Efficacy and immunogenicity of acellular pertussis vaccine by manufacturer and patient age

Acellular pertussis vaccines, which have been used in Japan since 1981, vary in antigenic constituents among manufacturers. First, to assess the immunogenicity by manufacturer and patient age, 161 children aged 3 months to 2 years were immunized by acellular pertussis vaccine from one of three Japanese manufacturers, Biken, Takeda, or Kitasato. Anti-pertussis toxin antibody responses for children immunized with Takeda and Kitasato vaccines were comparable with patients with pertussis in the convalescent stage, and anti-pertussis toxin antibody response for Biken vaccine was far higher than those of convalescing patients. Anti-filamentous hemagglutinin antibody responses for the children given the three vaccines were far higher than those of the patients. Weak serotype 1.3 agglutinin responses were observed only in children administered the Takeda vaccine. Comparing these antibody responses among various age groups, the immunogenicity of acellular vaccines in children aged 3 to 6 months was comparable with children aged 2 years. Second, to assess the manufacturer-specific efficacy, 495 households of patients with pertussis were surveyed from 1981 to 1988. The estimated efficacy of the acellular pertussis vaccines in children aged 2 to 8 years was 82%, and there were no major differences in the secondary attack rates among children immunized with acellular pertussis vaccine from each manufacturer, ie, 12.5% (1/8) for Biken, 11.1% (2/18) for Takeda, and 5.9% (1/17) for Kitasato. We conclude from these two studies that similar efficacy was observed in children aged 2 years or older for acellular pertussis vaccines from the three manufacturers, which produced anti-pertussis toxin antibody responses comparable with patients with pertussis and far higher antifilamentous hemagglutinin antibody responses than in the convalescing patients, and that age did not affect the immunogenicity of acellular vaccines.     

Comparison of a fifth dose of a five-component acellular or a whole cell pertussis vaccine in children four to six years of age.

BACKGROUND AND OBJECTIVES: Acellular pertussis vaccines are now preferred for all five childhood immunization doses; however, there are few data on the safety and immunogenicity of five consecutive doses. This study compared a fifth dose of an acellular and a whole cell pertussis vaccine in 4- to 6-year-old children previously immunized with four doses of acellular or whole cell pertussis vaccine. STUDY DESIGN: In a double blind, multicenter study, 366 healthy children were randomly allocated to receive a single injection of a 5-component acellular or a whole cell pertussis vaccine, each combined with diphtheria and tetanus toxoids and inactivated poliovirus vaccine. RESULTS: Although injection site redness > or =50 mm and swelling > or =50 mm were common in children who had received five doses of acellular (50% and 48.1%, respectively) or whole cell (66.2% and 59.7%) pertussis vaccine, limb soreness and limitation of motion were less frequently reported after acellular (1.9% and 0%) than after whole cell (49.2% and 36.3%; P < 0.0001) pertussis vaccine. Pre-fifth dose antipertussis antibody titers were higher in children who previously had received four doses of acellular pertussis vaccine. Postimmunization antibody titers against pertussis toxin, filamentous hemagglutinin, pertactin and tetanus toxin were higher in recipients of five doses of acellular pertussis vaccine, whereas antibody titers to diphtheria toxin, pertussis fimbriae and poliovirus serotypes were higher in recipients of five doses of the whole cell pertussis vaccine (P < 0.05 for all comparisons). CONCLUSIONS: A regimen consisting of five doses of a five-component acellular pertussis combination vaccine is safe and immunogenic in pre-school children. Local adverse reactions are common but are less painful and activity-limiting than a regimen of five doses of a whole cell pertussis vaccine.     

