908
The Longevity of the Immune Response to Filamentous Hemagglutinin and Pertussis Toxin in Patients with Pertussis in a Semiclosed Community Takashi Tomoda, Hideo Ogura, and Takanobu Kurashige
Department of Pediatrics, Kochi Medical School, Nankoku. and Division ofPediatrics, Higashi-Koehl National Hospital, Kochi, Japan
Titers of antibodies to the filamentous hemagglutinin (FHA) and pertussis toxin (PT) of Bordetella pertussis were studied in patients from a semiclosed community after an outbreak of the disease in 1985 and in the general population. In convalescent-phase serum obtained after B.
pertussisinfection in patients in the semiclosed community, high anti-FHA IgG and anti-PT IgG
Filamentous hemagglutinin (FHA) is a surface-associated adherence protein of Bordetella pertussis and plays an important role in the pathogenesis of pertussis by mediating bacteria-host cell interaction [1, 2]. Pertussis toxin (PT) has a variety of biologic characteristics [3, 4]. FHA and PT stimulate humoral and cellular immune responses in humans after clinical disease and vaccination [3-5]. It is known that the degree of inhibition of B. pertussis infection depends on the quantity of protective antibodies. In addition, a number of studies on the seroepidemiology of pertussis [6-10] have demonstrated that there are differences in antibody titers among age groups, countries, and environments. In June 1985, we experienced an outbreak of B. pertussis infection in one ward of an institution for severely handicapped people and measured anti-FHA and anti-PT antibody titers 4 and 8 weeks after the onset of illness. Six years later, we investigated the fluctuation of the antibodies.
Materials and Methods Subjects. One group was 21 severely handicapped patients (age, 37.5 ± 12.1; 9 female, 12 male; 5 had been vaccinated with a whole cell pertussis vaccine [DPT] and none had a history of pertussis) affected by the 1985 institutional outbreak of B. pertussis infection. The other group was 21 patients (age, 33.4 ±
Received 19 February 1992; revised 6 May 1992. Informed consent was obtained from parents or guardians of all participants. Financial support: Ministry of Health and Welfare of Japan (Study of Vaccinations and Adverse Reactions). Reprints or correspondence: Dr. T. Tomoda, Department of Pediatrics, Kochi Medical School, Kochi 783, Japan. The Journal of Infectious Diseases
1992;166:908-10
© 1992 by The University of Chicago. All rights reserved. 0022-1899/92/6604-0034$01.00
9.8; 10 female, II male; 4 had been vaccinated with DPT and none had a history of pertussis) from a different ward in the same institution with no evidence ofhaving had pertussis during the 1985 outbreak. The diagnosis of pertussis was based on typical coughing attacks of pertussis and one or more of the following: a nasopharyngeal culture positive for B. pertussis. peripheral leukocytosis (> 15,000/mm 3 with >70% lymphocytes), or a fourfold or greater increase in bacterial agglutinin titer in blood samples obtained 4 and 8 weeks after the onset of illness. The study population consisted of 31 patients with cerebral palsy, 6 with severe epilepsy, 2 with postencephalitis, and 2 with congenital metabolic disorders. None showed evidence ofimmunologic disorders. After the 1985 outbreak, we also measured anti-FHA IgG and anti-PT IgG antibodies in 15 medical personnel (age, 30.8 ± 5.4; 8 nurses, 7 physicians) who were staff of Kochi Medical School Hospital, which is different from the institution for severely handicapped people, and 24 healthy volunteers (age 22.3 ± 3.9; 9 female, 15 male) who were students at Kochi Medical School, all of whom had received the DPT vaccine. Serum antibody. Serum samples for antibody determination were collected from patients, medical personnel, and healthy volunteers by venipuncture in January 1991. Stock sera from patients and medical personnel stored at -80 aC since 1985 were also used. Antibodies to FHA and PT were measured by ELISA by the method of Sato et al. [11]. Units were calculated by multiplying the relative titers by 100, the assigned value for the reference serum (gift ofY. Sato, National Institute of Health, Tokyo). FHA and PT antigens (gifts of Cherno-Sero-Therapeutic Institute, Kumamoto, Japan) were purified from culture supernatants of B. pertussis Tohama and detoxified with formalin using the method of Sato et al. [12]. DNA synthesis. Peripheral blood mononuclear cells (PBMC) were obtained from heparinized venous blood by Ficoll-Conray density gradient centrifugation and resuspended at a final concentration of 5 X 105/mL in RPMI 1640 supplemented with penicillin G, streptomycin, glutamine, sodium bicarbonate, and 10% fetal calf serum. Aliquots (100 #LL) of the mononuclear cell suspension were then cultured with 1.8 #Lg of
Downloaded from http://jid.oxfordjournals.org/ at University of Manitoba on September 14, 2015
titers were observed; these titers tended to disappear over the next 5 years. On the other hand, among the medical staff, high anti-FHA and anti-PT IgG titers persisted during the same 5-year period. It seems likely that anti-FHA and anti-PT IgG levels reflect the frequency of exposure to the bacteria and that B. pertussis is widespread in the Japanese population. Although the antiFHA IgG antibody response decreased in patients from the semiclosed community, the cellular immune response was maintained.
