Skip Navigation

Prevalence of Antibody to Bordetella pertussis Antigens in Serum Specimens Obtained from 1793 Adolescents and Adults

  1. James D. Cherry1,
  2. Swei-Ju Chang1,
  3. David Klein2,
  4. Martin Lee1,
  5. Steve Barenkamp7,
  6. David Bernstein5,
  7. Robert Edelman3,
  8. Michael D. Decker6,a,
  9. David P. Greenberg4,
  10. Wendy Keitel8,
  11. John Treanor9, and
  12. Joel I. Ward1
  1. 1University of California-Los Angeles (UCLA) Center for Vaccine Research, and Research and Education Institute, Harbor-UCLA Medical Center, David Geffen School of Medicine at UCLA, Torrance, California
  2. 2National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda
  3. 3Department of Medicine and the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore
  4. 4University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, Pennsylvania
  5. 5Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Ohio
  6. 6Departments of Preventive Medicine and Medicine (Infectious Diseases), Vanderbilt University School of Medicine, Nashville, Tennessee
  7. 7Saint Louis University, Missouri
  8. 8Baylor College of Medicine, Houston, Texas
  9. 9University of Rochester, New York
  1. Reprints or correspondence: Dr. James D. Cherry, Dept. of Pediatrics, MDCC 22–442, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1752 (jcherry{at}mednet.ucla.edu).

  • ↵a Current affiliation: Scientific and Medical Affairs Department, Aventis Pasteur, Swiftwater, Pennsylvania.

 
Next Section

Abstract

Serum specimens were obtained from all subjects in the adolescent and adult acellular pertussis (aP) vaccine efficacy trial before and after immunization to study the prevalence of IgG and IgA antibody and geometric mean titers to 4 Bordetella pertussis antigens. Of 1793 adolescents and adult subjects who received aP vaccine, only 20%, 68%, 59%, and 39% had concentrations of IgG antibodies to pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3, respectively, that were greater than or equal to the limit of quantitation of the enzyme-linked immunosorbent assay used in the analysis. There was minimal variation in antibody prevalence with respect to geographic area, age, sex, or race.

Before the development of pertussis vaccine, it was observed that reported cases of pertussis had a cyclic pattern, with peaks occurring every 2–5 years [1, 2]. For >30 years, pertussis has been well controlled in many countries by immunization of children. However, despite the reduction in the incidence of reported cases, the cyclic pattern of peaks every 2–5 years still occurs. Because the cycles of reported cases of pertussis have not changed despite the marked reduction in disease incidence, it has been realized that pertussis immunization of children controls the disease but not the circulation of Bordetella pertussis [1–4].

During the past 20 years, numerous studies have documented that a significant percentage of prolonged cough illnesses among adolescents and adults are due to B. pertussis, with serological studies indicating a high rate of unrecognized infections in adolescents and adults [2–8]. In the recently completed adolescent and adult acellular pertussis (aP) vaccine efficacy trial (APERT), serum specimens were obtained from all participants before and 1 month after pertussis immunization. We have used these serum specimens to study the prevalence of IgG and IgA antibodies and geometric mean titers to 4 B. pertussis antigens in a large number of subjects of different ages from 8 geographic regions of the United States.

Patients and methods. APERT was a prospective trial involving 2781 healthy adolescents and adults aged 15–65 years at 8 study centers who received either an aP vaccine or a control vaccine during the period of July 1997 through December 1998. Serum specimens from all subjects were collected before and after immunization, and analysis of antibodies to selected B. pertussis antigens was performed on serum specimens obtained from 1793 subjects, either before immunization (for aP vaccine recipients) or after immunization (for control vaccine recipients). Study sites included Baylor College of Medicine (Houston, TX), Cincinnati Children's Hospital (OH), Saint Louis University (MO), the University of Maryland (Baltimore, MD), the University of Rochester (NY), Vanderbilt University (Nashville, TN), the University of Pittsburgh (PA), and the University of California-Los Angeles Center for Vaccine Research.

IgA and IgG antibody to pertussis toxin, filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) were determined by ELISA using a modification of method described elsewhere [3, 8–11]. The limits of quantitation—the lower bound below which the precision of assay quantitation decreases—of the assay for IgG and IgA antibody to pertussis toxin was 6 ELISA units (EU)/mL and for IgG and IgA antibody to FHA, PRN, and FIM was 8 EU/mL.