Adverse reactions and antibody responses to acellular pertussis vaccine

Two types of acellular pertussis vaccine are used in Japan: the filamentous hemagglutinin (F-HA) predominant type and the pertussis toxin (PT)-F-HA type. We tested one lot of vaccine from each of three manufacturers (lots A and B, F-HA predominant type; lot C, PT-F-HA type). One hundred fifteen healthy children between the ages of 3 months and 23 months were immunized with one of the three lots of acellular pertussis vaccine to assess adverse reactions and antibody responses. The incidence of fever (temperature greater than or equal to 38 degrees C) was 2.6% for lot A, 1.2% for lot B, and 2.5% for lot C. The incidence of local reactions greater than 5 cm in diameter was 1.9% for lot A, 2.4% for lot B, and 3.3% for lot C. Thus no significant differences in adverse reaction were observed. The anti-PT antibody responses in the tested vaccines were equal to or greater than those in patients with pertussis in the convalescent stage, and the anti-F-HA antibody responses were far higher than those of convalescing patients. Lot C produced the highest anti-PT antibody, and Lot A the highest anti-F-HA antibody.     

Antibodies to pertussis antigens in pediatric health care workers

BACKGROUND: To compare the antibody concentrations against Bordetella antigens in health care workers in a pediatric hospital with those of two different populations without professional contact with children. METHODS: In a pediatric hospital 155 health care workers (135 female, 20 male), 292 male navy recruits after 3 months at sea and 146 regular blood donors (41 female, 105 male) were screened for antibodies of isotypes IgG and IgA to pertussis toxin (PT) and filamentous hemagglutinin (FHA) by enzyme-linked immunosorbent assay. RESULTS: Pediatric health care workers were positive for IgG anti-PT in 88%, for IgA anti-PT in 52%, for IgG anti-FHA in 99% and for IgA anti-FRA in 84%. Relative numbers for blood donors and recruits were 86 and 80% for IgG anti-PT, 56 and 55% for IgA anti-PT, 100 and 98% for IgG anti-FHA and 92 and 82% for IgA anti-FHA, respectively. Reverse cumulative distribution of all antibodies except for IgA anti-FHA showed no differences among the three groups; 2% of pediatric personnel, 3% of blood donors and 3% of navy recruits, respectively, had IgG anti-PT > or = 100 enzyme-linked immunosorbent assay units/ml, indicating a recent contact to Bordetella pertussis. CONCLUSION: Antibodies to B. pertussis antigens, such as IgG/IgA anti-PT and IgG/IgA anti-FHA, were similarly distributed in all three groups. Our results suggest that exposures leading to measurable immune responses to pertussis antigens in German pediatric health care workers are not significantly more frequent than in other populations without professional contacts with children.     

Adverse reactions and serologic response to a booster dose of acellular pertussis vaccine in children immunized with acellular or whole-cell vaccine as infants

Adverse reactions and antibody response to pertussis toxin, ie, antitoxin, after a booster injection of an acellular pertussis vaccine were studied in 2-year-old children. A majority (212/241) of the children had previously been immunized with either two or three doses of the acellular vaccine at the ages of 6, 7, and 8 months. The other 29/241 children had received three doses of a plain whole-cell pertussis vaccine at the same ages. In the children who received primary immunization with the acellular vaccine, two cases of more serious systemic reactions occurred in close temporal association with the booster injection. Less serious systemic reactions were few. Local reactions were more common in the children only immunized with the acellular vaccine. Large reactions (greater than 10 cm) were only seen in this group. A good antitoxin response was elicited in both groups. The geometric mean titer in the former whole-cell vaccine recipients was significantly higher than in the children who received only acellular vaccine. The study raised some questions concerning differences in reactogenicity and immune response after a booster injection of an acellular vaccine depending on the type of pertussis vaccine given to infants for the primary immunization.     