1ID 1992; 166 (October)
Concise Communications
FHA/mL or 1.2 J.Lg of PT/mL for 4 days in 5% CO2 at 37°C. Eighteen hours before the cultures were terminated, I J.LCi of [6-3H]thymidine (specific activity, 19.3 Ci/rnmol; NEN, Boston) was added, and incorporation of radioactivity into the cells was determined. Data were statistically analyzed by Student's t test.
A 200
Results
The differences in antibody titers induced may depend not on the immunogenic potential of the vaccine but on the frequency ofsubsequent contact with the bacterium. In the present study, we determined the persistence of anti-FHA IgG titers and cellular immunity elicited by B. pertussis infection and vaccination in open and closed populations. The medical personnel had high titers of anti-FHA and anti-P'I' IgG antibodies, probably because they had many opportunities to come into contact with B. pertussis. Although their anti-FHA IgG levels were lower than those of
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The Longevity of the Immune Response to Filamentous Hemagglutinin and Pertussis Toxin in Patients with Pertussis in a Semiclosed Community Takashi Tomoda, Hideo Ogura, and Takanobu Kurashige
Department of Pediatrics, Kochi Medical School, Nankoku. and Division ofPediatrics, Higashi-Koehl National Hospital, Kochi, Japan
Titers of antibodies to the filamentous hemagglutinin (FHA) and pertussis toxin (PT) of Bordetella pertussis were studied in patients from a semiclosed community after an outbreak of the disease in 1985 and in the general population. In convalescent-phase serum obtained after B.
pertussisinfection in patients in the semiclosed community, high anti-FHA IgG and anti-PT IgG
Filamentous hemagglutinin (FHA) is a surface-associated adherence protein of Bordetella pertussis and plays an important role in the pathogenesis of pertussis by mediating bacteria-host cell interaction [1, 2]. Pertussis toxin (PT) has a variety of biologic characteristics [3, 4]. FHA and PT stimulate humoral and cellular immune responses in humans after clinical disease and vaccination [3-5]. It is known that the degree of inhibition of B. pertussis infection depends on the quantity of protective antibodies. In addition, a number of studies on the seroepidemiology of pertussis [6-10] have demonstrated that there are differences in antibody titers among age groups, countries, and environments. In June 1985, we experienced an outbreak of B. pertussis infection in one ward of an institution for severely handicapped people and measured anti-FHA and anti-PT antibody titers 4 and 8 weeks after the onset of illness. Six years later, we investigated the fluctuation of the antibodies.
