Antibody Response to Pertussis Vaccination in Pregnant and Non-Pregnant Women—The Role of Sex Hormones
Abstract
:1. Introduction
2. Methods
2.1. Study Design
2.2. Study Population
2.3. Blood Sampling
2.4. Questionnaires
2.5. Study Vaccine
2.6. Antibody Assays
2.7. 17β-Estradiol and Progesterone Quantitative Determination
2.8. Statistical Analyses
3. Results
3.1. Comparison of Anti-PT IgG Antibody Levels between Pregnant and Non-Pregnant Women
3.2. Multiple Logistic Regression Analysis—Pregnancy Status (Pregnant vs. Non-Pregnant Women) Assosiation with Anti-PT IgG Antibody Levels, Controlling for Other Variables
3.3. Estrogen and Progesterone Levels in Each Group of Pregnant and Non-Pregnant Women
3.4. Multiple Logistic Regression Analyses of the Association between Anti-PT IgG Antibody Levels and Sex Hormones
Association between Anti-PT IgG Antibody Levels and Estrogen
3.5. Association between Anti-PT IgG Antibody Levels and Progesterone
4. Discussion
4.1. There Are Several Strengths and Limitations of the Study
4.2. Comparison with Other Studies
4.3. Possible Mechanisms
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Kretsinger, K.; Broder, K.R.; Cortese, M.M.; Joyce, M.P.; Ortega-Sanchez, I.; Lee, G.M.; Tiwari, T.; Cohn, A.C.; Slade, B.A.; Iskander, J.K.; et al. Preventing tetanus, diphtheria, and pertussis among adults: Use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel. MMWR Recomm. Rep. 2006, 55, 1–37. [Google Scholar]
- Esposito, S.; Stefanelli, P.; Fry, N.K.; Fedele, G.; He, Q.; Paterson, P.; Tan, T.; Knuf, M.; Rodrigo, C.; Olevier, C.W.; et al. World Association of Infectious Diseases and Immunological Disorders (WAidid) and the Vaccine Study Group of the European Society of Clinical Microbiology and Infectious Diseases (EVASG). Pertussis Prevention: Reasons for Resurgence, and Differences in the Current Acellular Pertussis Vaccines. Front. Immunol. 2019, 10, 1344. [Google Scholar]
- Anis, E.; Moerman, L.; Ginsberg, G.; Karakis, I.; Slater, P.E.; Warshavsky, B.; Gosinov, R.; Grotto, I.; Marva, E. Did two booster doses for schoolchildren change the epidemiology of pertussis in Israel? J. Public Health Policy 2018, 39, 304–317. [Google Scholar] [CrossRef]
- Rendi-Wagner, P.; Tobias, J.; Moerman, L.; Goren, S.; Bassal, R.; Green, M.; Cohen, D. The seroepidemiology of Bordetella pertussis in Israel—Estimate of incidence of infection. Vaccine 2010, 28, 3285–3290. [Google Scholar] [CrossRef]
- Nieves, D.J.; Heininger, U. Bordetella pertussis. Emerg. Infect. 2016, 10, 311–339. [Google Scholar]
- Chang, I.-F.; Lee, P.-I.; Lu, C.-Y.; Chen, J.-M.; Huang, L.-M.; Chang, L.-Y. Resurgence of pertussis in Taiwan during 2009–2015 and its impact on infants. J. Microbiol. Immunol. Infect. 2019, 52, 542–548. [Google Scholar] [CrossRef]
- CDC. Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in pregnant women—Advisory Committee on Immuniza-tion Practices (ACIP), 2012. MMWR Morb. Mortal. Wkly. Rep. 2013, 62, 131–135. [Google Scholar]
- Langsam, D.; Anis, E.; Haas, E.J.; Gosinov, R.; Yechezkel, M.; Grotto, I.; Shmueli, E.; Yamin, D. Tdap vaccination during pregnancy interrupts a twen-ty-year increase in the incidence of pertussis. Vaccine 2020, 38, 2700–2706. [Google Scholar] [CrossRef]
