Many antigens for Bordetella pertussis. Prof. Edwards analyzes the response to Acellular and Whole Cell Pertussis vaccines, with a special focus on maternal vaccination. To learn more, visit: www.waidid.org

1. Immune Responses:
Whole Cell and Acellular Pertussis
Vaccines
Kathryn M. Edwards MD
Sarah H. Sell and Cornelius Vanderbilt Professor
Department of Pediatrics
Vanderbilt University
Nashville, TN

2. Bordetella pertussis: Many Antigens
• Pertussis toxin (PT)
• Filamentous
hemagglutinin (FHA)
• Pertactin (PRN)
• Fimbrial agglutinogens
(FIM)
Fimbriae
FHA
Adenylate
cyclase
toxin
Pertactin
TCF
Dermonecrotic
toxin
TCF
Pertussis
toxin
What immune response to what antigen?

3. Vaccines Used in the NIH-funded MAPT

4. WCV
ACV
PT: Reverse Cumulative Distribution
Curves after Primary Vaccination

5. Pediatrics 1995;96;557
Febrile Response to Pertussis Vaccines in Infants

6. NIH-Sponsored Acellular Pertussis Vaccine
Efficacy Trials (Sweden and Italy)
Vaccine Manufacturer Vaccine Composition Efficacy Trial Location
SmithKline Beecham PT and FHA 59% Sweden
Connaught Laboratories PT, FHA, PRN, AG 85% Sweden
Connaught Laboratories Whole cell 48% Sweden
36% Italy
SmithKline Beecham PT, FHA, PRN 84% Italy
Chiron-Biocine PT, FHA, PRN 84% Italy
AG=agglutinogens; FHA = filamentous hemagglutinin; PRN = pertactin; PT = pertussis toxoid.
Adapted from Gustafsson et al6, Greco et al7, and Trollfors et al12.

7. 7 Mos. 22 Months
No. GMTs No. GMTs
IgG-PT
DTPwc 449 1.2 (1.1-1.3) 332 1.1 (1.1-1.2)
DTPa3 CB 486 94.3 (88.8-100.3) 403 4.5 (4.0-5.0)
DTPa3 GSK 476 51.3 (47.9-54.9) 389 2.7 (2.4-3.0)
DT 161 1.0 (1.0-1.1) 127 1.1 (1.0-1.2)
IgG-FHA
DTPwc 449 5.03 (4.7-5.8) 332 1.6 (1.4-1.8)
DTPa3 CB 486 52.6 (49.1-56.3) 403 4.7 (4.2-5.4)
DTPa3 GSK 476 146.9 (138.3-156.1) 389 11.4 (10.2-12.8)
DT 161 1.5 (1.3-1.6) 127 1.2 (1.0-1.3)
IgG-PRN
DTPwc 449 9.8 (8.6-11.3) 332 2.3 (2.1-2.5)
DTPa3 CB 486 136.6 (127.0-146.8) 403 9.9 (8.9-11.1)
DTPa3 GSK 476 274.2 (253.6-296.7) 389 17.9 (16.1-20.1)
DT 161 1.6 (1.6-1.7) 127 1.6 (1.5-1.7)
PT-neutralizing antibodies
DTPwc 237 23.0 (21.4-24.6) 176 21.4 (20.2-22.7)
DTPa3 CB 251 787.6 (718.2-863.5) 208 148.7 (124.7-177.4)
DTPa3 GSK 239 223.0 (203.7-259.7) 190 67.9 (56.0-82.3)
DT 81 22.0 (20.2-23.9) 60 21.2 (18.8-23.7)
DTPwc,Whole-cell DTP vaccine; DT, diphtheria and tetanus toxoids.
Antibody Titers to Acellular and Whole Cell DTP Vaccines

