The recombinant adenovirus vector vaccine, ChAdOx1, against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was found to be safe and efficacious during 4 blinded, randomized, controlled trials conducted in the United Kingdom (UK), Brazil, and South Africa. The result were published in The Lancet.1

The ChAdOx1 vaccine was produced by a collaboration between AstraZeneca and Oxford University as a not-for-profit product aiming for the equitable supply for low- and middle-income countries. It was developed on the basis of existing vaccine technology and may easily be incorporated into the established vaccine distribution networks without requiring specialized storage equipment needed by the 2 new mRNA vaccines recently distributed by Pfizer and Moderna.2,3 mRNA vaccines will also be priced significantly higher compared to the ChAdOx1 vaccine.4

“Just think about the expense to the WHO of purchasing, shipping, and distributing the mRNA vaccines,” Dr Maria Knoll, senior scientist at the Global Disease Epidemiology and Control division at Johns Hopkins Bloomberg School of Public Health, and coauthor of a commentary published alongside this interim analysis.4 “With this less expensive vaccine, we can devote our financial and mental resources to solving some other problem and not that one.”


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ChAdOx1 Clinical Trial Design

South Africa

  • Phase 1/2 trial; single-blind
  • 2096 participants with or without HIV aged 18 to 65
  • Treatment group: Half-dose (unspecified viral particles)) followed by standard dose (3.5-6.5×10¹⁰ viral particles); 2 standard doses (3.5-6.5×10¹⁰ viral particles)
  • Control group: unspecified

United Kingdom

  • Phase 1/2 trial; single-blind
  • 1077 participants aged 18 to 55 years
  • Treatment group: 2 standard doses (5×10¹⁰ viral particles)
  • Control group: meningococcal group A, C, W, and Y conjugate vaccine

United Kingdom

  • Phase 2/3 trial
  • 10,673 participants aged 18 years or older; priority for high-exposure professions
  • Treatment group: low-dose (2.2×10¹⁰ viral particles) followed by standard dose (5×10¹⁰ viral particles); 2 standard doses (5×10¹⁰ viral particles)
  • Control group: meningococcal group A, C, W, and Y conjugate vaccine

Brazil

  • Phase 3, single-blinded
  • 10,002 participants aged 18 or older; priority for high-exposure professions
  • Treatment group: 2 doses (3.5-6.5×10¹⁰ viral particles), unspecified if standard or half-dose
  • Control group: meningococcal group A, C, W, and Y conjugate vaccine

All trials aimed to administer the second dose at 4 weeks, but some participants received theirs as distant as 12 weeks.

Results

Across the 4 trials (N=11,636), 5807 participants received 2 doses of the AstraZeneca vaccine and 5829 participants received placebo.

Among participants who received 2 doses of active vaccine, the overall vaccine efficacy was 70.4% (95% CI, 54.8%-80.6%). Stratified by dose, 2 standard doses had an efficacy of 62.1% (95% CI, 41.0%-75.7%), and low-dose followed by standard-dose had an efficacy of 90.0% (95% CI, 67.4%-97.0%).

By day 21 after receiving the first dose of active vaccine, a total of 10 participants were admitted to the hospital for SARS-CoV-2. All of these participants received the control, indicating a high efficacy for protection against severe illness.

The phase 2/3 trial conducted in the United Kingdom was designed to assess the possibility of asymptomatic spread of SARS-CoV-2 through vaccinated individuals. Each participant self-administered nose or throat swabs every week. Asymptomatic infections were detected among 29 participants (0.9%) in the vaccine group and 40 participants (1.2%) in the control group, indicating an efficacy of 27.3% (95% CI, -17.2% to 54.9%) against asymptomatic SARS-CoV-2.

Serious adverse events were observed among 79 participants in the vaccine group and 89 participants in the control group. Serious events determined to be possibly related with ChAdOx1 included hemolytic anemia, transverse myelitis, and fever over 40°C.

