By Mariana Bego

Variant first identified in South Africa not so easily neutralized by non-specific antibodies

A multi-centered French group, led by Dr. Olivier Schwartz at the Pasteur Institute of Paris, examined how antibodies from previously infected and vaccinated individuals responded to two of the SARS-CoV-2 variants of concern, those first identified in the United Kingdom (B.1.1.7) and South Africa (B.1.351).

Samples from individuals who recovered from COVID-19 neutralized the parental virus (D614G) in similar way to the variant first identified in the United Kingdom (B.1.1.7), but only if the samples were collected within the first nine months after symptoms. Samples collected after this window had a significant reduction in the amounts of neutralizing antibodies to both the parental virus and variants B.1.1.7. The variant first identified in South Africa (B.1.351), was more resistant to neutralization from sera collected at all time points. Additionally, 40% of the samples collected nine months after symptoms completely lost their effectiveness against this variant.

The authors also analyzed samples from individuals who received both doses of the Pfizer mRNA vaccine, and observed similar trends. The neutralization capacity of the post-vaccine sera had similar potency against D614G and B.1.1.7, but they were less efficacious against B.1.351. The authors suggest the variant first identified in South Africa (B.1.351), but not the variant first identified in the United Kingdom (B.1.1.7), may increase the risk of infection in immunized individuals. These results were published at the end of March in Nature Medicine.

 

Bispecific antibodies neutralize better and are more difficult to evade

Antibodies are often drawn as capital letter Y. They naturally have two identical binding sites, one at each end of the upper arms of the Y. But antibodies can be engineered in the laboratory to bind to two different targets. These are called bispecific antibodies. European and American scientists, led by Dr. Luca Varani of Università della Svizzera Italiana in Switzerland, developed bispecific antibodies capable of neutralizing the three currently circulating SARS-CoV-2 variants of concern, those first identified in the United Kingdom (B.1.1.7), South Africa (B.1.351) and Brazil (P.1 or B.1.1.28.1). Neutralization for B.1.351 was the lowest among the variants tested.

Antibodies have been approved in many countries, including Canada, for the treatment of mild to moderate COVID-19 in patients who are at high risk of progressing to severe disease. But some antibody treatments could push the virus to evolve and generate what is known as escape mutants, a new form of the virus that is not resistant to that antibody. The original two antibodies used to generate the bispecific antibody selected in this manuscript generated SARS-CoV-2 escape mutants when used individually. But the team proved that these escape mutants were now neutralized by the bispecific antibody.

The authors used a novel animal model in order to test if SARS-CoV-2 could escape neutralization from bispecific antibodies. In their model of SARS-CoV-2 infection, the bispecific antibodies protected mice from disease and suppressed viral escape. The authors suggested that the use of bispecific antibodies is feasible and effective, combining the advantages of antibody cocktails into a single molecule.

These results were published in Nature, as an accelerated article preview available online at the end of March.

 

People infected with variant first identified in South Africa have cross-reactive antibodies

South Africa’s first wave of coronavirus infections peaked in July 2020, and the second peaked in January 2021. Most of the cases of the second wave were due to the B.1.351 variant. As in the report cited above and several others, this variant was shown to be partially resistant to antibodies formed by previously circulating variants, leading to concerns that current vaccines may not be effective against it.

To address these concerns, Tulio de Oliveira and Alex Sigal from University of KwaZulu-Natal in South Africa and their colleagues tested plasma from people who had been infected during these two waves. Their team found that plasma from donors infected in the second wave was 15 times more effective at preventing the B.1.351 variant from infecting cells in a laboratory dish, compared with plasma from donors infected in the first wave. They also reported that antibodies from people infected with the B.1.351 coronavirus variant are also effective against previously circulating variants, suggesting that updated vaccines against this variant might work against a range of coronavirus variants.

These results were published on the March, 29th edition of Nature.