Vaccine preventable bacterial diseases in Belgium: monitoring of general population immunity and pregnancy vaccination strategies

&lt;p&gt;Diphtheria, tetanus and pertussis are three serious infectious diseases caused by bacteria and that can be prevented by vaccination. Diphtheria and tetanus are now under control although sporadic cases still occur in highly vaccinated populations, whereas pertussis is re-emerging in some developed countries despite the high vaccination coverage. In this thesis, we have monitored the population immunity level in Belgium in different age groups and studied the immune responses in the context of pregnancy vaccination strategies against diphtheria, tetanus and pertussis. A pentaplex immunoassay was developed for simultaneous detection of IgG antibodies induced by five vaccine antigens i.e. DT, TT, PT, FHA and Prn. We identified an underprotective antibody level against diphtheria and tetanus and confirmed the circulation of B. pertussis among the Belgian adult population. Tdap vaccination during pregnancy induced sustained humoral and transient cellular response in women to the same extent in pregnant and nonpregnant women. High maternal antibodies were efficiently transferred through the placenta closing the susceptibility gap in infants prior to their first DTaP vaccination. All infants showed good antibody responses to the vaccine albeit minor inhibition by residual maternal antibodies was observed for infant antibodies to PT in terms of quantity and quality. Our results indicated that efforts should be made to improve the vaccination status of the adult population, particularly for diphtheria. They also support the recommendation of pregnancy vaccination strategies. The clinical significance of maternal antibodies interference on infant immune response should be further investigated.&lt;/p&gt;</p

A Belgian Serosurveillance/Seroprevalence Study of Diphtheria, Tetanus and Pertussis Using a Luminex xMAP Technology-Based Pentaplex

&lt;p&gt;Serosurveillance and seroprevalence studies are an essential tool to monitor vaccine-preventable diseases. We have developed a magnetic bead-based pentaplex immunoassay (MIA) for the simultaneous detection of IgG antibodies against diphtheria toxin (DT), tetanus toxin (TT), pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (Prn). The in-house pentaplex MIA showed a good correlation with commercial ELISAs with correlation coefficients between 0.89 for PT and 0.98 for TT. Intra- and inter-assay variability was &amp;lt;10%. A total of 670 anonymized serum samples collected in 2012 in Belgian adults (ages 20-29.9 years) were analyzed. Geometric mean concentrations (GMC) were 0.2 (0.13-0.29) IU/mL for DT, 0.63 (0.45-0.82) IU/mL for TT, 3.9 (2.6-5.8) IU/mL for PT, 16.3 (11.7-22.7) IU/mL for FHA and 15.4 (10.1-23.6) IU/mL for Prn. Antibody concentrations were below the protective level of 0.1 IU/mL in 26.4% of the sera for DT and in 8.6% of the sera for TT. Anti-PT IgG concentrations indicative of recent pertussis infection (&amp;gt;125 IU/mL) were detected in 1.2% of the subjects. High anti-PT antibodies were not correlated with high antibodies against any of the four other vaccine antigens. This pentaplex MIA will be used for a new large-scale Belgian serosurveillance/seroprevalence study of diphtheria, tetanus and pertussis.&lt;/p&gt;</p

The performance of multiplex immunoassays for antibody determination to diphtheria, tetanus and pertussis: a need for standardisation

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

&lt;p&gt;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.&lt;/p&gt;</p

Pertussis vaccination during pregnancy in Belgium: Results of a prospective controlled cohort study.

&lt;p&gt;Vaccination during pregnancy has been recommended in some countries as a means to protect young infants from severe infection. Nevertheless, many aspects are still unknown and possible blunting of the infant&amp;#39;s immune responses by maternal antibodies, is one of the concerns with maternal vaccination. We report the first prospective controlled cohort study in women and infants on the effects of using Boostrix(&amp;reg;), a combined tetanus, diphtheria and acellular pertussis vaccine, during pregnancy. The primary aim was to measure the influence of this booster dose on the titer and duration of the presence of maternal antibodies in the infants and assess possible interference with infant immune responses. In a controlled cohort study, 57 pregnant women were vaccinated with Tdap vaccine (Tetanus Diphtheria acellular Pertussis, Boostrix, GSK Biologicals), at a mean gestational age of 28.6 weeks. A control group of pregnant women (N=42) received no vaccine. Antibody geometric mean concentrations (GMCs) against tetanus (TT), diphtheria (DT), pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (Prn) were measured with commercial ELISA tests in samples taken preceding maternal vaccination and one month afterwards, at delivery and from the cord blood, and in infants before and 1 month after the primary series of 3 pertussis containing hexavalent vaccines. Infants born to vaccinated women had significantly higher GMC at birth and during the first 2 months of life for all vaccine antigens compared to the offspring of unvaccinated women, thereby closing the susceptibility gap for pertussis in infants. However, blunting was noticed for infant diphtheria and pertussis toxin vaccine responses (p&amp;lt;0.001) in the infants from vaccinated women after the primary vaccination schedule (weeks 8,12 and 16). Since pertussis vaccination has been recommended during pregnancy already, the results of this study support that recommendation and provide additional scientific evidence to document possible interference by maternal antibodies.&lt;/p&gt;</p

Influence of maternal vaccination against diphtheria, tetanus, and pertussis on the avidity of infant antibody responses to a pertussis containing vaccine in Belgium.

&lt;p&gt;Maternal antibodies induced by vaccination during pregnancy cross the placental barrier and can close the susceptibility gap to pertussis in young infants up to the start of primary immunization. As not only the quantity but also the quality of circulating antibodies is important for protection, we assessed whether maternal immunization affects the avidity of infant vaccine-induced IgG antibodies, in the frame of a prospective clinical trial on pregnancy vaccination in Belgium. Infants born from Tdap (Boostrix®) vaccinated (N = 55) and unvaccinated (N = 26) mothers were immunized with a hexavalent pertussis containing vaccine (Infanrix Hexa®) at 8, 12 and 16 weeks, followed by a fourth dose at 15 months of age. Right before and one month after this fourth vaccine dose, the avidity of IgG antibodies against diphtheria toxin (DT), tetanus toxin (TT), pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (Prn) was determined using 1.5 M ammonium thiocyanate as dissociating agent. In both groups, antibody avidity was moderate for TT, PT, FHA and Prn and low for DT after priming. After a fourth dose, antibody avidity increased significantly to high avidity for TT and PT, whereas it remained moderate for FHA and Prn and low for DT. The avidity correlated positively with antibody level in both study groups, yet not significantly for PT. When comparing both study groups, only PT-specific antibodies showed significantly lower avidity in infants born from vaccinated than from unvaccinated mothers after the fourth vaccine dose. The clinical significance of lower avidity of vaccine induced infant antibodies after maternal vaccination, if any, needs further investigation.&lt;/p&gt;</p

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

&lt;p&gt;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(&amp;reg;)) during pregnancy (vaccine group) or received no vaccine (control group). All infants were vaccinated with Infanrix Hexa(&amp;reg;) 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.&lt;/p&gt;</p