Acellular pertussis diphtheria-tetanus-pertussis vaccine containing separately purified pertussis toxoid,filamentous haemagglutinin and 69 kDa outer membrane protein as a booster in children

In two double-blind, randomized, comparative studies involving a total of 218 children, an acellular pertussis (DTPa) vaccine containing diphtheria and tetanus toxoids and pertussis components filamentous haemagglutinin (FHA), pertussis toxoid (PT), and 69 kDa outer membrane protein (69 kDa OMP) was administered as a booster to 17-month-old and 5-year-old children with a history of routine whole-cell diphtheria-tetanus-pertussis (DTPw) vaccination. The control groups in these studies received DTPw vaccine. Among 17-month-old toddlers, significantly lower proportions of DTPa vaccine recipients had local pain (7.3%), redness (14.5%) and swelling (9.1%) than DTPw vaccine recipients (23.6%, 30.9% and 23.6%, respectively). A trend toward fewer local reactions was also seen in 5-year-old children vaccinated with DTPa in private practice and public clinics although differences were not statistically significant. Fever (rectal temperature 38°C) was reported more frequently for DTPw vaccine recipients in both age groups. White no differences existed between groups in terms of geometric mean antibody titres (GMTs) prior to booster vaccination, anti-PT antibody GMTs were higher among DTPa vaccine recipients than among DTPw vaccine recipients after booster vaccination. The difference was statistically significant in 5-year-old subjects. Furthermore, significantly higher anti-FHA and anti-69 kDa OMP GMTs were seen in DTPa vaccine recipients in both age groups. In pre-vaccination seropositive subjects and in pre-vaccination seronegative subjects the rate of immune response to pertussis antigens was higher for DTPa than for DTPw vaccine recipients with the exception of the rate of response induced to 69 kDa OMP in 5-year-old children. The lower frequency of side-effects and similar or greater immunogenicity of DTPa vaccine when used as a booster in subjects primed with DTPw encourage the introduction of this type of vaccine for the fourth and fifth DTP doses that are routinely administered in many countries.     

Immunogenicity and reactogenicity of Takeda acellular pertussis-component diphtheria-tetanus-pertussis vaccine in 2- and 3-month-old children in Japan.

OBJECTIVE--To compare the reactogenicity and immune response to the Takeda acellular pertussis-component diphtheria-tetanus-pertussis (APDT) vaccine in children when immunization commenced at 2 months (group A) vs 3 months (group B) of age. DESIGN--Longitudinal, nonblinded, comparative study. SETTING--Pediatric well-child clinics. PARTICIPANTS--Healthy 50- to 98-day-old infants. RESULTS--Good antibody responses to lymphocytosis-promoting factor, filamentous hemagglutinin, agglutinogens, and pertactin occurred in both age groups after both the third and fourth vaccine doses. Both young age and transplacentally acquired maternal antibody independently and together have a suppressive effect on the response to the four antigens in this APDT vaccine. However, these effects appear to be minor. Vaccine reactions were mild; group A children had slightly but not significantly higher rates than group B children. CONCLUSION--The present US diphtheria and tetanus toxoids and pertussis vaccine immunization schedule should also be satisfactory with this acellular pertussis component vaccine.     

Efficacy and safety of acellular pertussis vaccine in Aichi Prefecture, Japan

A prominent increase of notified cases of pertussis was observed during discontinuation of pertussis immunization in Aichi Prefecture from 1975 to 1979. The patients were principally unimmunized children. After reintroduction of pertussis vaccine the number of cases decreased gradually and the decline has continued after the introduction of acellular pertussis vaccine. A retrospective survey of immunized schoolchildren also showed efficacy of the vaccine. To confirm the efficacy of acellular vaccine a prospective case contact study was conducted. Of 35 unimmunized children 29 developed clinically diagnosed pertussis, and of 52 children who received two or more doses of the vaccine only two developed disease after the household exposure. There were no serious systemic adverse reactions including high fever or encephalopathy. Severe local reaction occurred in 2.65/100,000 recipients of a third and fourth dose of the acellular vaccine.     

