SARS-CoV-2 variants from South Africa and Brazil show resistance to therapeutic antibodies
A team of scientists from Germany tested the effectiveness of the therapeutics currently in use in treating newer variants of Coronavirus 2 (SARS-CoV-2) with severe acute respiratory syndrome, including B.1.1.7 (UK), B.1.351 (South Africa) , determined) and B.1.1.248 (Brazil) variants. Their results show that both variants B.1.351 and B.1.1.248 can escape humoral immune responses that are provoked by therapeutic antibodies, vaccinations or natural SARS-CoV-2 infections. The study is currently available on the bioRxiv * preprint server.
Since its emergence in December 2019, the highly infectious and deadly SARS-CoV-2, the causative agent of the 2019 coronavirus disease (COVID-19), has infected more than 108 million people and claimed more than 2.3 million lives worldwide. In a global effort to control the spread of viruses, many studies have been conducted in search of effective therapeutic strategies against COVID-19. Several reused antiviral drugs and therapeutic antibodies are currently being used to treat critical COVID-19 patients. As a protective measure, some potential vaccines against the viral spike protein have received emergency approval from the concerned authorities.
In the later phase of the pandemic, several new variants of SARS-CoV-2 were developed, including variants B.1.1.7 (UK), B.1.351 (South Africa) and B.1.1.248 (Brazil). Several mutations found in the spike protein of these variants were found to significantly increase their infectivity. In addition, there are preliminary studies to suggest that these variants may be more virulent and likely to increase the COVID-19-related mortality rate. With the majority of currently available therapeutic antibodies and vaccines primarily targeting the SARS-CoV-2 spike protein, potential concerns arise about the effectiveness of current therapeutic interventions in preventing the spread and lethality of newly emerged variants.
In the current study, scientists looked at the effectiveness of virus entry inhibitors, monoclonal antibodies, and vaccines in preventing infections from SARS-CoV-2 variants from the UK, South Africa and Brazil.
Scientists used both human and animal cell lines to conduct in vitro experiments. To analyze the effectiveness of virus entry inhibitors against the SARS-CoV-2 variants, they used soluble angiotensin converting enzyme 2 (ACE2), cellular protease inhibitors (TMPRSS2), and membrane fusion inhibitors (EK1 and EK1C4). To determine whether these variants are resistant to host humoral immune responses, the scientists thoroughly analyzed the effectiveness of anti-SARS-CoV-2 antibodies obtained from three different types of sources: 1) therapeutic monoclonal antibodies (casirivimab, imdevimab and Bamlanivimab); 2) plasma samples from critically ill COVID-19 patients; and 3) serum samples from subjects vaccinated with BioNTech / Pfizer vaccine (BNT162b2).
Although there is evidence of increased transferability of recently emerged SARS-CoV-2 variants, the scientists in the current study did not observe any significant differences in the dynamics of host cell entry between the wild-type virus and the variants Great Britain, South Africa and Brazil. In particular, the wild-type spike proteins and all tested variants of SARS-CoV-2 showed a comparable efficiency when entering host cells.
Interestingly, the entry of both wild-type and mutant variants into the host cell was significantly blocked by soluble ACE2, TMPRSS2 inhibitors and membrane fusion inhibitors. Compared to the wild-type virus, the variants showed a higher susceptibility to soluble ACE2-mediated inhibition. Similarly, the Brazil variant showed a higher sensitivity to membrane fusion inhibitors. These observations suggest that inhibitors of viral entry may be used to prevent infections mediated by mutant variants of SARS-CoV-2.
Despite comparable interaction dynamics between host cell and virus, significant differences in the antibody-mediated neutralization between the wild-type virus and the mutated variants were observed. Of the monoclonal antibodies tested, imdevimab showed comparable effectiveness in inhibiting host cell entry by all viral variants. In contrast, both South Africa and Brazil variants showed partial and complete resistance to casirivimab and bamlanivimab. However, all antibodies tested showed high effectiveness in inhibiting the UK variant.
Neutralizing antibodies generated in response to SARS-CoV-2 infection are expected to provide protection against re-infection. To determine the effectiveness of convalescence plasma therapy against viral variants, plasma samples obtained from COVID-19 patients with high wild-type spike protein-neutralizing effectiveness were tested against all viral variants. The results showed that the entry of host cells via the spike protein of the variants in South Africa and Brazil was inhibited less efficiently by the majority of the plasma samples tested. This indicates that people who were previously infected with wild-type SARS-CoV-2 are only partially protected against variants from South Africa and Brazil.
In terms of vaccine-mediated protection, the results indicated that most serum samples obtained from individuals vaccinated with BNT162b2 were less effective in inhibiting the entry of spike-driven host cells than those obtained from wild-type SARS-CoV-2 and observed the UK variant.
The study shows that current therapeutic interventions are less effective in inhibiting SARS-CoV-2 variants in South Africa and Brazil. Therefore, strict implementation of non-pharmaceutical control measures is required to contain their transmission.
* Important NOTE
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice / health-related behavior, or be treated as established information.