Distinct T-cell subtypes induced with whole cell and acellular pertussis vaccines in children.

Recent clinical trials have demonstrated that new generation acellular pertussis vaccines can confer protection against whooping cough. However, the mechanism of protective immunity against Bordetella pertussis infection induced by vaccination remains to be defined. We have examined cellular immune responses in children immunized with a range of acellular and whole cell pertussis vaccines. Immunization of children with a potent whole-cell vaccine induced B. pertussis-specific T cells that secreted interferon-gamma (IFN-gamma), but not interleukin-5 (IL-5). In contrast, T cells from children immunized with acellular pertussis vaccines secreted IFN-gamma and/or IL-5 following stimulation with B. pertussis antigens in vitro. These observations suggest that protective immunity conferred by whole-cell vaccines, like natural immunity, is mediated by type 1 T cells, whereas the mechanism of immune protection generated with acellular vaccines may be more heterogeneous, involving T cells that secreted type 1 and type 2 cytokines.     

Long-term pertussis-specific immunity after primary vaccination with a combined diphtheria, tetanus, tricomponent acellular pertussis, and hepatitis B vaccine in comparison with that after natural infection

The aim of this study was to compare pertussis-specific humoral and cellular immunity in children 5 years after a primary vaccination with a combined diphtheria, tetanus, tricomponent acellular pertussis, and hepatitis B vaccine (DTaP-HBV; InfanrixHepB; SmithKline Beecham) with immunity after natural infection. The subjects were 38 children aged 5 to 6 years who received DTaP-HBV at 3, 5, and 11 months of life and 21 subjects of similar ages and sex who acquired pertussis in the first year of life. Immunoglobulin G (IgG) antibody titers against Bordetella pertussis antigens, peripheral blood mononuclear cell-specific proliferation, and the secretion of cytokines were evaluated. After 5 years, only a small proportion of vaccinated and infected children had significant specific concentrations of IgG in serum against all three B. pertussis antigens, and T-cell responses persisted in a minority of subjects. A preferential type 1 cytokine response with the secretion of gamma interferon was observed in the pertussis group, whereas a type 2 skewed response was observed in the vaccinated children; however, the quantitative differences in the cytokines produced by DTaP-HBV and natural infection were minimal. In conclusion, our results show that the immune responses induced by primary pertussis vaccination are qualitatively and quantitatively similar to those seen in children who recovered from natural infection and highlight the need for booster immunization with pertussis vaccines in order to maintain adequate levels of a specific immune response to B. pertussis.     

Seroprevalence of IgG antibodies against Bordetella pertussis in healthy individuals aged 4–24 years in Turkey

The distribution of IgG antibodies to Bordetella pertussis was investigated in serum samples from 550 subjects, aged 4–24 years, to determine the optimal age for booster immunisation. Levels of antibody to B. pertussis antigens were determined using an ELISA that measures a mixture of pertussis toxin, filamentous haemagglutinin and lipopolysaccharide. Geometric mean titres of anti-pertussis antibodies in subjects aged 4–6 years were significantly lower than those in other age groups, which reflects waning immunity following vaccination. High positive titres in older children and adolescents suggested acquired B. pertussis infection, and booster doses at the ages of 7 and 15 years are therefore suggested.     

Haemophilus influenzae type b and pertussis vaccinations in preterm infants

Introduction: The aim of the study was to evaluate the serological efficacy of Hiberix and Infanrix-DTPa vaccines in preterm infants. Materials and Methods: The results of the investigation of 61 preterm infants immunized three times (primary vaccination) with Hiberix and Infanrix-DTPa at 6-week intervals are presented. Of the 61 children, 17 were additionally immunized with a booster dose of these vaccines. Postvaccinal response to these immunizations was evaluated by means of an immunoenzymatic method. Results: We observed a significant increase in protective postvaccinal antibody titers against Haemophilus influenzae type b (Hib) and Bordetella pertussis after the primary vaccination compared with the initial antibody levels (p<0.05). A significant increase (p<0.0002) in protective antibody titers after the booster dose of Hiberix compared with the primary vaccination was also noted. No correlations between birth weight, gestational age, and the achieved levels of postvaccinal anti-polyribosylribitol phosphate of Hib and of anti-pertussis toxin and anti-filamentous hemagglutinin of B. pertussis antibodies after the primary vaccination or booster dose were found. After the booster dose, all the preterm infants responded with the production of protective postvaccinal antibody titers against Hib and B. pertussis. Conclusions:Due to the very good immunogenicity of the vaccines against Hib studied, inclusion of this immunization should be proposed in the obligatory vaccination schedule in Poland, especially in preterm infants. An additional immunization (i.e. a second booster dose) of Polish children with acellular pertussis (DTPa) vaccine is necessary to protect them from decreasing protective anti-pertussis antibody titers in early childhood.     