A ten year follow-up after immunization with a two component acellular pertussis vaccine

OBJECTIVES: To investigate the duration of antitoxin response and immunity to pertussis 10 years after priming with either two or three doses of a two component acellular pertussis vaccine or with three doses of a whole cell vaccine and then boostered with the acellular vaccine. SUBJECTS: At 11 years of age 207 of 304 (68%) children of the original cohort returned for a blood sample and 262 (86%) participated by answering a questionnaire. METHODS: Neutralizing antibodies to pertussis toxin (antitoxin) were analyzed by the Chinese hamster ovary cell assay. Clinical pertussis and pertussis exposure were investigated by a structured questionnaire. RESULTS: Measurable antitoxin was found in 77% of the samples, with no differences by type of vaccine or by the number of doses given for priming. A significant decrease of antibody concentration (P<0.001) was noted from the previous recall at 4 years of age, and significant titer rises were found for 14% of the children, irrespective of known exposure. Confirmed pertussis during follow-up, as defined in the study, was reported for 14 of 262 (5%) children. CONCLUSIONS: The study showed that antitoxin concentrations are maintained in a situation of endemic pertussis and indicated that the long term protection after an acellular booster was good, irrespective of type of vaccine or the number of doses of acellular vaccine given for priming.     

Long term serologic follow-up after pertussis immunization

Neutralizing antibodies to pertussis toxin (antitoxin) were determined in 201 blood samples from 4-year-old children. They had received primary immunization at 6 to 8 months of age with an acellular (n = 149) or a whole cell (n = 52) pertussis vaccine and 195 of them had received a booster dose of the acellular vaccine 9 to 16 months later. Data on exposure to pertussis and occurrence of pertussis were also collected. There was a rapid decrease of antitoxin between immediate postbooster titers and those measured 24 months later. This decrease per month was significantly greater than that after the primary immunization series (P less than 0.001). Neither the number nor the spacing of acellular vaccine doses given for primary series influenced the titers found 24 months after the booster. An antitoxin response was still measurable in 86% of the 196 four-year-old children. None of 19 exposed children developed whooping cough, which suggested that the antibody concentrations during the follow-up period were sufficient for protection. The results indicate a need for long term follow-up studies in the evaluation of new vaccines and immunization schedules.     

Booster response to acellular pertussis vaccine in children primed with acellular or whole cell vaccines

Few data are available on the effect of a booster dose of acellular pertussis vaccine in children primed as infants with acellular vaccine. We administered acellular pertussis vaccine (ACV) at 19 months to children immunized in infancy with ACV or whole cell vaccine. Forty-one infants had been randomly assigned to receive either ACV or whole cell vaccine at 2, 4 and 6 months of age. Antibody titers to pertussis toxin and filamentous hemagglutinin were significantly higher in ACV than whole cell vaccine recipients at 7 months; at 15 months antibody to filamentous hemagglutinin (but not pertussis toxin) remained significantly higher among those receiving ACV. At 19 months all 41 children received an ACV booster. Local and systemic reactions were few and minor and were equally distributed between the two groups. All children responded to booster with significant increases in antibody; these increases tended to be greater for those having been primed with ACV. ACV booster immunization appears safe and immunogenic, regardless of the vaccine given for primary immunization.     

Acellular pertussis vaccine composed of genetically inactivated pertussis toxin: safety and immunogenicity in 12- to 24- and 2- to 4-month-old children.

To determine whether a nontoxic derivative of pertussis toxin obtained by recombinant DNA technology, PT-9K/129G, is a good candidate for a new pertussis vaccine, we examined the safety and the immunogenicity in children of a vaccine containing 15 micrograms of PT-9K/129G protein and 0.5 mg of aluminum hydroxide per dose. Fifty-three children 12 to 24 months of age and 21 infants aged 2 to 4 months were injected with two and three doses, respectively. The vaccine did not induce significant local or systemic reactions and elicited an increase of antibody titer in more than 98% of the children. The geometric mean of the toxin-neutralizing titers increased after each dose and was 85 units in children given two doses and 196 units in those given three doses. Two children who had detectable antibody levels before the first immunization had a high response (greater than 320 units) to the first vaccine dose. The findings suggest that PT-9K/129G is a promising antigen to be included in the development of acellular pertussis vaccines.     

