Neutralizing activity of Sputnik V vaccine sera against SARS-CoV-2 variants

Abstract

The novel pandemic betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected at least 120 million people since its identification as the cause of a December 2019 viral pneumonia outbreak in Wuhan, China1,2. Despite the unprecedented pace of vaccine development, with six vaccines already in use worldwide, the emergence of SARS-CoV-2 ‘variants of concern’ (VOC) across diverse geographic locales have prompted re-evaluation of strategies to achieve universal vaccination3. All three officially designated VOC carry Spike (S) polymorphisms thought to enable escape from neutralizing antibodies elicited during initial waves of the pandemic4–8. Here, we characterize the biological consequences of the ensemble of S mutations present in VOC lineages B.1.1.7 (501Y.V1) and B.1.351 (501Y.V2). Using a replication-competent EGFP-reporter vesicular stomatitis virus (VSV) system, rcVSV-CoV2-S, which encodes S from SARS coronavirus 2 in place of VSV-G, and coupled with a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection, we determined that only 1 out of 12 serum samples from a cohort of recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) of rcVSV-CoV2-S: B.1.351 at full serum strength. The same set of sera efficiently neutralized S from B.1.1.7 and showed only moderately reduced activity against S carrying the E484K substitution alone. Taken together, our data suggest that control of some emergent SARS-CoV-2 variants may benefit from updated vaccines.

Anti-SARS-CoV-2 Antibodies Testing in Recipients of COVID-19 Vaccination: Why, When, and How?

“…In a seminal article published by Hoffmann et al, it was recently reported that the neutralizing potency of antibodies elicited after SARS-CoV-2 infection or COVID-19 vaccination would be decreased by approximately 1.7-, 5.0-, and 7.9-fold versus the B.1.1.7, P.1, and B.1.351 lineages, respectively [38]. Similar data were published by others regarding the recipients of different vaccine formulations, such as Pfizer BNT162b2 or Oxford-AstraZeneca ChAdOx1 nCoV-19 [39], Pfizer BNT162b2 or Moderna mRNA-1273 [40], or Sputnik Gam-COVID-Vac [41]. This biological evidence may then translate into a tangible clinical risk, as was recently reported by some preliminary prospective studies.…”

Systematic genome-scale identification of host factors for SARS-CoV-2 infection across models yields a core single gene dependency; ACE2

“…Indeed, this is consistent with a previous report, in which inhibition of cathepsin L (CTSL) and cathepsin B (CTSB) in 293T+ACE2 cells reduced entry of pseudotyped-Spike viruses, whereas inhibiting TMPRSS2 did not, indicating that SARS-CoV-2 entry into 293T-ACE2 cells depends on CTSB or CTSL. Therefore, it appears that exogenous TMPRSS2 may be redundant due to the underlying effect of endogenous CTSB/L expression, which was not identified in our HEK293 +A+T screen (Crawford et al, 2020; Hu et al, 2020; Ikegame et al, 2021).…”

COVID-19: Unmasking Emerging SARS-CoV-2 Variants, Vaccines and Therapeutic Strategies

“…In addition, sera from the Moderna and Pfizer-BioNTech vaccines show significantly reduced neutralization of B.1.351 (12.4 fold, Moderna; 10.3 fold, Pfizer) [192]. The Gam-Covid-Vac Sputnik V vaccine sera exhibited moderate and markedly reduced neutralization titers, against E484K and B.1.351 variants respectively [193]. Serum samples obtained after the second dose of the BBIBP-CorV vaccine (Sinopharm) or CoronaVac vaccine serum samples showed complete or partial loss of neutralization against B.1.351 [197].…”

“…The Gam-Covid-Vac Sputnik V vaccine sera effectively neutralized B.1.1.7. viruses, albeit with highly variable titers, while NVX-CoV2373 demonstrated an efficacy rate of 86.3% against mild, moderate and severe COVID-19 caused by B.1.1.7 as compared to 96% efficacy seen in the wild-type B1 strain [74,193]. Overall, although there are variations in study design, the efficacy of currently available vaccines is either similar or moderately lower against the B.1.1.7 variant (Table 6).…”

“…Ad26.COV2.S: 52% efficacy against moderate disease,72% efficacy against severe disease [224] 5. Gam-Covid-Vac: abolished [193] 6. Complete or partial loss of neutralization against BBIBP-CorV (Sinopharm)…”