T-Cell Responses before and after the Fifth Consecutive Acellular Pertussis Vaccination in 4-Year-Old Dutch Children

Immunization with acellular pertussis vaccine (aP) induces higher specific antibody levels and fewer adverse reactions than does immunization with the whole-cell vaccine (wP). However, antibody levels in infants induced by both types of pertussis vaccines wane already after 1 year. Therefore, long-term T-cell responses upon vaccination might play a role in protection against pertussis. In a cross-sectional study (ISRCTN65428640), we investigated T-helper (Th) cell immune responses in wP- or aP-vaccinated children before and after an aP low-dose or high-dose preschool booster at 4 years of age in The Netherlands. T cells were stimulated with pertussis vaccine antigens. The numbers of gamma interferon-producing cells and Th1, Th2, Th17, and interleukin-10 (IL-10) cytokine concentrations were determined. In addition, pertussis-specific IgE levels were measured in plasma. Children being vaccinated with aP vaccinations at 2, 3, 4, and 11 months of age still showed higher pertussis-specific T-cell responses at 4 years of age than did wP-vaccinated children. These T-cell responses failed to show a typical increase in cytokine production after a fifth aP vaccination but remained high after a low-dose booster and seemed to decline even after a high-dose booster. Importantly, elevated IgE levels were induced after this booster vaccination. In contrast, wP-vaccinated children had only low prebooster T-cell responses, and these children showed a clear postbooster T-cell memory response even after a low-dose booster vaccine. Four high-dose aP vaccinations in infancy induce high T-cell responses still present even 3 years after vaccination and enhanced IgE responses after preschool booster vaccination. Therefore, studies of changes in vaccine dosage, timing of pertussis (booster) vaccinations, and the possible association with local side effects are necessary.     

Pertussis IgE and atopic disease

Background Pertussis toxin (PT) stimulates IgE production in animals, and pertussis vaccination and whooping cough may have similar effects in man. Methods We analyzed IgE responses to PT (FT-IgE) in sera from children primarily immunized with three doses of either an acellular 2- or 5-component vaccine, or a whole-cell (We) pertussis vaccine, and in children after whooping cough. The study comprised 50 children with both atopic disease and positive skin prick test, 99 nonatopic controls, and 40 children with verified pertussis.
Results Immunoglobulin E antibodies against PT were demonstrated in 19% and 24% of sera from vaccinated children at 7 and 12 months, respectively, and in 9% at 2.5 years. At 7 months, PT-IgE was more common after vaccination with acellular (24%) than with the We vaccine (3%, P = 0,02), PT-IgE was also more common (P = 0.00l) after vaccination in children classified as atopic (36%) than in the control group (10%). Thirty percent of the children with pertussis had PT-IgE, more often so in atopic than nonatopic children (P = 0.02), Conciusions Transient production of PT-lgE seems to be common after primary pertussis immunization with acellular vaccines, and after whooping cough, particularly in atopic subjects.     

Acellular pertussis vaccine protects against exacerbation of allergic asthma due to Bordetella pertussis in a murine model

The prevalence of asthma and allergic disease has increased in many countries, and there has been speculation that immunization promotes allergic sensitization. Bordetella pertussis infection exacerbates allergic asthmatic responses. We investigated whether acellular pertussis vaccine (Pa) enhanced or prevented B. pertussis-induced exacerbation of allergic asthma. Groups of mice were immunized with Pa, infected with B. pertussis, and/or sensitized to ovalbumin. Immunological, pathological, and physiological changes were measured to assess the impact of immunization on immune deviation and airway function. We demonstrate that immunization did not enhance ovalbumin-specific serum immunoglobulin E production. Histopathological examination revealed that immunization reduced the severity of airway pathology associated with sensitization in the context of infection and decreased bronchial hyperreactivity upon methacholine exposure of infected and sensitized mice. These data demonstrate unequivocally the benefit of Pa immunization to health and justify selection of Pa in mass vaccination protocols. In the absence of infection, the Pa used in this study enhanced the interleukin-10 (IL-10) and IL-13 responses and influenced airway hyperresponsiveness to sensitizing antigen; however, these data do not suggest that Pa contributes to childhood asthma overall. On the contrary, wild-type virulent B. pertussis is still circulating in most countries, and our data suggest that the major influence of Pa is to protect against the powerful exacerbation of asthma-like pathology induced by B. pertussis.     

