Discussion
miscarriage, TTS
ADVERSE EVENTS, RVF, MISCARRIAGE, CORONAVIRUS, THROMBOSIS WITH THROMBOCYTOPENIA SYNDROME
There are currently no vaccines for use against RVF in humans, leaving the world vulnerable to public health emergencies associated with RVF epidemics. For this reason, the WHO has prioritised development of RVF countermeasures and compiled a target product profile to guide vaccine development.A scalable manufacturing process for ChAdOx1-vectored vaccines has been developed and successfully used for the ChAdOx1 nCoV-19 (AZD1222) COVID-19 vaccine that is now deployed in over 180 countries globally,Post-marketing surveillance of adenovirus-vectored COVID-19 vaccines, including ChAdOx1 nCoV-19, uncovered a very rare association with thrombosis with thrombocytopenia syndrome (TTS). The biological mechanism underlying TTS is incompletely understood and it remains unknown whether it may also affect adenovirus-vectored vaccines that do not deliver coronavirus antigens.In keeping with our previous livestock studies,The short follow-up duration of this first-in-human trial precluded durability assessments of immune responses generated by vaccination. However, the high nAb titres and the robust IFNγ cellular response detected within 2 weeks post-vaccination augur well for reactive use of the vaccine during RVF outbreaks where rapid induction of immunity is necessary to protect individuals at highest risk of exposure.This first-in-human trial had several limitations, including the small sample size which was sufficient for informing decisions on further evaluation in phase 2 trial but not for detection of any rare adverse events. Subsequent trials will allow assessment of any rare adverse events associated with vaccination. Long-term durability of the immune response could not be determined due to the short follow-up duration. In addition, the study participants were predominantly of white ethnicity, in a population where RVF is not endemic. The four visits conducted outside of the planned trial visit schedule may also have added variability to the measured immune responses. To generalise vaccine performance to populations at most risk, ChAdOx1 RVF and other candidate human RVF vaccines will need evaluation in the target populations in RVF-endemic regions and including adults, children and adolescents, who are all involved in animal husbandry, and in pregnant women where risk of RVF-associated miscarriage is high.