- Anraad, C.; Lehmann, B.A.; Visser, O.; van Empelen, P.; Paulussen, T.G.; Ruiter, R.A.; Kamp, L.; van der Maas, N.A.; Barug, D.; Ruijs, W.L.; et al. Social-psychological determinants of maternal pertussis vaccination acceptance during pregnancy among women in the Netherlands. Vaccine 2020, 38, 6254–6266. [Google Scholar] [CrossRef]
- McCracken, S.; McCracken, S. Pregnancy—Do we really understand how the immune system tolerates us? BJOG Int. J. Obstet. Gynaecol. 2018, 125, 1388. [Google Scholar] [CrossRef] [Green Version]
- Robinson, D.P.; Klein, S.L. Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis. Horm. Behav. 2012, 62, 263–271. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Svensson-Arvelund, J.; Ernerudh, J.; Buse, E.; Cline, J.M.; Haeger, J.-D.; Dixon, D.; Markert, U.R.; Pfarrer, C.; De Vos, P.; Faas, M.M. The placenta in toxicology. Part II: Systemic and local immune adaptations in pregnancy. Toxicol. Pathol. 2014, 42, 327–338. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schlaudecker, E.P.; McNeal, M.M.; Dodd, C.N.; Ranz, J.B.; Steinhoff, M.C. Pregnancy Modifies the Antibody Response to Trivalent Influenza Immunization. J. Infect. Dis. 2012, 206, 1670–1673. [Google Scholar] [CrossRef] [PubMed]
- Fortner, K.B.; Swamy, G.K.; Broder, K.R.; Jimenez-Truque, N.; Zhu, Y.; Moro, P.L.; Liang, J.; Walter, E.B.; Heine, R.P.; Moody, M.A.; et al. Reactogenicity and immunogenicity of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in pregnant and nonpregnant women. Vaccine 2018, 36, 6354–6360. [Google Scholar] [CrossRef] [PubMed]
- Munoz, F.M.; Bond, N.H.; Maccato, M.; Pinell, P.; Hammill, H.A.; Swamy, G.K.; Walter, E.B.; Jackson, L.A.; Englund, J.A.; Edwards, E.B.; et al. Safety and immunogenicity of tetanus diphtheria and acellular pertussis (Tdap) immunization during pregnancy in mothers and infants: A randomized clinical trial. JAMA 2014, 311, 1760–1769. [Google Scholar] [CrossRef] [PubMed]
- Huygen, K.; Caboré, R.N.; Maertens, K.; Van Damme, P.; Leuridan, E. Humoral and cell mediated immune responses to a pertussis containing vaccine in pregnant and nonpregnant women. Vaccine 2015, 33, 4117–4123. [Google Scholar] [CrossRef]
- Ohfuji, S.; Fukushima, W.; Deguchi, M.; Kawabata, K.; Yoshida, H.; Hatayama, H.; Maeda, A.; Hirota, Y. Immunogenicity of a Monovalent 2009 Influenza A (H1N1) Vaccine Among Pregnant Women: Lowered Antibody Response by Prior Seasonal Vaccination. J. Infect. Dis. 2011, 203, 1301–1308. [Google Scholar] [CrossRef] [PubMed]
- Sakala, I.G.; Honda-Okubo, Y.; Fung, J.; Petrovsky, N. Influenza immunization during pregnancy: Benefits for mother and infant. Hum. Vaccines Immunother. 2016, 12, 3065–3071. [Google Scholar] [CrossRef] [Green Version]
- Craney, T.A.; Surles, J.G. Model-Dependent Variance Inflation Factor Cutoff Values. Qual. Eng. 2007, 14, 391–403. [Google Scholar] [CrossRef]