Whole-cell pertussis vaccine protects against Bordetella pertussis exacerbation of allergic asthma

The prevalence of asthma and allergic disease has increased in many countries and there has been speculation that immunization promotes allergic sensitization. Bordetella pertussis infection exacerbates allergic asthmatic responses. We investigated whether whole-cell pertussis vaccine (Pw) enhanced or prevented B. pertussis induced exacerbation of allergic asthma. Groups of mice were immunized with Pw, infected with B. pertussis and/or sensitized to ovalbumin. Immunological, pathological and physiological changes were measured to assess the impact of Pw immunization on immune deviation and airway function. Pw immunization modulated ovalbumin-specific serum IgE production, and reduced local and systemic IL-13 and other cytokine responses to sensitizing allergen. Histopathological examination revealed Pw immunization reduced the severity of airway pathology and decreased bronchial hyperreactivity to methacholine exposure. Pw does not enhance airway IL-13 and consequently does not enhance but protects against the exacerbation of allergic responses. We find no evidence of Pw contributing to allergic asthma, but rather provide evidence of a mechanism whereby whole-cell pertussis vaccination has a protective role.     

Recombinant Mycobacterium bovis BCG expressing pertussis toxin subunit S1 induces protection against an intracerebral challenge with live Bordetella pertussis in mice

The recent development of acellular pertussis vaccines has been a significant improvement in the conventional whole-cell diphtheria-pertussis-tetanus toxoid vaccines, but high production costs will limit its widespread use in developing countries. Since Mycobacterium bovis BCG vaccination against tuberculosis is used in most developing countries, a recombinant BCG-pertussis vaccine could be a more viable alternative. We have constructed recombinant BCG (rBCG) strains expressing the genetically detoxified S1 subunit of pertussis toxin 9K/129G (S1PT) in fusion with either the beta-lactamase signal sequence or the whole beta-lactamase protein, under control of the upregulated M. fortuitum beta-lactamase promoter, pBlaF*. Expression levels were higher in the fusion with the whole beta-lactamase protein, and both were localized to the mycobacterial cell wall. The expression vectors were relatively stable in vivo, since at two months 85% of the BCG recovered from the spleens of vaccinated mice maintained kanamycin resistance. Spleen cells from rBCG-S1PT-vaccinated mice showed elevated gamma interferon (IFN-gamma) and low interleukin-4 (IL-4) production, as well as increased proliferation, upon pertussis toxin (PT) stimulation, characterizing a strong antigen-specific Th1-dominant cellular response. The rBCG-S1PT strains induced a low humoral response against PT after 2 months. Mice immunized with rBCG-S1PT strains displayed high-level protection against an intracerebral challenge with live Bordetella pertussis, which correlated with the induction of a PT-specific cellular immune response, reinforcing the importance of cell-mediated immunity in the protection against B. pertussis infection. Our results suggest that rBCG-expressing pertussis antigens could constitute an effective, low-cost combined vaccine against tuberculosis and pertussis.     

A live, attenuated Bordetella pertussis vaccine provides long-term protection against virulent challenge in a murine model

Despite successful mass vaccination programs, whooping cough remains a significant cause of neonatal mortality. Immunity induced by current vaccines wanes in adolescence, requiring additional immunizations to prevent resurgence. There is a need for a new generation of vaccines capable of conferring long-lasting immunity from birth. Recently, a live, attenuated whooping cough vaccine, BPZE1, has been developed. Here, an established murine immunization model was used to examine the induction and longevity of immunological memory. In this predictive model, BPZE1 conferred a level of protection against virulent bacterial challenge comparable to that conferred by recovery from prior infection, up to 1 year after immunization. One year after immunization with BPZE1, a pertussis-specific persistent response, with high levels of gamma interferon (IFN-γ), could be detected from spleen cells restimulated with inactivated Bordetella pertussis. BPZE1 induced low levels of interleukin-17 (IL-17) and no IL-10 or IL-5. BPZE1 immunization induced long-lasting, efficacious memory B-cell and specific antibody responses dominated by IgG2a, which were boosted by subsequent challenge. Finally, the antibody induced by BPZE1 was functionally relevant and could clear a virulent B. pertussis infection in antibody-deficient mice following passive transfer. This study suggests that BPZE1 is capable of conferring a high level of long-lived effective protection against virulent B. pertussis.     

