Efficacy of ChAdOx1 nCoV-19 Vaccine Against B.1.1.7 Variant

Apr 05, 2021
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Authors:
Emary KR, Golubchik T, Aley PK, et al., on behalf of the COVID-19 Genomics UK Consortium, the AMPHEUS Project, and the Oxford COVID-19 Vaccine Trial Group.
Citation:
Efficacy of ChAdOx1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 Variant of Concern 202012/01 (B.1.1.7): An Exploratory Analysis of a Randomized Controlled Trial. Lancet 2021;Mar 30:[Epub ahead of print].
Summary By:
Salim Hayek, MD, FACC

Quick Takes

  • The B.1.1.7 variant of SARS-CoV-2 is associated with higher viral loads and increased risk of transmission compared to non-B.1.1.7 variants.
  • This study is a post hoc in vitro and in vivo efficacy analysis of the Oxford/AstraZeneca ChAdOx1 vaccine using data from the UK COV002 phase 2/3 trial.
  • In vitro neutralization activity against the B.1.1.7 variant using sera from vaccinated participants appeared to be reduced compared to non-B.1.1.7 variants, but clinical efficacy of the ChAdOx1 was similar in preventing symptomatic COVID-19 due to both variants.

Study Questions:

Is the Oxford/AstraZeneca ChAdOx1 vaccine effective against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 variant?

Methods:

This study reports the results of an in vitro analysis of vaccine-induced neutralizing antibody responses against B.1.1.7, and a post hoc analysis of the clinical efficacy of ChAdOx1 nCoV-19 against disease caused by the B.1.1.7 variant of concern, using data from the UK COV002 phase 2/3 trial assessing the safety and efficacy of the ChAdOx1 nCoV-19 vaccine. Adults enrolled in the trial (n = 8,534) provided weekly self-collected nose and throat swabs for SARS-CoV-2 nucleic acid testing and subsequent sequencing. Immunogenicity was tested in vitro using sera from vaccinated participants and the B.1.1.7 lineage and a canonical non-B.1.1.7 viral lineages (BetaCoV/Australia/VIC01/2020). The primary outcome was symptomatic coronavirus disease 2019 (COVID-19) disease, defined as a positive nuclear acid test result on an upper airway swab in a participant with at least one symptom.

Results:

Of 8,534 participants in the primary efficacy cohort, 6,636 (78%) were aged 18–55 years and 5,065 (59%) were female. Between October 1, 2020, and January 14, 2021, 520 participants developed SARS-CoV-2 infection. 1,466 nucleic acid amplification test (NAAT)-positive nose and throat swabs were collected from these participants during the trial. Of these, 401 swabs from 311 participants were successfully sequenced. Among symptomatic cases, 52 (35%) of 147 were due to the B.1.1.7 variant and 95 (65%) were caused by non-B.1.1.7 lineages. Laboratory virus neutralization activity by vaccine-induced antibodies was lower against the B.1.1.7 variant than against non-B.1.1.7 lineage (geometric mean ratio, 8.9; 95% confidence interval [CI], 7.2–11.0). Clinical vaccine efficacy against symptomatic NAAT-positive infection was 70.4% (95% CI, 43.6–84.5) for B.1.1.7 and 81.5% (95% CI, 67.9–89.4) for non-B.1.1.7 lineages. None of the participants were hospitalized or died due to COVID-19.

Conclusions:

In vitro ChAdOx1 nCoV-19 showed reduced neutralization activity against the B.1.1.7 variant compared with a non-B.1.1.7 variant; however, clinical efficacy of the vaccine was similar against the B.1.1.7 and non-B.1.1.7 variants of SARS-CoV-2.

Perspective:

This study adds to the mounting evidence of vaccine effectiveness against the different variants of SARS-CoV-2. The B.1.1.7 SARS-CoV-2 variant first identified in the UK in late 2020 has 23 mutations across the viral genome; significantly more than other lineages. Some of these mutations of the spike protein coding region have been shown to increase ACE2 receptor binding affinity and viral escape in immunocompromised individuals. At the time the B.1.1.7 was identified, population immunity to the natural infection was low, and vaccine programs had not been initiated. Thus, the rapid spread of the variant is likely due to its improved affinity to the ACE2 receptor rather than the result of vaccine-induced immunity, and does not represent a “resistant” strain. Neutralizing antibodies to SARS-CoV-2 may target various epitopes in different areas of the spike protein and could provide protein against infection even in the presence of different mutations. The fears surrounding the spread of novel SARS-CoV-2 variants and their resistance to current vaccines are so far not validated. Vaccination remains the only viable solution to end this pandemic.

Clinical Topics: COVID-19 Hub, Prevention

Keywords: Antibodies, Neutralizing, Antibodies, Viral, Coronavirus, COVID-19, Genome, Viral, Mutation, Nucleic Acid Amplification Techniques, Peptidyl-Dipeptidase A, Primary Prevention, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Vaccines


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