1.4岁)-53.27%(10-14岁)之间(χ^2=57.50,P<0.05)。在<3岁儿童中,无细胞百白破联合疫苗0-2剂次、3剂次、4剂次免疫儿童Anti-PT IgG阳性率分别为6.67%、10.75%、13.25%(χ^2=1.30,P>0.05),Anti-FHA IgG阳性率分别为6.67%、17.39%、30.12%(χ^2=6.74,P<0.05)。结论江苏省2018年健康人群Anti-PTIgG和Anti-FHAIgG水平较低;建议对特定人群进行百日咳组分疫苗选择性免疫或补充免疫。     

Assessing the reactogenicity of Tdap vaccine administered during pregnancy and antibodies to Bordetella pertussis antigens in maternal and cord sera of Thai women

IntroductionPregnant Thai women have low antibody titers against B. pertussis antigens, which coincide with an increasing incidence of pertussis among Thai infants. Thus, there exists a potential benefit of a booster dose of tetanus- diphtheria-acellular pertussis (Tdap) vaccine administered during pregnancy. Here, we report the vaccine reactogenicity profile and birth outcomes in Tdap-vaccinated pregnant women who have or have not had prior immunization with tetanus vaccine, and the IgG levels to B. pertussis antigens in maternal and cord sera at delivery.Materials and methodsPregnant women (N = 370) aged 18–40 years were administered the Tdap vaccine (Boostrix®, GlaxoSmithKline, Rixensart, Belgium) at 26–36 weeks gestation. Adverse events following vaccination were identified by follow-up telephone call and medical record review. IgG against pertussis toxin (anti-PT), filamentous hemagglutinin (anti-FHA) and pertactin (anti-PRN) in both maternal and umbilical cord blood obtained at delivery were quantitatively evaluated using enzyme-linked immunosorbent assay (EUROIMMUN®, Lübeck, Germany).ResultsThere was no reported increase in the severity or duration of adverse events associated with the administration of an extra tetanus-containing vaccine within the previous five years (N = 181) or multiple doses of tetanus-containing vaccines during the current pregnancy (N = 98). Vaccination at least eight weeks prior to delivery resulted in high antibody titers to all B. pertussis antigens studied.ConclusionsThe reactogenicity of Tdap vaccine administered during pregnancy was not affected by prior tetanus toxoid immunization. High transplacental antibody against B. pertussis antigens in the cord blood provides evidence of antibody transfer and should thus help to protect newborns from pertussis during early life.     

Pertussis vaccination during pregnancy: Antibody persistence in infants

Maternal pertussis vaccination is associated with higher levels of pertussis antibodies at birth. We assessed the persistence of pertussis antibodies until primary vaccination in infants whose mothers received Tdap (tetanus, diphtheria, acellular pertussis) vaccine during pregnancy. Infants were born at the Hospital Clinic of Barcelona (Spain) in November 2014. Anti-PT IgG was determined by ELISA at delivery, between the first and second month of life, and estimated at 2 months of age. The study included 37 infants whose mothers received Tdap between 21 and 38 weeks of gestation. Infants presented a decline in GMC of anti-PT IgG between peripartum and follow-up levels, 52.7 (95% CI 34.7–80.2) versus 7.5 (95% CI 4.2–13.3) at 2 months of age (p < 0.001). The median half-life of maternal antibodies was 47 days. More than half (51.4%) the infants presented detectable anti-PT IgG before the start of primary infant vaccination.     

Estimated and reported incidence of pertussis in Estonian adults: A seroepidemiological study

ObjectivesRates of pertussis immunisation among children in Estonia are high (∼95%), but pertussis is still the most common vaccine preventable childhood disease. Adults are suspected to be sources of pertussis in children. We aimed to measure pertussis toxin (PT) IgG in adults to estimate pertussis infection activity and compare estimated and reported pertussis incidences.MethodsIn a cross-sectional serosurvey, consecutive leftover blood sera (n = 3327) from subjects aged 20–99 years old were collected at Quattromed HTI laboratories between the 7th January and 27th February 2013. Anti-PT IgG concentration was measured by ELISA (Euroimmun, Lübeck, Germany). Estimated annual pertussis incidence was calculated for 10-year age classes using de Melker et al. (2006. J Infect. 53(2):106–13) formula.ResultsThe mean number of samples in each 10-year age class was 466 (SD 20.5), except for 90–99 year olds which contained 65 samples.More than half of all subjects (58.1%) had anti-PT IgG <5.0 IU/mL, 2.7% had 62.5 to <125 IU/mL and 0.6% ≥125 IU/mL; no differences occurred between 10-year age classes.Estimated incidence of pertussis infection was 5.8% (95% CI 4.8–7.0) in 2012, with peaks observed in 20–29 year olds (11.0%; 95% CI 7.4–15.6) and 90–99 year olds (10.8%; 95% CI 3.0–26.2). Estimated pertussis incidence rate was 915 times higher than reported.Of 80 subjects with anti-PT IgG ≥62.5 IU/mL, 25 (31.3%) had complained of coughing to their GP during the previous six months.ConclusionThe frequency of pertussis infection was similar for all ages, suggesting similar Bordetella pertussis activity in adults and children. The wide gap between reported and estimated incidence indicates poor recognition of pertussis, likely owing to it being an asymptomatic or mild disease.     

Distribution of pertussis antibodies among different age groups in Japan

We examined the distribution of antibody levels against pertussis toxin (PT) and filamentous hemagglutinin (FHA) among a healthy Japanese population aged from 0 to 77 years. Levels of both antibodies in 1108 serum samples collected in 1994 from nine prefectures were assayed using polystyrene ball ELISA. The ratio of individuals positive (>or=10 ELISA U/ml) for anti-PT and anti-FHA antibodies at ages ranging from 0 to 3 years increased rapidly with the increase in the population vaccinated over three times with acellular pertussis (aP) vaccine. However, the ratio of those positive for anti-PT antibody tended to decrease until 6-8 years of age and to increase again from 9 to 19 years among the vaccinated population, although the ratio of individuals positive for anti-FHA antibody remained constant at 80-100% in children and adolescents over 3 years old. Moreover, positivity for anti-PT antibody was high (>or=50 ELISA U/ml) in some serum samples collected from adolescents and young adults, suggesting recent symptomatic or asymptomatic infection with circulating Bordetella pertussis. On the other hand, 50-60% of infants below 12 months of age was below the detection limit (1.0 ELISA U/ml) for anti-PT and anti-FHA antibodies, and most early infants were not vaccinated for pertussis. Since intermittent circulation of B. pertussis remains among the Japanese population, complete vaccination with aP vaccine for all infants should be highly recommended to prevent pertussis.