Pertussis booster vaccination and immediate hypersensitivity

Twelve non-atopic and 27 atopic preschool children were studied to determine the effect of pertussis booster vaccination on cutaneous histamine sensitivity and IgE antibody response to the naturally-occurring ragweed aeroallergen. Prick tests of histamine and ragweed extract, as well as ragweed-RAST, were performed prior to, and after, their booster injections. Ragweed skin tests and RAST were not repeated until 2 weeks after the end of ragweed pollination. None of the parameters changed significantly in either group regardless of the type of immunization administered.     

A Murine Model in Which Protection Correlates with Pertussis Vaccine Efficacy in Children Reveals Complementary Roles for Humoral and Cell-Mediated Immunity in Protection against Bordetella pertussis

The results of phase 3 efficacy trials have shown that acellular and whole-cell pertussis vaccines can confer protection against whooping cough. However, despite the advances in vaccine development, clinical trials have not provided significant new information on the mechanism of protective immunity against Bordetella pertussis. Classical approaches based on measurement of antibody responses to individual antigens failed to define an immunological correlate of protection. A reliable animal model, predictive of acellular and whole-cell pertussis vaccine potency in children, would facilitate an elucidation of the mechanism of immune protection against B. pertussis and would assist in the regulatory control and future development of pertussis vaccines. In this study, we have shown that the rate of B. pertussis clearance following respiratory challenge of immunized mice correlated with vaccine efficacy in children. Using this model together with mice with targeted disruptions of the gamma interferon (IFN-γ) receptor, interleukin-4 or immunoglobulin heavy-chain genes, we have demonstrated an absolute requirement for B cells or their products in bacterial clearance and a role for IFN-γ in immunity generated by previous infection or immunization with the whole-cell pertussis vaccine. The results of passive immunization experiments suggested that protection early after immunization with acellular pertussis vaccines is mediated by antibody against multiple protective antigens. In contrast, more complete protection conferred by previous infection or immunization with whole-cell pertussis vaccines reflected the induction of Th1 cells. Our findings suggest that the mechanism of immunity against B. pertussis involves humoral and cellular immune responses which are not directed against a single protective antigen and thus provide an explanation for previous failures to define an immunological correlate of protection.     

Fasciola hepatica Suppresses a Protective Th1 Response against Bordetella pertussis

Fasciolosis, like other helminth infections, is associated with the induction of T-cell responses polarized to the Th2 subtype. Respiratory infection with Bordetella pertussis or immunization with a pertussis whole-cell vaccine (Pw) induces a potent Th1 response, which confers a high level of protection against bacterial challenge. We have used these two pathogens to examine bystander cross-regulation of Th1 and Th2 cells in vivo and provide evidence of immunomodulation of host T-cell responses to B. pertussis by a concomitant infection with Fasciola hepatica. Mice with a coinfection of F. hepatica and B. pertussis exhibited a Th2 cytokine profile in response to F. hepatica antigens, similar to those infected with F. hepatica alone. By contrast, the Th1 response to B. pertussis antigens was markedly suppressed and the bacterial infection was exacerbated following infection with F. hepatica. Furthermore, an established Th1 response induced in mice by infection with B. pertussis or by parenteral immunization with Pw was also suppressed following infection with F. hepatica. This immunomodulatory effect of B. pertussis-induced responses by F. hepatica infection is significantly reduced, but not completely abrogated, in IL-4 knockout mice. Our findings demonstrate that Th2-inducing parasites can exert bystander suppression of protective Th1 responses to infection or vaccination with a bacterial pathogen and that the modulation is mediated in part by IL-4 and, significantly, is effective at both the induction and effector stages of the Th1 response.     

