Preclinical study on an adsorbed acellular diphtheria- tetanus-pertussis (reduced-dose) combined vaccine: evaluation of reproductive safety and immunogenicity

Introduction The diphtheria, tetanus, and acellular pertussis combined vaccine (DTaP) is a trivalent formulation containing acellular pertussis antigens, diphtheria toxoid, and tetanus toxoid, and provides simultaneous protection against pertussis, diphtheria, and tetanus. This study aimed to systematically evaluate the effects of repeated intramuscular administration of an adsorbed acellular diphtheria-tetanus-pertussis (reduced-dose) combined vaccine (Tdacp) on gamete maturation, mating performance, fertility, and embryo-fetal development in Sprague-Dawley (SD) rats, thereby providing experimental evidence for its reproductive safety. Methods Sexually mature SD rats were randomly assigned, stratified by sex and body weight into four groups: negative control, adjuvant control, low-dose, and high-dose, with 40 rats per group (20 males and 20 females). Male and female rats were paired for mating according to group assignment and identification number. Animals received two intramuscular injections; the low-dose group received 0.25 mL/rat, whereas all other groups received 0.5 mL/rat. Evaluated parameters included clinical signs, food consumption, body weight, reproductive organ coefficients, estrous cycle characteristics in females, sperm parameters in males, embryo-fetal growth and development, and vaccine-induced antibody responses. Results Repeated intramuscular administration of Tdacp did not result in significant adverse effects on food consumption, body weight, or reproductive function in either the low-dose or high-dose group compared with the negative control group. Likewise, no treatment-related embryo-fetal developmental toxicity or teratogenic effects were observed. Although several embryo-fetal developmental parameters in the adjuvant control group, including implantation loss, fetal viability, embryo/fetal resorption, and selected skeletal ossification findings, differed from those in the negative control group, similar findings were not observed in the vaccine-treated groups. Immunogenicity analysis demonstrated positive antibody responses against diphtheria, tetanus, and pertussis antigens in both vaccine groups following immunization. Discussion These findings indicate that Tdacp has a favorable reproductive safety profile and good immunogenicity in SD rats. The results provide important nonclinical evidence to support its further clinical development. Manufactured using advanced chromatographic purification technology, this combined vaccine may contribute to the establishment and implementation of a life-course pertussis prevention and immunization strategy in China.