Novel SARS-CoV-2 Variants Partially Resistant To Infection-
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A recent study conducted has revealed that while severely affected hospitalized COVID-19 patients and vaccinated individuals are capable of neutralizing the B.1.1.7, B.1.351, and P.1 variants of SARS-CoV-2, a significant proportion of non-hospitalized patients with less severe COVID-19 remain susceptible to these viral variants.

For antibody testing, serum samples were obtained from 69 COVID-19 patients 4 – 6 weeks after the symptom onset. An additional set of serum samples was collected from 50 vaccinated healthcare workers 4 weeks after the 2nd vaccine dose. The participants received the mRNA-based COVID-19 vaccine developed by Pfizer/BioNTech.

The spike proteins of wild-type SARS-CoV-2 and three VOCs were generated and used to measure the binding antibody responses of collected serum samples using multiplex protein microarray. To determine the neutralizing ability of sera, lentiviral-based pseudoviruses of the wild-type virus and three VOCs were utilized.

~ Important observations

The study findings revealed that compared to the wild type SARS-CoV-2, the spike binding ability of convalescent sera reduced by 2.4-fold, 3-fold, and 4-fold for the B.1.1.7, B.1.351, and P.1 variants, respectively. Moreover, a highly significant difference in spike-binding antibody levels was observed between severely affected hospitalized COVID-19 patients and mildly affected non-hospitalized COVID-19 patients.

A comparable level of binding antibody was observed in vaccinated individuals and hospitalized patients, which was 4 – 11 times higher than non-hospitalized patients. All these observations were consistent for all tested VOCs. Regarding virus neutralization, about 96% of convalescent sera and 100% of vaccinated sera exhibited complete neutralizing ability against the wild-type virus. However, all tested sera showed a significant reduction in neutralization potency against the VOCs.

While 100% of non-hospitalized patients showed neutralizing titers against the wild-type virus and B.1.1.7 variant, about 39% and 34% of them failed to neutralize the B.1.351 and P.1 variants, respectively. In contrast, all hospitalized patients and vaccinated individuals retained at least some neutralization ability against the VOCs. Overall, these observations indicate that a high neutralizing titer against the wild-type virus is predictive for cross-neutralization of VOCs.

Regarding monoclonal antibodies, preclinically tested anti-RBD and anti-NTD (N-terminal domain) antibodies showed significantly reduced binding against the B.1.351 and P.1 variants compared to that against the wild-type virus. However, some SARS-CoV cross-reactive anti-RBD monoclonal antibodies retained similar binding kinetics to all tested VOCs. The mutational analysis of VOCs revealed that the E484K mutation, together with other mutations such as K417N and K417T, had the highest impact on the binding of monoclonal anti-RBD antibodies.

Regarding virus neutralization, only 5 out of 11 tested anti-RBD monoclonal antibodies retained neutralizing ability against the B.1.351 and P.1 variants. However, both anti-NTD antibodies failed to neutralize the B.1.351 variant. Importantly, SARS-CoV cross-reactive monoclonal antibody successfully retained its ability to neutralize all tested VOCs. This indicates that this antibody targets a highly conserved epitope that is not impacted by the mutations found in these VOCs.

~ Study significance

The study findings reveal that despite having a low binding and neutralizing titers, hospitalized patients with severe COVID-19 and vaccinated individuals are capable of neutralizing the B.1.1.7, B.1.351, and P.1 variants of SARS-CoV-2. However, mildly affected non-hospitalized COVID-19 patients fail to induce sufficient neutralizing titers against these VOCs. Among tested VOCs, B.1.351 variant exhibits the highest resistance to antibody-mediated neutralization.

Source:
https://doi.org/10.1101/2021.05.26.21257441
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