South African and Brazilian SARS-CoV-2 variants can evade antibodies from therapies, vaccines, and infection

By Angela Betsaida B. Laguipo, BSNApr 7 2021

Coronavirus disease 2019 (2019) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen. Over a year into the COVID-19 pandemic, new variants of concern have emerged and posed serious health threats globally. These new variants have exhibited heightened transmissibility and immunity evasion potential.

In a new study, published in the journal Cell, researchers in Germany found that the variants B.1.1.7 (or United Kingdom) variant, the B.1.351 (or South African) variant, and the P.1 (or Brazilian) variant do not show augmented host cell entry.

The team also found that the B.1.351 and P.1 variants have the potential to evade therapeutic antibodies or antibodies induced by natural infection or vaccination.

Study: SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies. Image Credit: Dana.S / Shutterstock

SARS-CoV-2 variants of concern

In the U.K., the B.1.1.7 variant emerged with multiple mutations at the spike glycoprotein, including the N50Y1 mutation; the 69/70 deletion; the E484K, which may affect neutralization by some monoclonal antibodies; and the P681H, near the S1/S2 furin cleavage site.  It was first reported in December 2020, and since then, it has reached many countries.

Recent studies have shown that this variant spreads faster and may even increase the risk of death.

Meanwhile, another variant emerged in South Africa, known as B.1.351. This variant shares some mutations with the B.1.1.7 variant, including the E484K and the N501Y.

The P.1 variant emerged in Brazilian tourists tested in Japan. The variant has 17 unique mutations, including three in the receptor-binding domain (RBD) of the viral spike protein.

It is unclear whether antibody responses in convalescent patients protect against re-infection with the new variants.

The study

In the study, the team examined how the S proteins of the B.1.1.7, B.1.351, and the P.1 variants drive fusion with human cells. They found that the S protein failed to mediate fusion with target cells, expressing only angiotensin-converting enzyme 2 (ACE2), but successfully drove fusion with cells co-expressing ACE2 and TMPRSS2. The access can thus be blocked by soluble ACE2 protease inhibitors active against the TMPRSS2, and membrane fusion inhibitors.

The team also demonstrated that monoclonal antibodies with emergency use authorization (EUA) for COVID-19 treatment partially or completely failed to inhibit entry driven by the S proteins of the B.1.351 and the P.1 variants.

Even though host cell interactions that underlie viral entry might not differ significantly between the SARS-CoV-2 Washington isolate, major differences in vulnerability to antibody-mediated neutralization were observed.

The study showed that entry drive by the S proteins of the B.1.351 and P.1 variants was only partially inhibited by Casirivimab. Meanwhile, combining Casirivimab and Imdevimab within an antibody cocktail with EUA (REGN-COV2) restored effective inhibition. This means that REGN-COV2 may help in treating COVID-19 patients.

Moreover, the variants were less effectively inhibited by convalescent plasma and sera from people who were vaccinated with the BNT162b2 COVID-19 vaccine.

The team suggested that the variants B.1.351 and P.1 are resistant to neutralizing antibodies. They evade inhibition by neutralizing antibodies, which could pose a threat amid the global health efforts for vaccination rollouts.

The researchers noted that the entry driven by the S protein of the B.1.1.7 could be efficiently inhibited by antibodies induced during infection and vaccination. Past studies have also shown that BNT162b2-vaccinated individuals developed antibodies that can efficiently neutralize the virus.

Our findings indicate that the B.1.351 and P.1 variants might be able to spread in convalescent patients or BNT162b2-vaccinated individuals and thus constitute an elevated threat to human health,” the team concluded.

The COVID-19 pandemic has now affected 192 countries and regions. Over 131.96 million people have been infected with SARS-CoV-2, which has resulted in over 2.86 million deaths.