Maternal immunity provides protection against pertussis in newborn piglets

Pertussis continues to be a significant cause of morbidity and mortality in infants and young children worldwide. Methods to control the disease are based on vaccination with either whole-cell or acellular vaccines or treatment with antibiotics. However, despite worldwide vaccination infants are still at the highest risk for the disease. Here we used our newly developed newborn-piglet model to investigate whether transfer of maternal immunity can protect newborn piglets against infection with Bordetella pertussis. Pregnant sows were vaccinated with heat-inactivated B. pertussis or treated with saline (controls). Newborn piglets were allowed to suckle colostrum and milk for 4 to 5 days before they were challenged with 5 x 10(9) CFU of bacteria intrapulmonarily. Elevated levels of B. pertussis-specific secretory immunoglobulin A (S-IgA) and IgG antibodies were found in the colostrum and serum of vaccinated sows but not in those of control sows. Subsequently, significant levels of specific IgG and S-IgA were detected in the serum and bronchoalveolar lavage fluid of piglets born to vaccinated sows. Following infection with 5 x 10(9) CFU of B. pertussis, clinical symptoms, pathological alterations, and bacterial shedding were significantly reduced in piglets that had received passively transferred immunity. Thus, our results demonstrate that maternal immunization might represent an alternative approach to provide protection against pertussis in young infants.     

Changes of the Swedish Bordetella pertussis population in incidence peaks during an acellular pertussis vaccine period between 1997 and 2004

In a surveillance programme undertaken from 1997 through 2004, Bordetella pertussis isolates and clinical information were collected after introduction of acellular pertussis vaccines (Pa) in 1996. Changes in the B. pertussis population were studied in three incidence peaks: 1999-2000, 2002 and 2004. Available isolates from 158 fully vaccinated children representing all of Sweden, plus 37 from the Gothenburg area 2003-2004, were analysed by pulsed-field gel electrophoresis (PFGE), serotyping and sequencing of the virulence factor genes pertussis toxin subunits 1 and 3 (ptxA, ptxC), pertactin (prn), tracheal colonisation factor (tcfA) and fimbria3 (fim3). Allele ptxA1 was found in all isolates. There was a statistically significant increasing trend in three out of five studied genes, ptxC, prn and tcfA, and for a fourth, Fim3, if Gothenburg strains were included. The PFGE profile BpSR11 appearing in the 1999-2000 peak dominated by >or=23% during the entire period, bringing with it the allele combination 1/2/2/2/B (ptxA1/ptxC2/prn2/tcfA2/fim3B). Other BpSR11-related profiles with the same allele combination and more than 82% similarity--BpSR5 in the 2002 peak and BpSR12 in the 2004 peak--appeared with an increasing trend. Although vaccination with Pa has reduced disease, new variants have emerged representing clones surviving in the immunized population.     

Acellular pertussis vaccines and the role of pertactin and fimbriae

The introduction of acellular pertussis (Pa) vaccines in countries with a low uptake of whole-cell pertussis (Pw) vaccines has led to a dramatic reduction in pertussis disease. Diphtheria-tetanus-acellular pertussis (DTPa) vaccines have also ensured continued high level disease protection in these countries following the shift from Pw- to Pa-containing vaccines, and allowed pertussis booster programs to be implemented. Vaccines containing between one and five components have been licensed and implemented. Those with three or more components consisting of filamentous hemagglutinin (FHA), pertussis toxin (PT) and pertactin (PRN) are considered to be more effective than one/two-component Pa vaccines that contain only PT or both PT and FHA. Changes in circulating Bordetella pertussis strains may impact vaccine efficacy and, thus, incidence and transmission of pertussis and deserve to be followed carefully. To date, vaccine-induced shifts among fimbriae (FIM) are reported and this could impact the efficacy of FIM-containing vaccines. Currently, FIM3 appears to be dominant in most European countries, Canada and Australia. Data obtained from a DTPa5 vaccine containing FIM2 and FIM3 have indicated a shift towards an increase in FIM3-expressing B. pertussis clinical breakthrough cases when compared with control vaccine. By contrast, relatively minor PT and PRN sequence polymorphisms have been identified without demonstrable association with vaccination programs. Adsorption of PRN to aluminum salt appears critical for optimal protective capacity in murine pertussis lung challenge. In addition, clinical studies have shown anti-PRN antibody levels to be higher when PRN is adsorbed at a 8-microg dosage versus non-adsorbed PRN at a 3-microg dosage. The available data, therefore, demonstrate that appropriately formulated acellular vaccines containing PT and PRN are the preferred option for pertussis immunization.     

Seroprevalence of IgG antibodies against Bordetella pertussis in healthy individuals aged 4-24 years in Turkey.

