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Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial

Our take —

This Phase 1, comparator-vaccine controlled study provides encouraging preliminary evidence that the ChAdOx1 nCoV-19 vaccine candidate is well tolerated and elicits an immune response at least comparable to antibody levels observed in a panel of convalescent plasma. This study suggests that a single dose of this vaccine candidate could be effective, but more data is needed regarding a prime-boost regime. This is a Phase 1 study, and as such is done with limited participant numbers. Larger Phase 2 and Phase 3 trials are still required to fully evaluate the efficacy of this vaccine candidate. Additionally, continued monitoring of participants will be done to evaluate safety and immune response over time.

Study design

Randomized Controlled Trial

Study population and setting

Phase 1/2 single blinded, comparator-vaccine controlled, randomized control trial performed in the UK to test the safety and immunogenicity of the chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein. Healthy adults (1077 enrolled) age 18–55 years received a single dose of the virus or comparator control. A group of ten participants were assigned to a non-randomized, unblinded prime-boost group receiving the booster dose at 28 days after the initial dose.

Summary of Main Findings

No serious adverse events were reported. Systemic and adverse events (including pain, feeling feverish, chills, muscle ache, headache, and malaise) were more common in the CHAdOx1 nCoV-19 group, and were mostly mild or moderate and all self-limiting. Antibody responses to the spike protein were maximal at day 28 in the single dose group and increased by day 35 in the 2-dose group. Observed serum antibody levels were similar to those in a panel of convalescent serum. Neutralizing antibody responses against SARS-CoV-2 were also detected in the single and 2-dose groups.

Study Strengths

This study was controlled with a comparator vaccine and monitored appropriate markers for safety and tolerability. Comparison of antibody titers to levels in convalescent serum is helpful for understanding the magnitude of the immune response elicited by the vaccine candidate.

Limitations

There is no known correlate of protection for SARS-CoV-2 infection. While comparisons to convalescent plasma are informative, it is still unknown what types and magnitude of immune response is required for protection against SARS-CoV-2 infection. No data regarding T-cell response is reported here. Continued monitoring of participants will be necessary and is ongoing to understand the safety and durability of the immune response. This trial only included participants as old as 55 years of age, and the study population was not ethnically diverse. The results from safety and immunogenicity studies in more diverse populations and in populations 55 years and older will be required and are on-going. Additionally, the prime-boost group was very small and will need to be expanded to understand any possible benefit of a prime-boost regimen.

Value added

This study provides encouraging preliminary evidence that the ChAdOx1 nCoV-19 vaccine candidate is well tolerated and elicits an immune response at least comparable to antibody levels observed in a panel of convalescent plasma.

This review was posted on: 24 July 2020