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Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 VOC 202012/01 (B.1.1.7)

Our take —

Clinical efficacy of the ChAdOx1 nCoV-19 vaccine (Oxford/AstraZeneca) preventing symptomatic COVID-19 was similar between the UK variant (B.1.1.7) and other viral lineages even though the vaccine induced neutralizing antibodies were less effective against the B.1.1.7 variant. This suggests that a lower level of neutralizing antibodies may be needed to prevent symptomatic infection than previously thought, and/or other immune mechanisms may contribute to protection. Results also suggested that vaccine recipients appear less likely to transmit virus compared to unvaccinated individuals. Overall, these data support the ongoing use of this vaccine in areas that contain variant B.1.1.7 or the original strain.

Study design

Randomized Controlled Trial

Study population and setting

This study used samples collected from participants in a phase II/III trial testing the safety and efficacy of the ChAdOx1 nCoV-19 vaccine (Oxford/AstraZeneca) in adults age 18 years and older at 20 centers across the UK. Symptomatic patients had nasopharyngeal and oral swabs taken, while all patients provided a weekly self-administered nose and throat swab for NAAT testing beginning 1 week after their first vaccination. Samples were processed by nucleic acid amplification testing (NAAT). Cases were excluded if they came up positive before 15 days post-second vaccination. PCR cycle threshold (Ct) values served as a proxy for measuring viral load (lower values equate to higher viral loads). Positive samples were sequenced (SARS-CoV-2 in samples) and viral lineages were assigned. Sera from vaccinated participants was tested for neutralization against the UK variant (B.1.1.7) and a canonical non-B.1.1.7 Victoria lineage from Australia.

Summary of Main Findings

Out of 499 participants that developed COVID-19 between October 1, 2020 and January 14, 2021, investigators were able to obtain sequences from 256 participants (a total of 322 swabs). Of these, 179 were in the primary efficacy cohort (120 symptomatic, 44 were asymptomatic/unknown, and 15 “other”). About 2/3 of infections were due to non-UK lineages while about 1/3 were caused by the UK variant (B.1.1.7). Overall vaccine efficacy against the B.1.1.7 variant was lower but similar to that against other variants (66.5% vs. 80.7%, respectively). Symptomatic cases had a higher viral load compared to asymptomatic cases and were PCR positive for a longer time period, with vaccination reducing that length of time by 1 week. The length of time participants tested positive for virus did not differ between the UK variant and other variants. Participants in the vaccinated group exhibited lower viral loads compared to those in the control group. Neutralizing antibody titers were 9 times lower  (i.e., less effective) against the UK lineage compared to the Victoria lineage of the SARS-CoV-2 virus.

Study Strengths

Swabs were collected from patients at several time points in order to track viral load over time, and sequencing was performed in order to determine viral lineages in actual COVID-19 cases. Clinical efficacy was tested in participants who had received varying vaccine dosing strategies. Viral load in addition to neutralizing antibody efficacy were studied.

Limitations

New viral variants are beginning to appear as the virus begins to evolve within the population. Additionally, positive PCR results may not truly indicate live, transmissible virus, and a true correlate of immune protection has still not been established. Samples with Ct values greater than 30 were not sequenced, so the lineages of virus in patients with low viral load were unable to be assessed. Additionally, sequences from all positive swab samples were unable to be obtained due to logistical constraints. Finally, false positive samples could not be sequenced since they did not contain virus, and therefore fell into a category of negative clinical efficacy, possibly skewing results.

Value added

This study provides the first data on clinical efficacy of the ChAdOx1 nCoV-19 vaccine against the UK variant of SARS-CoV-2 compared to other lineages.

This review was posted on: 19 February 2021