Ninety-five percent confidence intervals for proportions were determined using the large-sample normal approximation, except in instances in which the actual proportions were near 0% or 100%. In these circumstances, the exact method of Clopper and Pearson was used [12]. Geometric mean titers were determined using logarithmic-transformed data.

Informed consent was obtained from all study participants. Human experimentation guidelines of the US Department of Health and Human Services and those of the institutional review boards of the 8 study sites and the National Institutes of Health (Bethesda, MD) were followed.

Results. A summary of antibody prevalence data and geometric mean titers is presented in table 1. As can be seen, only 20% of the subjects had concentrations of IgG antibody to pertussis toxin of ⩾6 EU/mL. In contrast, 68%, 59%, and 39% had concentrations of IgG antibody to FHA, PRN, and FIM of ⩾8 EU/mL, respectively. The geometric mean titers to pertussis toxin, FHA, PRN, and FIM were 2.2, 12.7, 10.1, and 5.0 EU/mL, respectively. The percentages of serum specimens with concentrations of IgA antibody to pertussis toxin, FHA, and PRN that were greater than or equal to the limit of quantitation or twice the limit of quantitation were less than the corresponding percentages of IgG antibody, although the percentages were similar proportionally. In contrast, the percentage of IgA values to FIM that were greater than or equal to the limit of quantitation and 2 times the limit of quantitation were higher than the corresponding IgG percentages.

Table 1
View larger version:
Table 1

Data on the geometric mean titers (GMTs) and prevalence of antibody to Bordetella pertussis antigen (relative to the ELISA-based limit of quantitation [LOQ]) in serum specimens obtained from adolescents and adults.

The geometric mean titers and prevalences of IgG antibody concentrations that were greater than or equal to the limit of quantitation of ELISA for pertussis toxin, FHA, PRN, and FIM are presented according to age group in table 2. With the exception of a higher percentage of 15–20-year-old subjects with pertussis toxin IgG antibody concentrations greater than or equal to the limit of quantitation, the age-related difference was small. Of interest, the 15–20-year-old age group had the lowest percentage (8%) of IgA antibody to pertussis toxin among the 9 age groups analyzed.

Table 2
View larger version:
Table 2

Age-based data on the geometric mean titers (GMTs) and concentrations of IgG antibody to Bordetella pertussis antigens in serum samples obtained from adolescents and adults.

The geometric mean titers and prevalences of IgG antibody concentrations greater than or equal to the limit of quantitation of the ELISA used to detect pertussis toxin, FHA, PRN, and FIM were examined for each of the 8 geographic regions. There were no meaningful differences by region. With 1 exception, the IgA antibody concentrations in serum specimens from each region also were similar. The outlier value, which was noted for specimens in the Cincinnati region, was 4% greater than or equal to the limit of quantitation of the ELISA used to detect pertussis toxin. This is 2–8-fold lower than the values noted in the other regions.

The geometric mean titers and prevalence of IgG antibody concentrations greater than or equal to the limit of quantitation of ELISA for pertussis toxin, FHA, PRN, and FIM in serum specimens collected from study subjects was evaluated on the basis of sex and race. Overall, females and Asians tended to have lower percentages of IgG and IgA antibody concentrations that were greater than or equal to the limit of quantitation of ELISA, but the differences were slight.

Discussion. In a study of prolonged cough illnesses in UCLA students performed over a 30-month period during 1986–1989, it was found that cases of pertussis occurred throughout the period [3]. This led to the suggestion that B. pertussis cough illnesses were endemic in adolescents and adults and that they were the source of outbreaks of reported pertussis in susceptible children. Subsequently, a number of studies involving adolescents and adults with prolonged cough illnesses have noted a high percentage of the illnesses due to B. pertussis infection [2, 4, 7]. Infection with B. pertussis regularly elicits both IgG and IgA antibody responses to pertussis toxin, FHA, PRN, and FIM [13]. Primary immunization of children results in IgG antibody responses but not IgA responses to the same antigens if these antigens are present in the vaccine. Previous surveys of IgA antibody, which was used as a marker of past infection rather than previous immunization, indicate that unrecognized infections commonly occur in the United States during childhood [9, 10].

Antibody to pertussis toxin is specific for past infection with B. pertussis, whereas antibody to FHA, PRN, and FIM can also be due to infection with other Bordetella species [7, 13]. In addition, antibody to FHA may also be the result of cross-reacting antibodies to Mycoplasma pneumoniae proteins and to other unidentified agents [3, 7].