The distribution of IgG antibodies to Bordetella pertussis was investigated in serum samples from 550 subjects, aged 4-24 years, to determine the optimal age for booster immunisation. Levels of antibody to B. pertussis antigens were determined using an ELISA that measures a mixture of pertussis toxin, filamentous haemagglutinin and lipopolysaccharide. Geometric mean titres of anti-pertussis antibodies in subjects aged 4-6 years were significantly lower than those in other age groups, which reflects waning immunity following vaccination. High positive titres in older children and adolescents suggested acquired B. pertussis infection, and booster doses at the ages of 7 and 15 years are therefore suggested.     

A regulatory role for interleukin 4 in differential inflammatory responses in the lung following infection of mice primed with Th1- or Th2-inducing pertussis vaccines

Protection against infectious pathogens at mucosal surfaces is dependent on local antibody responses, production of inflammatory mediators, and recruitment of immune effector cells to the site of infection. Since Th1 and Th2 cells produce cytokines with pro- and anti-inflammatory activities, immunization with vaccines that induce these T-cell subtypes may regulate the subsequent inflammatory response to infection. We have demonstrated that immunization of mice with pertussis whole-cell or acellular vaccines (Pw or Pa) selectively induces Th1 and Th2 cells, respectively. In this study we have used a murine respiratory-infection model to demonstrate that priming with a Th1- or Th2-inducing pertussis vaccine can influence the local inflammatory response and immune effector cells in the lung following aerosol challenge with Bordetella pertussis. Analysis of bronchoalveolar lavage (BAL) fluid taken during the course of B. pertussis infection of na?ve mice or mice immunized with Pw revealed an early influx of neutrophils and local production of interleukin 1beta (IL-1beta) in the lungs. In contrast, neutrophil infiltration and IL-1beta production were not observed following challenge of mice immunized with the Th2-inducing Pa. Conversely, during infection local production of IL-6 and IL-1ra was significantly greater in mice immunized with Pa than in those immunized with Pw. Studies of knockout mice revealed neutrophil and lymphocyte infiltration in the lungs following B. pertussis infection of IL-4-defective (IL-4(-/-)) mice but not in wild-type mice immunized with Pa. Furthermore, the levels of IL-1beta, IL-6, and IL-1ra in Pa-immunized IL-4(-/-) mice were comparable to those in mice immunized with Pw. These results demonstrate distinct influences of Th1- and Th2-inducing vaccines on the protective inflammatory responses in the lungs following challenge with B. pertussis and implicate IL-4 as an important regulator of inflammatory-cell recruitment.     

Immune Responses to Pertussis Antigens in Infants and Toddlers after Immunization with Multicomponent Acellular Pertussis Vaccine

Given the resurgence of pertussis despite high rates of vaccination with the diphtheria-tetanus-acellular pertussis (DTaP) vaccine, a better understanding of vaccine-induced immune responses to Bordetella pertussis is needed. We investigated the antibody, cell-mediated, and cytokine responses to B. pertussis antigens in children who received the primary vaccination series (at 2, 4, and 6 months) and first booster vaccination (at 15 to 18 months) with 5-component acellular pertussis (aP) vaccine. The majority of subjects demonstrated a 4-fold increase in antibody titer to all four pertussis antigens (pertussis toxin [PT], pertactin [PRN], filamentous hemagglutinin [FHA], and fimbriae [FIM]) following the primary series and booster vaccination. Following the primary vaccine series, the majority of subjects (52 to 67%) mounted a positive T cell proliferative response (stimulation index of ≥3) to the PT and PRN antigens, while few subjects (7 to 12%) mounted positive proliferative responses to FHA and FIM. One month after booster vaccination (age 16 to 19 months), our study revealed significant increase in gamma interferon (IFN-γ) production in response to the PT and FIM antigens, a significant increase in IL-2 production with the PT, FHA, and PRN antigens, and a lack of significant interleukin-4 (IL-4) secretion with any of the antigens. While previous reports documented a mixed Th1/Th2 or Th2-skewed response to DTaP vaccine in children, our data suggest that following the first DTaP booster, children aged 16 to 19 months have a cytokine profile consistent with a Th1 response, which is known to be essential for clearance of pertussis infection. To better define aP-induced immune responses following the booster vaccine, further studies are needed to assess cytokine responses pre- and postbooster in DTaP recipients.