10. Th1 Response
With Infection

11. Edwards and Decker: Plotkin Vaccines

12. Rapid antibody response after Tdap in Adults

16. Conclusions
• Acellular vaccines (aP) are immunogenic, but
humoral immune responses vary with vaccine
• Pertussis antibody titers rapidly decline
• Whole cell vaccines vary in immunogenicity
• aP priming generates mixed Th1/Th2 response
• Pertussis disease generates Th1 response
• Previously primed individuals generate rapid
antibody response after vaccination

17. Mooi and de Greeff Lancet Infect Dis 2007

19. Maternal Transfer of Pertussis Antibody
Antigen (ELISA)
GMT (95% CI)
Maternal Sera Cord Sera
PT 5 (2-13) 14 (6-32)
FHA 41 (26-66) 27 (15-49)
Aggln 34 (23-50) 35 (24-51)
Van Savage J, Decker MD, Edwards KM, Sell SH, Karzon DT.
J. Infect. Dis. 161:487, 1990

22. Maternal Vaccination Prevents Leukocytosis, not
Colonization

26. Impact of Tdap on infant disease?

29. Immune Responses and Antibody Decay after
Immunization of Postpartum Women with Tetanus
and diphtheria toxoids and acellular pertussis
vaccines (Tdap)
Fortner KB1, Hunter DL2, McDonald WL2,
Rock MT2, Edwards KM2
1Division Maternal-Fetal Medicine, Vanderbilt University
2Division Pediatric Infectious Disease, Vanderbilt University
Are Tdap Vaccines Needed with Each Pregnancy?

30. Serum ELISA IgG Antibody Geometric Mean Titer
(GMT) Results by Individual Antigen
0
20
40
60
80
100
120
Day 0 2 Weeks 6 Weeks 6 Months
GMTand95%CI
Serum IgG PT
0
50
100
150
200
Day 0 2 Weeks 6 Weeks 6 Months
GMTand95%CI
Serum IgG FHA
0
200
400
600
800
1000
1200
1400
Day 0 2 Weeks 6 Weeks 6 Months
GMTand95%CI
Serum IgG PRN
0
500
1000
1500
2000
2500
Day 0 2 Weeks 6 Weeks 6 Months
GMTand95%CI
Serum IgG FIM

31. Safety of Tdap in Pregnant Women:
Study Design
• Prospective, observational
• Study population:
• 375 healthy pregnant women at ≥ 20 weeks 0 days
gestation through ≤ 34 weeks 0 days gestation and
their infants
• 225 non-pregnant women of reproductive age
with similar characteristics as pregnant women

32. Tdap Pregnant Women Enrollment
32
Vaccine
History
Yes (%) No (%) Unknown (%)
Prior Tdap 53 28 19
Prior Td/TT 67 10 23
Prior Tdap or
Td/TT
84 9 7

33. Local Reactions
in 361 Pregnant Women
Local Symptom None (%) Mild (%) Moderate (%) Severe* (%)
Pain 31 51 17 <1
Tenderness 18 62 19 <1
Swelling 82 12 5 1
Redness 87 7 4 2
* < 1% indicates only 2 pregnant women had such severe reaction.
33

34. Severe Local Reactions:
Pregnant Women
• a
34

35. Systemic Reactions
in 361 Pregnant Women
Systemic Rx None (%) Mild (%) Moderate (%) Severe* (%)
Fever
(≥ 100°F)** >99 <1 <1 0
Feverishness 92 4 3 <1
Malaise 67 22 10 <1
Body aches 76 16 7 <1
Headaches 70 23 6 <1
* < 1% indicates ≤ 3 pregnant women had such severe reaction.
**Temperature (°F): two subjects with moderate fever (100.4 °F and 100.9°F)
Median: 97.8 °F
Interquartile range: 97.5 to 98.3 °F 35

36. Pertussis IgA Antibody Titers in Breast Milk
Abu Raya: Vaccine 2014

38. Conclusions
• Maternal vaccination with acellular
pertussis vaccines is protective
against disease, but not infection
• Need to assess immune responses in
infants to primary vaccination
• Continued study of the changing
epidemiology of pertussis is needed