The finding of a higher percentage of 15–20-year-old patients with concentrations of IgG antibody to pertussis toxin that are higher than the limit of quantitation is of interest and similar to that noted in a Nashville study involving serum specimens collected during 1985–1990 [14]. Cattaneo et al. [14] suggested that such findings are characteristic of B. pertussis infections in adolescents with waning immunity. This may be the case, but our failure to note a similar increased percentage of serum specimens with pertussis toxin IgA antibody was surprising. However, because IgA antibody is relatively short-lived, it is possible that the increased incidence of infections due to waning vaccine-induced immunity occurred before the age of 15 years. If this were true, patients in this age group might be significantly better protected against B. pertussis infection during the ages of 15–20 years, and, therefore, there might be a lower percentage of such patients with IgA antibody to pertussis toxin.

The failure to find meaningful differences in geometric mean titers and antibody prevalence by geographic area or age in this study, coupled with the fact that all studies of prolonged cough illnesses in adolescents and adults have noted relatively frequent B. pertussis infections, support the concept of endemic circulation of the organism among adolescents and adults. However, it is difficult to interpret the serological results with regard to potential susceptibility of individual adolescents and adults. If antibody to pertussis toxin is important for preventing infection, it might be expected that 80% of the study subjects would develop pertussis if exposed. On the other hand, if antibody to FHA, PRN, and FIM are involved in preventing infection, then one would expect a less susceptible adolescent and adult population.

In 2 trials, the children who received pertussis toxin toxoid vaccines and developed very high titers of pertussis toxin antibody were modestly protected from typical pertussis disease but had little protection against mild disease [15–17]. In 2 nested household contact studies, serological correlates of immunity were determined [18, 19]. Both studies found that antibody to PRN was most important in protection but that antibody to pertussis toxin and FIM also contributed to this protection. In 1 of these 2 trials, low levels of antibody to PRN were protective against both mild and typical disease, and this protection was augmented by high levels of pertussis toxin antibody [18]. On the basis of the above data, it would appear that few of the adolescent and adult subjects in our present study had protective levels of pertussis toxin antibody. Although the majority have elevated PRN concentrations, these values may be the result of cross-reacting antibody, which may or may not offer protection after exposure to B. pertussis.

Overall, the data presented in this report suggest a uniform susceptibility by age and geographic area to B. pertussis infection after exposure. These data tend to support a universal vaccination program for adults as well as adolescents when adult-formulated dTaP vaccines become available.

Previous SectionNext Section

Acknowledgments

Financial support. National Institute of Allergy and Infectious Diseases (contract 1-A115124).

Potential conflicts of interest. J.D.C.: Speaker's bureau for GlaxoSmithKline and Aventis. R.E.: Research funding from Aventis Pasteur Connaught. M.D.: Employed by Aventis Pasteur; member of speaker's bureaus for Aventis Pasteur, Chiron, GlaxoSmithKline, Pasteur Merieux, Connaught, Merck, and Wyeth; consultant for GlaxoSmithKline, Meade Johnson, Medicalliance, Pasteur Merieux, Connaught, Merck, and PRO/COM International; and research funding from Chiron, GlaxoSmithKline, Merck, and Wyeth. All other authors: no conflicts.

