How resistant is the SARS-CoV-2 Brazilian variant to antibodies?

By Michael BurgessMar 18 2021

Researchers based at the University of Oxford, UK, and the Instituto Leônidas e Maria Deane, Brazil, have shown that the P.1 Brazilian variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is less resistant to natural or vaccine acquired antibody responses than the B.1.351, South African, variant, despite sharing convergent mutations.

A pre-print version of the research paper is available to read in full on the bioRxiv*server.

Study: Antibody evasion by the Brazilian P.1 strain of SARS-CoV-2. Image Credit: ktsdesign / Shutterstock

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

The coronavirus disease 2019 (COVID-19) pandemic continues to permeate across the globe. Due to its rapid spread and replication rate since its first identification in Wuhan, China, in December 2019, the virus has given rise to multiple variant strains. Some of these variants have acquired mutations that increase transmissibility and potential resistance to current vaccine and antibody therapies.

There are three variants considered to be of primary concern at present: the South African (B.1.351), UK (B.1.1.7) and Brazil (P.1) variants.

P.1 was first identified in Manaus, Brazil, in early January 2021, and convergently shares a number of mutations with the other two variants associated with increased transmissibility and antibody resistance.

The researchers investigated and described the antibody evasion potential of the P.1 variant of COVID-19 (caused by SARS-CoV-2).

P.1 background

P.1 has three main substitutions on the spike (S) protein of the receptor-binding domain (RBD) region of the virus. K417T and E484K have been evidenced in previous studies to promote antibody resistance, and the N501Y mutation is thought to increase binding affinity to the angiotensin-converting enzyme 2 (ACE2), which is how SARS-CoV-2 enters and infects host cells. Both the South African and UK variants have this N501Y mutation, but the former also contains a K417N and E484K mutation.

The study

The research team tested the effectiveness of convalescent blood sera against the P.1 variant, as well as the effectiveness of the Oxford-AstraZenca and Pfizer-BioNTech vaccines. Immune evasion responses to these were also compared to that of the original Wuhan strain, and the South African and UK strains of SARS-CoV-2.

The team observed that P.1 could fully escape neutralization from a large number of common antibodies found in convalescent plasma that are effective against the ancestral virus. A similar reduction in effectiveness was also observed in the B.1.1.7 and B.1.351 variants, although the latter showed greater immunity than the former two.

The researchers also demonstrated that P.1 had greater ACE2-RBD binding efficacy than the ancestral model, but describe how one monoclonal antibody, mAb 222, was especially potent against the variant.

mAb 222 contacts both the K417 and N501 regions of the virus, and resists the mutations found in the P.1 and B.1.351 viruses in that region (501Y and 417T/N, respectively). The team found that this is possible due to the light chain of the antibody.

Antibodies are comprised of two immunoglobulin heavy chains and a single light chain. The two heavy chains define the class of the antibody, and act as the binders to antigens. The light chain subunit connects the two heavy chains. The research team restored the neutralizing ability of certain antibodies by swapping the light chain with the one present on mAb 222.

What are the implications?

The researchers report that P.1 resists many antibodies associated with ancestral SARS-CoV-2 immunity, although it has a lower degree of resistance than B.1.351. Monoclonal antibody 222 neutralizes all three variants of concern, and the light chain of 222 can restore the neutralizing ability of SARS-CoV-2 antibodies for mutated strains of the virus.

The restoration of antibody effectiveness has broad implications for current vaccine programs; it may allow for effective vaccine boosters for all three variants mentioned here, and potentially any future variants that may arise in the future with antibody-resistant mutations.

The authors caution that their investigation fails to account for the effectiveness of antibody-dependent cell-mediated cytotoxicity, which may affect neutralization of the virus in vivo – this experiment was all performed in vitro. However, the team encourages further investigation of cross-protective measures against multiple COVID strains.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources