Effects of maternal exposure to an adsorbed acellular diphtheria-tetanus-pertussis (reduced-dose) combined vaccine on prenatal and postnatal development in Sprague-Dawley rats: a preclinical study.

Introduction: The resurgence of pertussis poses a severe threat to infants under 3 months of age due to an inherent early-life "immunity gap." While maternal immunization with the tetanus, diphtheria, and acellular pertussis (Tdap/Tdacp) vaccine effectively mitigates this risk globally, no such vaccine is currently licensed for maternal use in China. This preclinical study aimed to systematically evaluate the reproductive and developmental toxicity, as well as the immunogenicity, of an independently developed Tdacp candidate vaccine in Sprague-Dawley (SD) rats. Methods: Eighty-eight female SD rats were randomly assigned to four groups: negative control, adjuvant control, low-dose (0.25 ml/rat), and high-dose (0.5 ml/rat). The vaccine was administered via intramuscular injection at three time points to maximize exposure: one week prior to mating, on gestation day 6 (GD 6), and on lactation day 7 (LD 7). Systemic assessments included maternal general toxicity, reproductive performance, and embryo-fetal development. Additionally, postnatal survival, physical growth, and neuro-reflex developmental landmarks of F1 offspring were monitored. Antigen-specific antibody titers in both F0 dams and F1 offspring were quantified to evaluate immunogenicity and maternal antibodies transfer. Results: Repeated maternal exposure to the Tdacp vaccine elicited no treatment-related maternal systemic toxicity; body weight, food consumption, and gestation length remained comparable to controls. No adverse effects were observed on mating, fertility, or uterine implantation. Furthermore, the vaccine did not negatively impact F1 offspring survival, sex ratio, physical morphology, or the acquisition of neuro-reflex milestones. Immunologically, the vaccine induced robust and stable antibody responses against all specific antigens, including pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), diphtheria toxoid (DT), and tetanus toxoid (TT), in F0 dams. Crucially, high titers of these antigen-specific antibodies were detected in the F1 offspring, demonstrating successful passive transfer of maternal antibodies to the offspring. Conclusion: The investigational Tdacp vaccine demonstrated a highly favorable safety profile with no evidence of maternal, reproductive, or developmental toxicity. Coupled with its robust immunogenicity and efficient maternal antibody transfer, these findings provide pivotal preclinical validation to support advancing the vaccine into human clinical trials for maternal immunization.