  • Received March 3, 2004.
  • Accepted May 13, 2004.
Previous Section
 

References

  1. ↵
    1. Fine PE,
    2. Clarkson JA
    . The recurrence of whooping cough: possible implications for assessment of vaccine efficacy. Lancet 1982;1:666-9.
    MedlineWeb of Science
  2. ↵
    1. Feigin RD,
    2. Cherry JD
    1. Cherry JD,
    2. Heininger U
    . Pertussis and other Bordetella infections. In: Feigin RD, Cherry JD, editors. Textbook of pediatric infectious diseases. 5th ed. Philadelphia: W.B. Saunders; 2003. p. 1588-608.
  3. ↵
    1. Mink CM,
    2. Cherry JD,
    3. Christenson P,
    4. et al
    . A search for Bordetella pertussis infection in university students. Clin Infect Dis 1992;14:464-71.
    Abstract/FREE Full Text
  4. ↵
    1. Cherry JD
    . Epidemiological, clinical, and laboratory aspects of pertussis in adults. Clin Infect Dis 1999;28(Suppl 2):112-7.
    CrossRef
    1. Deville JG,
    2. Cherry JD,
    3. Christenson PD,
    4. et al
    . Frequency of unrecognized Bordetella pertussis infections in adults. Clin Infect Dis 1995;21:639-42.
    Abstract/FREE Full Text
    1. Strebel P,
    2. Nordin J,
    3. Edwards K,
    4. et al
    . Population-based incidence of pertussis among adolescents and adults, Minnesota, 1995–1996. J Infect Dis 2001;183:1353-9.
    Abstract/FREE Full Text
  7. ↵
    1. Vincent JM,
    2. Cherry JD,
    3. Nauschuetz WF,
    4. et al
    . Prolonged afebrile nonproductive cough illnesses in American soldiers in Korea: a serological search for causation. Clin Infect Dis 2000;30:534-9.
    Abstract/FREE Full Text
  8. ↵
    1. Hodder SL,
    2. Cherry JD,
    3. Mortimer EA Jr,
    4. Ford AB,
    5. Gornbein J,
    6. Papp K
    . Antibody responses to Bordetella pertussis antigens and clinical correlations in elderly community residents. Clin Infect Dis 2000;31:7-14.
    Abstract/FREE Full Text
  9. ↵
    1. Cherry JD,
    2. Beer T,
    3. Chartrand SA,
    4. et al
    . Comparison of values of antibody to Bordetella pertussis antigen in young German and American men. Clin Infect Dis 1995;20:1271-4.
    Abstract/FREE Full Text
  10. ↵
    1. Deen JL,
    2. Mink CA,
    3. Cherry JD,
    4. et al
    . Household contact study of Bordetella pertussis infections. Clin Infect Dis 1995;21:1211-9.
    Abstract/FREE Full Text
  11. ↵
    1. Rose NR,
    2. Friedman H,
    3. Fahey JL
    1. Manclark C,
    2. Meade BD,
    3. Burstyn DG
    . Serological response to Bordetella pertussis. In: Rose NR, Friedman H, Fahey JL, editors. Manual of clinical laboratory immunology. 3rd ed. Washington, DC: American Society for Microbiology; 1986. p. 388-94.
  12. ↵
    1. Clopper CJ,
    2. Pearson E
    . The use of confidence or fiducial limits illustrated in the case of binomial. Biometrika 1934;26:404-13.
    FREE Full Text
  13. ↵
    1. Stehr K,
    2. Cherry JD,
    3. Heininger U,
    4. et al
    . A comparative efficacy trial in Germany in infants who received either the Lederle/Takeda acellular pertussis component DTP (DTaP) vaccine, the Lederle whole-cell component DTP vaccine, or DT vaccine. Pediatrics 1998;101:1-11.
    Abstract/FREE Full Text
  14. ↵
    1. Cattaneo LA,
    2. Reed GW,
    3. Haase DH,
    4. Wills MJ,
    5. Edwards KM
    . The seroepidemiology of Bordetella pertussis infections: a study of persons aged 1–65 years. J Infect Dis 1996;173:1256-9.
    Abstract/FREE Full Text
  15. ↵
    1. Cherry JD,
    2. Olin P
    . The science and fiction of pertussis. Pediatrics 1999;104:1381-4.
    FREE Full Text
    1. Storsaeter J,
    2. Hallander HO,
    3. Blackwelder WC
    . Pertussis antibodies, protection, and vaccine efficacy after household exposure. Am J Dis Child 1992;146:167-72.
    Abstract/FREE Full Text
  17. ↵
    1. Storsaeter J,
    2. Olin P
    . Relative efficacy of two acellular pertussis vaccines during three years of passive surveillance. Vaccine 1992;10:142-4.
    CrossRefMedlineWeb of Science
  18. ↵
    1. Cherry JD,
    2. Gornbein J,
    3. Heininger U,
    4. Stehr K
    . A search for serologic correlates of immunity to Bordetella pertussis cough illnesses. Vaccine 1998;16:1901-6.
    CrossRefMedlineWeb of Science
  19. ↵
    1. Storsaeter J,
    2. Hallander HO,
    3. Gustafsson L,
    4. Olin P
    . Levels of anti-pertussis antibodies related to protection after household exposure to Bordetella pertussis. Vaccine 1998;16:1907-16.
    CrossRefMedlineWeb of Science
| Table of Contents

This Article

  1. Clin Infect Dis. (2004) 39 (11): 1715-1718. doi: 10.1086/425003
  1. AbstractFree
  2. » Full Text (HTML)Free
  3. Full Text (PDF)Free

Classifications

Share

  1. Email this article

Navigate This Article

Current Issue

  1. March 1, 2012 54 (5)
  1. Clinical Infectious Diseases
  1. Alert me to new issues

Most