Adverse effects and sero-responses to an acellular pertussis/diphtheria/tetanus vaccine when combined with Haemophilus influenzae type b vaccine in an accelerated schedule

Acellular pertussis vaccines provide protection against pertussis with few adverse effects. Differences in the reactogenicity and immunogenicity of available pertussis vaccines may be influenced by the immunisation schedule employed. We assessed responses to an acellular pertussis, diphtheria, tetanus vaccine mixed with Haemophilus influenzae type b (Hib) vaccine, (PRP-T) given at age 2, 3 and 4 months. Parents kept a symptom diary for 3 days after each immunisation. Antibodies to diphtheria, tetanus, pertussis toxin and filamentous haemagglutinin were measured by enzyme immunoassay at 2 and 5 months. Results were compared with historical controls who received a combination whole-cell pertussis, diphtheria, tetanus/PRP-T vaccine in the same schedule. A total of 262 infants were recruited, of whom 251 were fully evaluated after three doses of vaccine. Systemic and most local reactions were less frequent following the acellular combination. Fever ≥38°C was reported after only 0.6% of doses. Redness or swelling ≥2.5 cm were unusual after the first two doses (2–5%), but rates rose to 13% after the third dose. Antibody responses to diphtheria and tetanus toxoids were lower, while those to pertussis antigens were higher, more uniform and less attenuated by pre-immunisation antibody than in infants who received the whole-cell combination. All infants achieved protective antibody titres of at least 0.1 IU/ml for diphtheria and 0.01 IU/ml for tetanus. Conclusion The acellular combination vaccine was immunogenic for diphtheria, tetanus and pertussis components and was associated with low rates of fever following immunisation. Received: 9 June 1998 / Accepted: 2 November 1998     

Immunogloblin E and G responses to pertussis toxin after booster immunization in relation to atopy, local reactions and aluminium content of the vaccines

The role of aluminium for IgG and IgE responses to pertussis toxin (PT), as well as for side effects, was investigated in 49 children with known atopy status. Primary immunization had been given with an adsorbed monocomponent or an adsorbed two-component acellular pertussis vaccine. The children were then randomized to receive a booster immunization with either aluminiumadsorbed or non-adsorbed, whole cell, pertussis vaccine. Both vaccines induced good IgG responses with the adsorbed vaccine giving higher post-booster levels (p < 0.05). The adsorbed vaccine was, however, associated with more local side effects (p < 0.05) and tended to induce higher PT-IgE responses than the non-adsorbed vaccine. Furthermore, individuals who had received the two-component vaccine as primary immunization had higher PT-IgE responses after the booster, compared with individuals initially receiving the monocomponent vaccine (p = 0.041). No correlation between PT-IgE and PT-IgG levels was seen in any of the groups. Total serum IgE levels correlated to PT IgE levels, particularly in children with atopy (r = 0.950, p < 0.001). The addition of aluminium to the pertussis vaccine, was, thus, associated with a stronger IgG antibody response, but tended also to induce a stronger IgE antibody response. The correlation between total IgE and PT-IgE, which was most prominent in children with atopy, indicates that the role of immunization for the development of allergy merits further studies.     

Safety and immunogenicity of acellular pertussis vaccine, combined with diphtheria and tetanus as the Japanese commercial Takeda vaccine, compared with the Takeda acellular pertussis component combined with Lederle's diphtheria and tetanus toxoids in two-, four- and six-month-old infants.

