Safety and immunogenicity of simultaneous versus sequential tetanus, diphtheria, acellular pertussis vaccine and inactivated influenza vaccine in pregnant women

Objectives: To assess the safety and immunogenicity of simultaneous versus sequential tetanus, diphtheria, acellular pertussis vaccine (Tdap) and quadrivalent inactivated influenza vaccine (IIV4) in pregnant woman and transplacental antibody transfer at delivery. Methods: We conducted a pilot randomized, open-label clinical trial. Pregnant women received IIV4 and Tdap on the same day (simultaneous at Visit 1) or ∼21 days apart (IIV4 then Tdap, sequential at Visit 4). Data were collected on reactogenic events (days 1-8 after Visits 1 and 4) and pregnancy outcomes through delivery. Pre- and post-vaccination (∼21 days per vaccination) serum samples were analyzed for antibodies to pertussis toxin (PT), pertactin (PRN), filamentous hemagluttinin (FHA) (multiplex assay); diphtheria and tetanus toxoids (enzyme-linked immunosorbent assay); and influenza A (H1N1, H3N2), and influenza B (Victoria and Yamagata lineage) (hemagglutination inhibition assay) antigens. Statistical significance testing was not performed in this small study. Results: 41 pregnant women were randomized to the simultaneous group versus 40 to the sequential group. The median gestational age at randomization in the simultaneous and sequential groups were 29.1 and 28 weeks, respectively. Moderate/severe injection site pain at the IIV4 site (15% simultaneous, 5.4% sequential) and moderate/severe body ache and fatigue (after Visits 1 or 4), occurred more frequently in the simultaneous versus sequential group. No women sought medical attention for a vaccine reaction or had a vaccine-related serious adverse event. Similar proportions of women in each group had adverse pregnancy outcomes of preterm birth, small for gestational age, low birth weight, preeclampsia, and chorioamnionitis. Most women achieved post-vaccination seroprotective levels for tetanus (99%), diphtheria (96%), influenza A (≥93%) and influenza B (≥63%) antibodies. Some patterns were observed for lower maternal and infant pertussis and influenza antibodies in the simultaneous versus sequential group. Conclusion: Compared to sequential administration, simultaneous IIV4 and Tdap vaccination appeared to be associated with increased reactogenicity and lower maternal and cord blood antibody levels to some pertussis and influenza antigens. A larger sample size would be required to determine statistical and clinical significance of these findings. Similar pregnancy outcomes were observed after both vaccination schedules. Learning Objectives: Learners will be able to describe one safety and one immunogenicity result of a pilot study of simultaneous versus sequential dosing of Tdap and IIV in pregnancy.