News release

From: Springer Nature

STUDY 1 Immunology: The SARS-CoV-2 501Y.V2 variant escapes neutralization by some COVID-19 donor plasma and antibodies

A laboratory-developed pseudovirus containing the mutations found in the SARS-CoV-2 501Y.V2 variant (first detected in South Africa) was resistant to neutralization when exposed to three types of COVID-19 therapeutic antibodies or convalescent plasma, according to a paper published in Nature Medicine. These findings raise the possibility of reinfection and suggest that vaccines that target the SARS-CoV-2 spike may not be as effective against emerging variants of the virus.

People infected with SARS-CoV-2 develop neutralizing antibodies that can persist for months and can protect a person from reinfection. These antibodies are also being pursued as potential therapeutic treatments for the virus. However, whether antibodies to SARS-CoV-2 can neutralize new variant strains has remained unclear.

Penny Moore and colleagues used a pseudovirus neutralization assay — a laboratory-generated single entry virus routinely used for such assays — that contained the mutations found in the viral spike protein of the SARS-CoV-2 501Y.V2 variant. They then compared neutralization of 501Y.V and the original lineage by three classes of antibodies and found that all three classes of antibodies neutralized the original lineage but not the 501Y.V2 variant. Next, the authors tested neutralization by convalescent plasma derived from 44 patients, including people hospitalized with severe COVID-19. There was a substantial loss of neutralizing activity in the samples assessed against the 501Y.V2 variant, and nearly half of the samples showed no detectable neutralization activity. Only three samples — from patients with severe symptoms — showed high levels of neutralization activity. Despite the lack of neutralization, these antibodies still bound to the variant spike, which suggests that they may help to provide protection in a different way.

Although further research is needed, these findings demonstrate the urgent demand for rapidly adaptable vaccine design platforms, and the need to identify more-stable viral targets to incorporate into future therapies, argue the authors.

STUDY 2 Immunology: New variants show resistance to antibody neutralization

Some of the newer SARS-CoV-2 variants show resistance to the effect of neutralizing antibodies in laboratory experiments, according to a paper published in Nature Medicine. This finding may have implications for vaccine design and for the use of antibody therapies to treat COVID-19.

Neutralizing antibodies block the ability of viruses to enter host cells. They are produced by the body in response to both infection and vaccination and are important because they help to generate long-term immunity. However, whether antibodies to SARS-CoV-2 can also neutralize new variants of the virus remains unclear.

Michael Diamond, Pei-Yong Shi, Ali Ellebedy and colleagues assessed the ability of antibodies to neutralize some of the newer SARS-CoV-2 lineages, such as the United Kingdom variant (B.1.1.7), as well as genetically engineered chimeric viruses containing the spike proteins of South African (B.1.351) and Brazilian (B.1.1.248) variants, such as the Washington strain of SARS-CoV-2 (Wash SA-B.1.351).

The authors collected monoclonal antibodies and samples of serum (which contains neutralizing antibodies) from convalescent patients with COVID-19 and people who received the Pfizer–BioNTech vaccine, and then tested their neutralizing ability against a panel of naturally occurring SARS-CoV-2 variants and synthetic SARS-CoV-2 variants created in the laboratory. Most samples showed reduced inhibitory activity against viruses with the B.1.351 spike protein or other SARS-CoV-2 viruses that contained mutations at positions 484 and 501. This finding suggests that the current neutralizing antibodies may have less efficacy against the South African variants or other viruses with mutations at both 484 and 501.

The findings may have therapeutic implications, as immune plasma from people infected early during the pandemic might fail to protect patients infected with some of the newer strains. Adjustments may need to made to some of the existing therapeutic antibody cocktails, as well as vaccine sequences, but the authors caution that corroborative case studies in patients are needed to back up their findings.