A double blind, randomized, controlled trial compared the safety and immunogenicity of an acellular pertussis vaccine formulated at Lederle using the Takeda acellular pertussis component combined with Lederle diphtheria and tetanus toxoids vaccines (APDT), with the commercially available Japanese Takeda vaccine (APDT-T/J) as a three-dose series to 2-, 4-, and 6-month-old children. Sera were analyzed for antibody to pertussis antigens: lymphocytosis-promoting factor; filamentous hemagglutinin; 69-kDa outer membrane protein; pertussis agglutinogens; neutralizing antibodies to LPF; and to diphtheria and tetanus toxoids. Information concerning local reactions and systemic events were collected daily for 10 days postimmunization. The overall reaction rate was low for both groups. There were no reactions that contraindicated subsequent vaccine and no serious adverse events. For local reactions statistically significant differences between the groups were seen only for a greater incidence of induration in the APDT group at 2 months (12% vs. 0%, P < 0.01), and at 4 months (8% vs. 0%, P = 0.4) compared to the APDT-T/J group. Of the few systemic reactions the only statistically significant difference between the vaccine groups was a greater incidence of fretfulness in the APDT group after the initial immunization (12% vs. 2%, P = 0.05). There were no statistically significant differences in the immune response between the two vaccines at the 7-month visit. We conclude that APDT is equivalent to the commercially available Takeda vaccine (APDT-T/J).     

Case-control study of vaccination history in relation to pertussis risk during an outbreak among school students

BACKGROUND: Between September and December 2003, an outbreak of pertussis occurred in Cass County, MO, mostly among adolescent school children. METHODS: We conducted a 1:2 matched case-control study among school children and used conditional logistic regression to evaluate risk factors for pertussis, including the total number of vaccine doses received, age at administration of each dose of vaccine and the type of vaccine (whole cell or acellular). RESULTS: Of all 127 pertussis cases reported in this outbreak, the majority were adolescents (10-19 years of age, 50%) and adults (20 years or older, 22%); only 10% were infants and children less than 5 years of age. Because the focus of our investigation was on school-aged children, we enrolled 237 students (79 cases and 158 controls) in our study. Students missing at least one dose of the vaccine had higher risk for pertussis than those who received all 5 doses (odds ratio [OR], 2.36; 95% confidence interval [CI], 1.17-4.77). Early administration of the fifth dose of the vaccine at age 4 years was significantly associated with risk for pertussis compared with vaccination at age 5 years (adjusted OR, 2.45; 95% CI, 1.16-5.16). A short time interval (<36 months) between the fourth and fifth doses of the vaccine also tended to increase the risk for pertussis, although this association was not statistically significant. The type of vaccine was not a significant risk factor. CONCLUSION: Administering all 5 doses of pertussis vaccine and the fifth dose at age 5 years with at least 36 months between the fourth and fifth doses provided the best protection against pertussis among children and adolescents in this outbreak.     

Comparison of acellular and whole-cell pertussis-component diphtheria-tetanus-pertussis vaccines in infants. The APDT Vaccine Study Group

In a multicenter, double-blind, randomized, longitudinal study, 252 children received licensed Lederle diphtheria-tetanus toxoids and pertussis vaccine adsorbed (DTP) at 2, 4, and 6 months of age, and 245 children received a DTP vaccine with the Lederle/Takeda acellular pertussis component (APDT) at the same ages. Both groups of children received APDT vaccine at 18 months of age. After each of the first three immunizations, APDT vaccine recipients had fewer local and systemic reactions than did DTP vaccinees. Reactions after the 18-month APDT vaccination were minimal in severity regardless of the vaccine previously received. Antibody responses to lymphocytosis-promoting factor and agglutinogens were more pronounced in DTP recipients; however, APDT recipients had a better serologic response to filamentous hemagglutinin, and responses to the 69K protein were equivalent. This APDT vaccine produces fewer reactions than the standard whole-cell DTP vaccine. The protective significance of the serologic responses to the APDT vaccine is unknown, but the greater response to filamentous hemagglutinin and equivalent response to the 69K protein compared with those to DTP vaccine seem promising.     

