Which animal species did regulators accept for approved vaccines?

“The Applicant has provided two DART studies with RSVPreF3 (without adjuvant): one in rabbit (doses of 120 μg antigen) and one in rat (doses of 48 μg antigen). In addition, the report from a DART study with the complete product (i.e., RSVPreF3/AS01E; full human dose, 120 μg PreF3) in rabbit was provided.”

“Levels of anti-RSVPreF3 IgG antibodies were increased (measured at Day 32 and 57) in 80% of females and all males administered RSVPreF3 and in 80-90% of females and all males administered RSVPreF3 adjuvanted with AS01B in the first study.”

“Four repeated-dose toxicity studies were carried out in rabbits and one in rats.”

“Animal model: As stated by the sponsor, the rat was chosen “because of its use as a predictor of reproductive toxic change in man and the requirement for a rodent species by regulatory agencies.”

“Serological analysis demonstrated that unlike controls or adjuvant receiving animals, vaccine-treated rabbits showed a seroconversion in the repeat-dose toxicity study.”

“Serological analysis demonstrated that unlike controls or adjuvant receiving animals, vaccine-treated rabbits showed a seroconversion in the repeat-dose toxicity study.”

“The pivotal repeat-dose toxicity study was conducted with the SC route. Results showed that five weekly SC injections with RIV3 were locally and systemically well tolerated in rats.”

“RIV3 at the human dose induced an active immune response to the three strains in all rat dams from the vaccine group. The exposure of foetuses and pups to vaccine-specific maternal antibodies was also demonstrated.”

“A 10-week repeat-dose toxicity study was performed in BALB/c mice.”

“In both exploratory studies, it was demonstrated that the vaccine was immunogenic in rats and that an anti-HPV antibody response was seen for each HPV type present in the vaccine. These results show that the rat is an appropriate animal model for investigating the potential toxic effects related to administration of Gardasil.”

“Toxicology studies supporting the safety of the 9vHPV vaccine included 3 GLP-compliant studies in rats consisting of: i) a repeat-dose toxicity study (with local tolerance and non-GLP immunogenicity assessments), ii) an intramuscular developmental toxicity and immunogenicity study with female fertility and embryo-foetal evaluation and iii) an intramuscular developmental toxicity and immunogenicity study with postnatal evaluation.”

“the 9vHPV vaccine induced humoral immune responses against all 9 HPV serotypes (HPV Type 6, -11, -16, -18, -33, -31, -45, -52, and -58) following one or four intramuscular injections to rats at all dose levels, as a pharmacological effect.”

“The absence of toxicity was evaluated after repeated administrations in the rat according to treatment schedules mimicking a human vaccination scheme (i.e., 3 injections at monthly intervals).”

“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.”

“As given in the WHO and EMA guidance, rat and rabbit are considered acceptable species for vaccine nonclinical safety studies and therefore generally chosen for the single dose/local tolerance and repeat dose toxicology studies.”

“Serological analysis demonstrated seroconversion in all vaccine treated animals and none in the saline-treated controls, confirming that the rabbit is an immunological responder species for the RTS,S/AS01B candidate vaccine formulation.”

“A repeat-dose GLP-compliant study with SARS-CoV-2 rS in rabbits was performed, with or without the adjuvant Matrix-M1. In addition, 6 GLP-compliant repeated dose toxicity studies in rats and rabbits with other vaccines in combination with Matrix-M1, or Matrix-M1 alone, were provided, in which the toxicity of Matrix-M1 was evaluated.”

“A non-GLP pilot study in rats indicated that SARS-CoV-2 rS adjuvanted with Matrix-M1 is immunogenic in female and male rats following one and two immunisations.”

“Toxicology: Three toxicity studies and an intramuscular embryo-fetal developmental and pre- and post-natal reproductive toxicity study in rats were submitted.”

“The suitability of rats as a model was demonstrated by collected immunogenicity data.”

“Most studies were done in rat and rabbit, as both species demonstrated a good antibody response.”

“Most studies were done in rat and rabbit, as both species demonstrated a good antibody response.”