- Smith, R.; Smith, J.I.; Shen, X.; Engel, P.J.; Bowman, M.E.; McGrath, S.A.; Bisits, A.M.; McElduff, P.; Giles, W.B.; Smith, D. Patterns of Plasma Corticotropin-Releasing Hormone, Progesterone, Estradiol, and Estriol Change and the Onset of Human Labor. J. Clin. Endocrinol. Metab. 2009, 94, 2066–2074. [Google Scholar] [CrossRef] [Green Version]
- Mathur, R.; Landgrebe, S.; Williamson, H. Progesterone, 17-hydroxyprogesterone, estradiol, and estriol in late pregnancy and labor. Am. J. Obstet. Gynecol. 1980, 136, 25–27. [Google Scholar] [CrossRef]
- Ottesen, B.; Lebech, P.E. Plasma progesterone, serum estriol and plasma hpl determinations during the last trimester to detect changes before spontaneous labor: Comparison of progesterone assay using ria and cpb. Acta Obstet. Gynecol. Scand. 1979, 58, 423–427. [Google Scholar] [CrossRef]
- Konopka, C.K.; Morais, E.N.; Naidon, D.; Pereira, A.M.; Rubin, M.A.; Oliveira, J.F.; Mello, G.F. Maternal serum progesterone, estradiol and estriol levels in successful dinoprostone-induced labor. Braz. J. Med. Biol. Res. 2013, 46, 91–97. [Google Scholar] [CrossRef] [PubMed]
- Mesiano, S.; Chan, E.-C.; Fitter, J.T.; Kwek, K.; Yeo, G.; Smith, R. Progesterone Withdrawal and Estrogen Activation in Human Parturition Are Coordinated by Progesterone Receptor A Expression in the Myometrium. J. Clin. Endocrinol. Metab. 2002, 87, 2924–2930. [Google Scholar] [CrossRef]
- Boroditsky, R.S.; Reyes, F.I.; Winter, J.S.; Faiman, C. Maternal serum estrogen and progesterone concentrations preceding normal labor. Obstet. Gynecol. 1978, 51, 686–691. [Google Scholar]
- Klein, S.L.; Jedlicka, A.; Pekosz, A. The Xs and Y of immune responses to viral vaccines. Lancet Infect. Dis. 2010, 10, 338–349. [Google Scholar] [CrossRef]
- Sappenfield, E.; Jamieson, D.; Kourtis, A.P. Pregnancy and Susceptibility to Infectious Diseases. Infect. Dis. Obstet. Gynecol. 2013, 2013, 1–8. [Google Scholar] [CrossRef]
- Straub, R.H. The Complex Role of Estrogens in Inflammation. Endocr. Rev. 2007, 28, 521–574. [Google Scholar] [CrossRef] [Green Version]
- Cvoro, A.; Tatomer, D.; Tee, M.K.; Zogovic, T.; Harris, H.A.; Leitman, D.C. Selective estrogen receptor-beta agonists repress transcription of proinflammatory genes. J. Immunol. 2008, 180, 630–636. [Google Scholar] [CrossRef] [PubMed]
- Fu, B.; Tian, Z.; Wei, H. TH17 cells in human recurrent pregnancy loss and pre-eclampsia. Cell. Mol. Immunol. 2014, 11, 564–570. [Google Scholar] [CrossRef] [Green Version]
- Szekeres-Bartho, J.; Wegmann, T. A progesterone-dependent immunomodulatory protein alters the Th1Th2 balance. J. Reprod. Immunol. 1996, 31, 81–95. [Google Scholar] [CrossRef]
- Mor, G.; Cardenas, I. The Immune System in Pregnancy: A Unique Complexity. Am. J. Reprod. Immunol. 2010, 63, 425–433. [Google Scholar] [CrossRef] [Green Version]
- Maeda, Y.; Ohtsuka, H.; Tomioka, M.; Oikawa, M. Effect of progesterone on Th1/Th2/Th17 and regulatory T cell-related genes in peripheral blood mononuclear cells during pregnancy in cows. Vet. Res. Commun. 2013, 37, 43–49. [Google Scholar] [CrossRef]
