Heplisav-B: which tox species, and why?

“The CpG 1018 adjuvant alone was evaluated in 3 genotoxicity studies, 2 safety escalation studies (rabbit and baboons) and 3 repeated toxicology studies (mice, rats, and cynomolgus monkeys).”

“These studies demonstrated that despite some known differences in TLR9 expression pattern between rodent and primate hematopoietic cells, the 1018 ISS adjuvanted vaccine is immunogenic in all three animal species. This provides support to the choice of mice, rat and monkeys (baboons and cynomolgus monkeys) for the safety studies.”

“Repeat-dose toxicity and reproductive and developmental toxicity studies were performed with HBsAg plus CpG 1018 and single-dose, repeat-dose and genotoxicity studies were performed with the CpG 1018 adjuvant alone.”

“The CpG 1018 adjuvant alone was evaluated in 3 genotoxicity studies, 2 safety escalation studies (rabbit and baboons) and 3 repeated toxicology studies (mice, rats, and cynomolgus monkeys).”

“HBsAg plus CpG 1018 was also tested in rats in a reproductive and developmental toxicity study which assessed the potential effects on mating behavior, fertility, gestation, embryo-fetal development, parturition, lactation and maternal behavior”

“No studies assessing the carcinogenicity of Heplisav B or 1018 ISS adjuvant have been performed. This is acceptable for this type of product in line with EMAs guidelines for vaccines and adjuvants and compliant with ICH S1A, considering that the exposure to this vaccine will be sporadic.”

“Repeat-dose toxicity and reproductive and developmental toxicity studies were performed with HBsAg plus CpG 1018 and single-dose, repeat-dose and genotoxicity studies were performed with the CpG 1018 adjuvant alone.”