Protection Against Pertussis by Acellular Pertussis Vaccines (Takeda, Japan): Household Contact Studies in Kawasaki City, Japan

To evaluate the vaccine efficacy of an acellular pertussis vaccine which has been in clinical use in Japan since 1981, a retrospective study was performed by a questionnaire survey of secondary pertussis attacks through family contact in 146 children with pertussis diagnosed in the period from January 1981 through May 1988. In this study, acellular vaccine made by Takeda Pharmaceutical Company, which contains a high level of FHA (filamentous hemag-glutinin), a low level of PT (pertussis toxin) and a small amount of agglutinogen, was evaluated. Secondary pertussis attacks through family contact were found in 17 of 29 siblings (58.6%) not immunized with pertussis vaccine. On the other hand, 27 siblings immunized with Takeda's acellular vaccine were exposed to pertussis through family contact and a secondary attack was seen in only one of them (3.7%). The present study revealed an efficacy rate of 93.7% for Takeda's acellular pertussis vaccine.     

Immunogenicity and safety of a monovalent,multicomponent acellular pertussis vaccine in 15 month–6-year-old German children

Immunization against pertussis has been re-recommended for healthy children in Germany in 1991. In addition the former restriction of immunizing only in the first 2 years of life was abolished. In children born before 1991 immunization rates against pertussis were 15% or less. With the new recommendations physicians are now faced with an increasing demand of parents for catch-up vaccinations in these children. Since they were immunized against diphtheria and tetanus previously monovalent pertussis vaccines are needed for this indication. Therefore a monovalent, multicomponent acellular pertussis vaccine was studied in 249 German children 15 months to 6 years of age. Three doses were administered at 6–10 week intervals. Reactogenicity and antibody responses against the vaccine antigens pertussis toxin (PT), filamentous haemagglutinin (FHA), 69-kd antigen (pertactin) and fimbriae-2 (agglutinogen) were investigated. Local and systemic reactions were minimal in frequency and severity. Antibody responses against all vaccine antigens were pronounced with 93%–100% of vaccinees demonstrating at least four fold titre rises above pre-immunization after the third dose. These findings indicate that this monovalent, multicomponent acellular pertussis vaccine with excellent immunogenicity and low reactogenicity is an appropriate candidate for closing immunization gaps in older children in countries with previously low vaccination rates against pertussis. Based on the results of this study the monovalent acellular pertussis vaccine was licensed in Germany in January 1994.     

Antibody response to Bordetella pertussis antigens after immunization with American and Canadian whole-cell vaccines.

Because of apparent differences in the incidence and epidemiology of pertussis in the United States and Canada, we measured the antibody response to four Bordetella pertussis antigens and to a whole-bacteria preparation in children immunized with American and Canadian whole-cell pertussis vaccines. All infants received combined pertussis, tetanus, and diphtheria vaccines from one of two American manufacturers or a single Canadian manufacturer. The Canadian children received either oral poliomyelitis vaccine, inactivated poliomyelitis vaccine as a separate injection, or a product that combined inactivated poliomyelitis vaccine with diphtheria, tetanus, and pertussis components. The Canadian trivalent diphtheria, tetanus, and pertussis vaccine given with oral poliovirus vaccine induced lower anti-pertussis toxin antibody titers than did the American vaccines (p < or = to 0.05) but higher antifimbriae and anti-69-kilodalton outer-membrane protein (pertactin) antibody titers (p < or = to 0.02). Canadian children immunized with inactivated poliomyelitis vaccine either as a separate injection or as a combined diphtheria, tetanus, and pertussis vaccine had consistently lower pertussis antibody titers than did those who received oral poliomyelitis vaccine (p < or = 0.001). We conclude that there is a wide range of antibody responses to B. pertussis antigens after immunization with various whole-cell pertussis vaccines, and that these responses may be influenced by concurrent administration of other vaccines.