Impact of timing between tetanus, diphtheria, and pertusis and SARS-CoV-2 messenger RNA vaccinations during pregnancy on SARS-CoV-2 antibody levels at delivery

OBJECTIVE: Administration of the tetanus, diphtheria, and acellular pertussis (Tdap) and the SARS-CoV-2 vaccines is recommended during pregnancy without any restriction on timing between vaccinations.1ACOG Committee Opinion No. 741: Maternal immunization.Obstet Gynecol. 2018; 131 (e214–7)Google Scholar We sought to study if timing between both vaccines interferes with the maternal SARS-CoV-2 antibody response.2Uhr JW Möller G. Regulatory effect of antibody on the immune response.Adv Immunol. 1968; 8: 81-127Crossref PubMed Scopus (449) Google Scholar STUDY DESIGN: Patients admitted for delivery ≥34 weeks’ gestation between February 8, 2021 and September 27, 2021, and who received 2 doses of a SARS-CoV-2 messenger RNA vaccination (Pfizer-BioNTech or Moderna) at least 14 days before delivery were included in this study. Patients who also received a Tdap vaccination between 27 and 36 weeks of gestation (Tdap) were compared with patients who had a confirmation of no Tdap vaccination receipt during the pregnancy (no Tdap). Vaccination dates and obstetrical data were abstracted from the clinical records. Semiquantitative maternal and umbilical cord blood antispike immunoglobulin G (anti-S IgG) levels were analyzed at delivery.3Kubiak JM Murphy EA Yee J et al.Severe acute respiratory syndrome coronavirus 2 serology levels in pregnant women and their neonates.Am J Obstet Gynecol. 2021; 225 (73.e1–7)Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar Differences in maternal IgG levels and placental transfer ratio to neonates between Tdap and no Tdap groups were studied using Wilcoxon rank sum tests. The number of weeks elapsed between receipt of the Tdap vaccine and receipt of dose 2 of a SARS-CoV-2 vaccine was calculated irrespective of which vaccine was received first. The relationship between gestational age at dose 2 of a SARS-CoV-2 vaccination and maternal IgG levels at delivery was studied using Spearman correlation and linear regression analysis in both the Tdap and no Tdap groups. In the Tdap group, a mixed analysis of variance (ANOVA) test was used to determine if the number of weeks elapsed between the 2 vaccinations and gestational age at SARS-CoV-2 vaccination contributed to variance in the antibody data. This study was approved by the Weill Cornell Medicine institutional review board and was a secondary analysis of 473 of 485 patients published previously.4Yang YJ Murphy EA Singh S et al.Association of gestational age at coronavirus disease 2019 (COVID-19) vaccination, history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and a vaccine booster dose with maternal and umbilical cord antibody levels at delivery.Obstet Gynecol. 2022; 139: 373-380Crossref PubMed Scopus (51) Google Scholar,5Prabhu M Murphy EA Sukhu AC et al.Antibody response to coronavirus disease 2019 (COVID-19) messenger RNA vaccination in pregnant women and transplacental passage into cord blood.Obstet Gynecol. 2021; 138: 278-280Crossref PubMed Scopus (79) Google Scholar RESULTS: Among the 453 Tdap patients and the 32 no Tdap patients, no patient had a known history of SARS-CoV-2 infection (no history of positive SARS-CoV-2 test, negative antinucleocapsid antibody test, and no clinical history of infection). There was no significant difference in the anti-S IgG levels in the full cohort (P=.14) (Figure, A) or in a subcohort of patients who received a Tdap vaccination within 2 weeks of a SARS-CoV-2 vaccination (P=.7) (Figure, B). No differences were observed in the placental transfer ratio (Figure, C) between the groups. Maternal IgG levels were linearly associated with gestational age at dose 2 of a SARS-CoV-2 vaccination in both populations studied (no Tdap group: rho=0.64; P=8.1e-05; Tdap group: rho=0.52, P<2.2e-16) (Figure, D). A mixed ANOVA analysis demonstrated that the time elapsed between SARS-CoV-2 vaccination and Tdap vaccination did not significantly contribute to variance in maternal IgG levels at delivery (P=.377), whereas gestational age at time of SARS-CoV-2 vaccination significantly influenced maternal IgG at delivery (P=8.681e-07), which is consistent with previous findings.3Kubiak JM Murphy EA Yee J et al.Severe acute respiratory syndrome coronavirus 2 serology levels in pregnant women and their neonates.Am J Obstet Gynecol. 2021; 225 (73.e1–7)Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 4Yang YJ Murphy EA Singh S et al.Association of gestational age at coronavirus disease 2019 (COVID-19) vaccination, history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and a vaccine booster dose with maternal and umbilical cord antibody levels at delivery.Obstet Gynecol. 2022; 139: 373-380Crossref PubMed Scopus (51) Google Scholar, 5Prabhu M Murphy EA Sukhu AC et al.Antibody response to coronavirus disease 2019 (COVID-19) messenger RNA vaccination in pregnant women and transplacental passage into cord blood.Obstet Gynecol. 2021; 138: 278-280Crossref PubMed Scopus (79) Google Scholar CONCLUSION: Differences in the number of weeks that elapsed between Tdap and SARS-CoV-2 vaccinations do not lead to significant differences in the maternal SARS-CoV-2 antibody levels at delivery, suggesting that no specific schedule between the 2 vaccines is indicated. Our study did not contain patients with coadministration of the 2 vaccines and is limited by cohort sizes. Effects on the immune response to Tdap and a follow-up on the efficacy of vaccinations need to be conducted.