Implications for Public Health

Compared with recently published interim results from other vaccine products, the efficacy rates of ChAdOx1 were lower than the mRNA vaccine, BNT162b2, produced by Pfizer and BioNTech (95%; 95% CI, 90.3%-97.6%) or mRNA-1273, produced by Moderna (94.1%; 95% CI, 89.3%-96.8%).2,3 It was, however, more comparable with the other adenovirus vector vaccine, Ad26.COV2.S, from Johnson & Johnson which reported T-cell responses among over 60% of participants.5

When asked about how important the differences in efficacy are among these vaccine products, Dr. Knoll emphasized that “these differences have little public health consequences – meaning they’re all good enough. The smallpox vaccine, for example, was only 80% effective, and we eliminated smallpox. They don’t have to be perfect for them to be effective.”

With several effective vaccine options available, after ensuring wide distribution of these products, perhaps the next important step is to assess performance against new coronavirus variants. “We should expect many new variants to be identified during 2021,” commented Stephen Rouse, Head of University Communications at Oxford University. “The University of Oxford is carefully assessing the impact of new variants on vaccine immunity and evaluating the processes needed for rapid development of adjusted COVID-19 vaccines if these should be necessary.”

Variant Coverage

In light of new concerns surrounding variants, the Oxford Vaccine Group has submitted a study to the Lancet, which has not yet been peer-reviewed. This preprint, an analysis on the efficacy of ChAdOx1 on variant B.1.1.7, was posted on February 4, 2021.6

Study authors concluded that the “Efficacy of ChAdOx1 nCoV-19 against the B.1.1.7 variant of SARS-CoV-2 is similar to the efficacy of the vaccine against other lineages.”

Wits Vaccines and Infectious Diseases Analytics Research Unit, which runs the Oxford COVID-19 vaccine trial in South Africa, also submitted a preprint for peer-review publication. This preprint, an analysis on the vaccine’s efficacy against variant B.1.351, was posted in early February, 2021, and a summary of trial results was published by the University of Witwatersrand, Johannesburg, on February 7, 2021.7

Investigators concluded that “a 2-dose regimen of the ChAdOx1 nCoV-19 vaccine provides minimal protection against mild-moderate COVID-19 infection from the B.1.351 coronavirus variant.”

Conclusions

The high efficacy and satisfactory safety profile of the ChAdOx1 vaccine coupled with its low cost and simplified storage requirements make this vaccine a promising candidate for providing protection against SARS-CoV-2 for a more broad population, especially among those living in lower-income countries or rural areas.

Stephen Rouse concluded, “We’re going to need a range of vaccines, and in due course we’ll know which vaccines are most effective for different ages, and populations. Our vaccine can be deployed quickly in existing health settings, which will help to stop the further spread of this disease and save lives while we learn more and more about how to prevent and treat it.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

1. Voysey M, Clemens S A C, Madhi S A, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021;397(10269):99-111. doi:10.1016/S0140-6736(20)32661-1.

2. Polack F P, Thomas S J, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020;383(27):2603-2615. doi:10.1056/NEJMoa2034577.

3. Baden L R, El Sahly H M, Essink B, et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2020;NEJMoa2035389. doi:10.1056/NEJMoa2035389.

4. Knoll M D, Wonodi C. Oxford-AstraZeneca COVID-19 vaccine efficacy. Lancet. 2021;397(10269):72-74. doi:10.1016/S0140-6736(20)32623-4.

5. Sadoff J, Le Gars M, Shukarev G, et al. Interim Results of a Phase 1–2a Trial of Ad26.COV2.S Covid-19 Vaccine. N Engl J Med. 2021;NEJMoa2034201. doi:10.1056/NEJMoa2034201.

6. Emary KRW, Golubchik T, Aley PR, et al; for the Oxford Vaccine Group. Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 VOC 202012/01 (B.1.1.7). Lancet. Posted online February 4, 2021. doi:10.2139/ssrn.3779160 https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3779160

7. Oxford COVID-19 vaccine trial results. University Of The Witwatersrand, Johannesburg. February 7, 2021. Accessed February 10, 2021. https://www.wits.ac.za/covid19/covid19-news/latest/oxford-covid-19-vaccine-trial-results.html

This article originally appeared on Infectious Disease Advisor