ChAdOx1 nCoV-19 vaccine does not protect against South African SARS-CoV-2 variant

Results of a randomized, double-blind, placebo-controlled trial conducted in South Africa show that the ChAdOx1 nCoV-19 (AZD1222) vaccine at Oxford has no efficacy against the B.1.351 variant in preventing mid-to-mid-term coronavirus infection 2019 (COVID-19), and showing fewer neutralizing properties of enhanced antibodies. The results are published in the New England Journal of Medicine.

The pace of development of vaccines against COVID-19 has been unparalleled, with six of them already authorized for emergency use. One of the most widely released is ChAdOx1 nCoV-19 (AZD1222) from the University of Oxford and AstraZeneca, which contains an atypical-deficient adenoviral vector from chimpanzee with severe respiratory coronavirus 2 (SARS-CoV-2) antigen series glycoprotein .

However, the virus rapidly developed mutations within the receptor binding domain (RBD) and N-terminal domain (NTD) of the glycoprotein spike, which are two main targets of the antibody response against SARS-CoV-2 induced by the vaccines.

Line B.1.1.7 (or N501Y.V1), first identified in the United Kingdom, induces N501Y mutation linked to increased binding of the virus to the angiotensin-converting enzyme receptor 2 (ACE2). , but also more referrals. for up to 53%.

In addition, line B.1.351 (N501Y.V2), first discovered in South Africa, harbors three RBD mutations and five supplemental NTD mutations. This is certainly a problem, as studies have shown that 48% of serum samples from convalescent donors infected with the prototype virus were unable to neutralize this mutated strain, as confirmed by assay neutralization spike-pseudovirus.

That is why this interim analysis, carried out by members of the Wits Group – VIDA COVID, aimed to address not only routine objectives for vaccine safety and efficacy but also efficacy correlations. are directed specifically against the viral variant B.1.351.

Setting up the test

To do so, this large research group conducted a randomized, double-blind, multicenter trial to test the AZD1222 vaccine in people who were not infected with the human immunodeficiency virus (HIV). ) in South Africa. The main criteria for absenteeism were the presence of HIV, previous or routine COVID-19, a history of vaccine-related anaphylaxis, and morbid obesity.

Selected participants were between 18 and 65 years of age and assigned to receive two doses of vaccine (in a 1: 1 ratio) containing either 5 × 10¹⁰ viral or placebo particles (containing saline or 0.9% sodium chloride solution) 21 to 35 days apart.

After the second dose, serum samples were taken from 25 participants and then tested with live virus and pseudovirus neutralization assays against the original viral restriction D614G and variant B.1.351. Safety and efficacy against simulated and laboratory COVID-19 were key completion points. In addition, Oxford University was responsible for overseeing the entire lawsuit.

Compromise neutralization response

In this interim report, both live virus and pseudovirus neutralization assessments showed greater resistance to the B.1.351 difference in serum samples from vaccine recipients compared to those from placebo recipients. Moderate to severe COVID-19 was observed in 3.2% of placebo recipients and 2.5% of vaccine recipients, representing an efficacy of 21.9%.

Nonetheless, both assay neutralization trials provide evidence that reduced or repeated antibody neutralization induced vaccination against the B.1.351 variant, similar to the responses seen in vaccine partners in the research efforts conducted in Brazil and the United Kingdom.

Although we do not yet know the degree of attenuation that may affect the effective neutral antibody response in humans, the highest level of neutralization against B.1.351 was in a person vaccinated with the live virus neutralization assay diluted 1:20, while the highest permanent titer against B.1.351 was less than 1: 200 in the pseudovirus neutralization assay.

Vaccination as a selection strain for SARS-CoV-2

An unanswered question mark after this trial is whether the boosted antibody response seen after a longer interval between the first and second doses of the active vaccine may neutral to provide a better residue against the South African variable compared to these results.

“Fighting human antibody responses is expected to become a feature of the coronavirus pandemic in the coming years, due to pressure on the virus to select for changes that may go unprotected after infection natural or immunized, ”study authors said. .

Finally, all considerations on the efficacy of the AZD1222 vaccine must be placed in the context of continued worldwide and community-wide distribution of the B.1.351 variant and the potential increase of strains. Another SARS-CoV-2 that induces similar mutations.