AstraZeneca Vaccine Preprint Does Not Bode Well for COVID-19 Variant Response

New preprint data suggest the AstraZeneca coronavirus 2019 (COVID-19) vaccine may not protect against mild-to-moderate infection due to the South Africa variant.

The to-be-reviewed research, from a team of South African institution investigators and the Oxford Vaccine Group, indicated the modified adenovirus-based vaccine ChAdOx1 nCoV-19 (AZD1222) had a vaccine efficacy of 21.9% (95% CI, -49.9 to 59.8) in protecting from COVID-19 more than 14 days after the booster dose was administered to seronegative patients, versus placebo.

In the 42 endpoint cases of COVID-19 detection, 15 mild cases and 4 moderate cases were observed in participants to receive both ChAdOx1 doses, versus 17 and 6 cases in placebo recipients, respectively.

Among the 41 primary endpoint cases sequenced and classified, 39 (95.1%) were B.1.351 variant infection.

This outcome observed among 700-plus study participants in South Africa is an approximate 54 percentage-point drop in vaccine efficacy previously observed in the same team’s research for the same vaccine—the key difference being that the more transmissible B.1.351 variant has been circulating South Africa during this most recent assessment.

What’s more, tests conducted to observe vaccine-induced antibody neutralization of the vaccine via pseudotyped (PSVNA) and live virus (LVNA) neutralization assays show its effect is lessened against the variant. In fact, the effect is similar to the observed loss of neutralizing activity induced by natural SARS-CoV-2 infection from the first wave versus the B.1.351 variant.

The currently available mRNA COVID-19 vaccines from Pfizer and BioNTech (BNT162b2) and Moderna (mRNA-1273) have had greater neutralizing antibody development after second doses than adenovirus-based vaccines including ChAdOx1 and Sputnik V, but have also been linked to PSVNA neutralization reductions versus B.1.351.

As of this weekend, South Africa's seven-day average for new daily COVID-19 cases was just under 2400. A month prior, it was above 18,000, due to the variant.

Vaccine developers are undergoing feasible efforts to augment prophylaxes in response to such variants spreading more greatly—and as the AstraZeneca investigators noted, differing vaccine products have shown capability to fare differently against unique variants. And what’s more, the team continued to observe vaccine benefit against severe COVID-19, defined as death or hospitalization due to infection, regardless of the variant.

But the findings are a nonetheless troublesome development for a vaccine anticipated to be manufactured at a rate of 3 billion doses this year, at costs lesser than other COVID-19 vaccines.

“Deliberations on the utility of ChAdOx1 nCoV-19 also needs to be considered in the context of ongoing global spread and community transmission of the B.1.351 variant, and evolution of other SARS-CoV-2 lineages that include similar mutations,” investigators wrote.

Last week, on the eve of this preprint data becoming available, South Africa health and legislative authorities announced plans to delay administration of ChAdOx1 nCov-19 to its healthcare workers, as previously planned, and instead immunize them with the single-shot Johnson & Johnson vaccine.

The Johnson & Johnson product Ad26.COV2.S is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike (S) protein. Based on preliminary phase 3 findings, the US Food and Drug Administration (FDA) recently accepted the company’s Emergency Use Authorization (EUA) application and set a Vaccines and Related Biologic Products Advisory Committee (VRBPAC) meeting to review its benefit-risk profile on February 26.

In speaking with Contagion® on the matter of the new ChAdOx1 findings, expert vaccinologists stressed the utility of the vaccine in reducing severe COVID-19 disease and hospitalizations. That said, they estimated alteration to the vaccine to appropriate respond to the South Africa variant would take another 6 months, and in the meantime, mRNA platform-based vaccines may be more suitable to respond to more transmissible variants than adenovirus-based vector platforms including ChAdOx1 and Ad26.COV2.S.