- Bancroft, T.; Dillon, M.B.; Antunes, R.D.S.; Paul, S.; Peters, B.; Crotty, S.; Arlehamn, C.S.L.; Sette, A. Th1 versus Th2 T cell polarization by whole-cell and acellular childhood pertussis vaccines persists upon re-immunization in adolescence and adulthood. Cell. Immunol. 2016, 304–305, 35–43. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mills, K.H.; Ross, P.J.; Allen, A.C.; Wilk, M. Do we need a new vaccine to control the re-emergence of pertussis? Trends Microbiol. 2014, 22, 49–52. [Google Scholar] [CrossRef]
- Higgs, R.; Higgins, S.C.; Ross, P.J.; Mills, K.H.G. Immunity to the respiratory pathogen Bordetella pertussis. Mucosal Immunol. 2012, 5, 485–500. [Google Scholar] [CrossRef] [Green Version]
- Hendrikx, L.H.; Öztürk, K.; De Rond, L.G.H.; Veenhoven, R.H.; Sanders, E.A.M.; Berbers, G.A.M.; Buisman, A.-M. Identifying long-term memory B-cells in vaccinated children despite waning antibody levels specific for Bordetella pertussis proteins. Vaccine 2011, 29, 1431–1437. [Google Scholar] [CrossRef] [PubMed]
- Mills, K.H. Immunity to Bordetella pertussis. Microbes Infect. 2001, 3, 655–677. [Google Scholar] [CrossRef]
- Leef, M.; Elkins, K.L.; Barbic, J.; Shahin, R.D. Protective Immunity to Bordetella pertussis Requires Both B Cells and Cd4+ T Cells for Key Functions Other than Specific Antibody Production. J. Exp. Med. 2000, 191, 1841–1852. [Google Scholar] [CrossRef] [Green Version]
- Marcellini, V.; Mortari, E.P.; Fedele, G.; Gesualdo, F.; Pandolfi, E.; Midulla, F.; Leone, P.; Stefanelli, P.; Tozzi, A.E.; Carsetti, R.; et al. Protection against Pertussis in Humans Correlates to Elevated Serum Antibodies and Memory B Cells. Front. Immunol. 2017, 8, 1158. [Google Scholar] [CrossRef] [Green Version]
- Da Silva, A.R.; Babor, M.; Carpenter, C.; Khalil, N.; Cortese, M.; Mentzer, A.J.; Seumois, G.; Petro, C.D.; Purcell, L.A.; Vijayanand, P.; et al. Th1/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters. J. Clin. Investig. 2018, 128, 3853–3865. [Google Scholar] [CrossRef] [Green Version]
- Lima, J.; Martins, C.; Leandro, M.J.; Nunes, G.; Sousa, M.-J.; Branco, J.C.; Borrego, L.-M. Characterization of B cells in healthy pregnant women from late pregnancy to post-partum: A prospective observational study. BMC Pregnancy Childbirth 2016, 16, 139. [Google Scholar] [CrossRef] [Green Version]
- Medina, K.L.; Smithson, G.; Kincade, P.W. Suppression of B lymphopoiesis during normal pregnancy. J. Exp. Med. 1993, 178, 1507–1515. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Medina, K.L.; Kincade, P.W. Pregnancy-related steroids are potential negative regulators of B lymphopoiesis. Proc. Natl. Acad. Sci. USA 1994, 91, 5382–5386. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hlobeňová, T.; Ŝefc, L.; Chang, K.-T.; Savvulidi, F.; Michalová, J.; Nečas, E. B-lymphopoiesis gains sensitivity to subsequent inhibition by estrogens during final phase of fetal development. Dev. Comp. Immunol. 2012, 36, 385–389. [Google Scholar] [CrossRef] [PubMed]
- Zhang, L.; Chang, K.-K.; Li, M.-Q.; Li, D.-J.; Yao, X.-Y. Mouse endometrial stromal cells and progesterone inhibit the activation and regulate the differentiation and antibody secretion of mouse B cells. Int. J. Clin. Exp. Pathol. 2013, 7, 123–133. [Google Scholar]
Characteristics of Study Participants | Non Pregnant Women (n = 74) | Pregnant Women (n = 174) |
