Repeated-Dose Toxicity, Biodistribution, and Shedding Assessments With a ChAd155 Respiratory Syncytial Virus Vaccine Candidate Evaluated in Rabbits and Rats.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections (LRTI) in infants, and toddlers and vaccines are not yet available. A pediatric RSV vaccine (ChAd155-RSV) is being developed to protect infants against RSV disease. The ChAd155-RSV vaccine consists of a recombinant replication-deficient chimpanzee-derived adenovirus (ChAd) group C vector engineered to express the RSV antigens F, N, and M2-1. The local and systemic effects of three bi-weekly intramuscular injections of the ChAd155-RSV vaccine was tested in a repeated-dose toxicity study in rabbits. After three intramuscular doses, the ChAd155-RSV vaccine was considered well-tolerated. Changes due to the vaccine-elicited inflammatory reaction/immune response were observed along with transient decreases in platelet count without physiological consequences, already reported for other adenovirus-based vaccines. In addition, the biodistribution and shedding of ChAd155-RSV were also characterized in two studies in rats. The distribution and persistence of the ChAd155-RSV vaccine candidate was consistent with other similar adenovector-based vaccines, with quantifiable levels of ChAd155-RSV observed at the injection site (muscle) and the draining lymph nodes up to 69 days post administration. The shedding results demonstrated that ChAd155-RSV was generally not detectable in any secretions or excreta samples. In conclusion, the ChAd155-RSV vaccine was well-tolerated locally and systemically.

Reproductive safety evaluation of L-Ergothioneine.

L-Ergothioneine is a naturally occurring histidine-derived betaine (CAS No: 497-30-3) synthesized by bacteria and fungi, and found ubiquitously in plants and animals. It is present in many human foodstuffs. We evaluated the potential reproductive toxicity of L-Ergothioneine in Sprague-Dawley rats. L-Ergothioneine was administered at concentrations of 0.1, 0.3 or 0.9% in diet to F0 males (for 10 weeks before pairing and 3 weeks during pairing) and F0 females (for 13 weeks before pairing, during pairing and gestation, and until day 5 of lactation). Systemic exposure increased with dose-level, but not dose proportionally, suggesting saturation of uptake mechanisms. No clinical signs of toxicity were observed and there were no effects of L-Ergothioneine treatment on mating and reproductive performance or parameters of fertility. All animals mated within a similar number of days and pregnancy rates were uniformly high in control and treated groups. There were no effects of treatment with L-Ergothioneine on the duration of gestation, pre- and post-implantation losses, number of pups delivered and viability index, or on litter parameters (litter size, clinical signs, body weight or sex ratio) and the repartition of found dead/cannibalized pups. In conclusion, L-Ergothioneine was well tolerated and without adverse effects on the reproductive parameters evaluated.