Materials and Methods Subjects. One group was 21 severely handicapped patients (age, 37.5 ± 12.1; 9 female, 12 male; 5 had been vaccinated with a whole cell pertussis vaccine [DPT] and none had a history of pertussis) affected by the 1985 institutional outbreak of B. pertussis infection. The other group was 21 patients (age, 33.4 ±
Received 19 February 1992; revised 6 May 1992. Informed consent was obtained from parents or guardians of all participants. Financial support: Ministry of Health and Welfare of Japan (Study of Vaccinations and Adverse Reactions). Reprints or correspondence: Dr. T. Tomoda, Department of Pediatrics, Kochi Medical School, Kochi 783, Japan. The Journal of Infectious Diseases
1992;166:908-10
© 1992 by The University of Chicago. All rights reserved. 0022-1899/92/6604-0034$01.00
9.8; 10 female, II male; 4 had been vaccinated with DPT and none had a history of pertussis) from a different ward in the same institution with no evidence ofhaving had pertussis during the 1985 outbreak. The diagnosis of pertussis was based on typical coughing attacks of pertussis and one or more of the following: a nasopharyngeal culture positive for B. pertussis. peripheral leukocytosis (> 15,000/mm 3 with >70% lymphocytes), or a fourfold or greater increase in bacterial agglutinin titer in blood samples obtained 4 and 8 weeks after the onset of illness. The study population consisted of 31 patients with cerebral palsy, 6 with severe epilepsy, 2 with postencephalitis, and 2 with congenital metabolic disorders. None showed evidence ofimmunologic disorders. After the 1985 outbreak, we also measured anti-FHA IgG and anti-PT IgG antibodies in 15 medical personnel (age, 30.8 ± 5.4; 8 nurses, 7 physicians) who were staff of Kochi Medical School Hospital, which is different from the institution for severely handicapped people, and 24 healthy volunteers (age 22.3 ± 3.9; 9 female, 15 male) who were students at Kochi Medical School, all of whom had received the DPT vaccine. Serum antibody. Serum samples for antibody determination were collected from patients, medical personnel, and healthy volunteers by venipuncture in January 1991. Stock sera from patients and medical personnel stored at -80 aC since 1985 were also used. Antibodies to FHA and PT were measured by ELISA by the method of Sato et al. [11]. Units were calculated by multiplying the relative titers by 100, the assigned value for the reference serum (gift ofY. Sato, National Institute of Health, Tokyo). FHA and PT antigens (gifts of Cherno-Sero-Therapeutic Institute, Kumamoto, Japan) were purified from culture supernatants of B. pertussis Tohama and detoxified with formalin using the method of Sato et al. [12]. DNA synthesis. Peripheral blood mononuclear cells (PBMC) were obtained from heparinized venous blood by Ficoll-Conray density gradient centrifugation and resuspended at a final concentration of 5 X 105/mL in RPMI 1640 supplemented with penicillin G, streptomycin, glutamine, sodium bicarbonate, and 10% fetal calf serum. Aliquots (100 #LL) of the mononuclear cell suspension were then cultured with 1.8 #Lg of
Downloaded from http://jid.oxfordjournals.org/ at University of Manitoba on September 14, 2015
titers were observed; these titers tended to disappear over the next 5 years. On the other hand, among the medical staff, high anti-FHA and anti-PT IgG titers persisted during the same 5-year period. It seems likely that anti-FHA and anti-PT IgG levels reflect the frequency of exposure to the bacteria and that B. pertussis is widespread in the Japanese population. Although the antiFHA IgG antibody response decreased in patients from the semiclosed community, the cellular immune response was maintained.
1ID 1992; 166 (October)
Concise Communications
FHA/mL or 1.2 J.Lg of PT/mL for 4 days in 5% CO2 at 37°C. Eighteen hours before the cultures were terminated, I J.LCi of [6-3H]thymidine (specific activity, 19.3 Ci/rnmol; NEN, Boston) was added, and incorporation of radioactivity into the cells was determined. Data were statistically analyzed by Student's t test.
A 200
Results
The differences in antibody titers induced may depend not on the immunogenic potential of the vaccine but on the frequency ofsubsequent contact with the bacterium. In the present study, we determined the persistence of anti-FHA IgG titers and cellular immunity elicited by B. pertussis infection and vaccination in open and closed populations. The medical personnel had high titers of anti-FHA and anti-P'I' IgG antibodies, probably because they had many opportunities to come into contact with B. pertussis. Although their anti-FHA IgG levels were lower than those of
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