---|---|---|
Ethnicity, n (%) | ||
Jews | 67 (90.5%) | 148 (85.0%) |
Arabs | 7 (9.5%) | 26 (15.0%) |
Age (years) | ||
Mean (SD) | 24.5 (8.5) | 26.0 (3.3) |
Median (min, max) | 19.5 (18.0, 45.0) | 26.0 (18.0, 31.0) |
Height (cm) | ||
Mean (SD) | 162.5 (7.2) | 163.0 (6.8) |
Median (min, max) | 161.0 (147.0, 182.0) | 162.0 (148.0, 184.0) |
Weight (kg) | ||
Mean (SD) | 58.5 (9.2) | 75.3 (13.3) |
Median (min, max) | 57.0 (42.0, 8) | 74.0 (50.0, 133.0) |
BMI kg/m2 | ||
Mean (SD) | 22.1 (3.2) | 28.4 (4.4) |
Median (min, max) | 21.7 (16.4, 28.7) | 27.8 (20.0, 44.0) |
Smoking status, n (%) | ||
Yes | 11 (14.9) | 15 (9.0) |
No | 63 (85.1) | 159 (91.0) |
Variables in the Model | β Coefficient | Odds Ratio | 95% CI | p |
---|---|---|---|---|
Pregnancy (Yes vs. No) | −0.885 | 0.413 | 0.190, 0.899 | 0.026 |
Age, years | −0.044 | 0.957 | 0.906, 1.011 | 0.119 |
BMI, kg/m2 | −0.024 | 0.976 | 0.914, 1.043 | 0.470 |
Smoking, (Yes vs. No) | 0.034 | 1.034 | 0.495, 2.161 | 0.928 |
Variables in the Model | 95% CI | Odds Ratio | β Coefficient | p |
---|---|---|---|---|
Non-pregnant (n = 74) | ||||
Estrogen (GMC) | −0.663 | 0.515 | 0.134, 1.975 | 0.333 |
Age, years | −0.094 | 0.911 | 0.848, 0.978 | 0.010 |
BMI, kg/m2 | −0.134 | 0.875 | 0.713, 1.072 | 0.197 |
Smoking, (Yes vs. No) | −1.472 | 0.229 | 0.023, 2.251 | 0.206 |
Pregnant (n = 174) | ||||
Estrogen (GMC) | −2.641 | 0.071 | 0.017, 0.292 | <0.0001 |
Age, years | 0.053 | 1.054 | 0.946, 1.175 | 0.340 |
BMI, kg/m2 | −0.012 | 0.988 | 0.916, 1.066 | 0.758 |
Smoking, (Yes vs. No) | 0.587 | 1.799 | 0.733, 4.416 | 0.200 |
Variables in the Model | 95% CI | Odds Ratio | β Coefficient | p |
---|---|---|---|---|
Non-pregnant (n = 74) | ||||
Progesterone (GMC) | 0.489 | 1.631 | 0.713, 3.733 | 0.246 |
Age, years | −0.092 | 0.912 | 0.850, 0.979 | 0.011 |
BMI, kg/m2 | −0.123 | 0.885 | 0.723, 1.083 | 0.235 |
Smoking, (Yes vs. No) | −1.560 | 0.210 | 0.021, 2.140 | 0.188 |
Pregnant (n = 174) | ||||
Progesterone (GMC) | −1.205 | 0.300 | 0.116, 0.772 | 0.013 |
Age, years | 0.066 | 1.068 | 0.962, 1.186 | 0.220 |
BMI, kg/m2 | −0.011 | 0.989 | 0.920, 1.063 | 0.760 |
Smoking, (Yes vs. No) | 0.458 | 1.581 | 0.673, 3.713 | 0.294 |
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Peer, V.; Muhsen, K.; Betser, M.; Green, M.S. Antibody Response to Pertussis Vaccination in Pregnant and Non-Pregnant Women—The Role of Sex Hormones. Vaccines 2021, 9, 637. https://doi.org/10.3390/vaccines9060637
Peer V, Muhsen K, Betser M, Green MS. Antibody Response to Pertussis Vaccination in Pregnant and Non-Pregnant Women—The Role of Sex Hormones. Vaccines. 2021; 9(6):637. https://doi.org/10.3390/vaccines9060637
Chicago/Turabian StylePeer, Victoria, Khitam Muhsen, Moshe Betser, and Manfred S Green. 2021. "Antibody Response to Pertussis Vaccination in Pregnant and Non-Pregnant Women—The Role of Sex Hormones" Vaccines 9, no. 6: 637. https://doi.org/10.3390/vaccines9060637
APA StylePeer, V., Muhsen, K., Betser, M., & Green, M. S. (2021). Antibody Response to Pertussis Vaccination in Pregnant and Non-Pregnant Women—The Role of Sex Hormones. Vaccines, 9(6), 637. https://doi.org/10.3390/vaccines9060637