Neutralization of viruses with European, South African, and United States SARS-CoV-2 variant spike proteins by convalescent sera and BNT162b2 mRNA vaccine-elicited antibodies

Abstract

The increasing prevalence of SARS-CoV-2 variants with mutations in the spike protein has raised concerns that recovered individuals may not be protected from reinfection and that current vaccines will become less effective. The B.1.1.7 isolate identified in the United Kingdom and B.1.351 isolate identified in the Republic of South Africa encode spike proteins with multiple mutations in the S1 and S2 subunits. In addition, variants have been identified in Columbus, Ohio (COH.20G/677H), Europe (20A.EU2) and in domesticated minks. Analysis by antibody neutralization of pseudotyped viruses showed that convalescent sera from patients infected prior to the emergence of the variant viruses neutralized viruses with the B.1.1.7, B.1.351, COH.20G/677H Columbus Ohio, 20A.EU2 Europe and mink cluster 5 spike proteins with only a minor decrease in titer compared to that of the earlier D614G spike protein. Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera. Vaccine elicited antibodies neutralized virus with the B.1.1.7 spike protein with titers similar to D614G virus and neutralized virus with the B.1.351 spike with, on average, a 3-fold reduction in titer (1:500), a titer that was still higher than the average titer with which convalescent sera neutralized D614G (1:139). The reduction in titer was attributable to the E484K mutation in the RBD. The B.1.1.7 and B.1.351 viruses were not more infectious than D614G on ACE2.293T cells in vitro but N501Y, an ACE2 contacting residue present in the B.1.1.7, B.1.351 and COH.20G/677H spike proteins caused higher affinity binding to ACE2, likely contributing to their increased transmissibility. These findings suggest that antibodies elicited by primary infection and by the BNT162b2 mRNA vaccine are likely to maintain protective efficacy against B.1.1.7 and most other variants but that the partial resistance of virus with the B.1.351 spike protein could render some individuals less well protected, supporting a rationale for the development of modified vaccines containing E484K.

Reduced neutralization of B.1.351 variant SARS-CoV-2 by convalescent sera of COVID-19 patients

“…The obtained results are in line with previous studies reporting lowered NAb levels against B1.351 variant when compared to B1.1.7 or the older dominant strains 19,8,17,18,25 . Although previous studies have shown that pseudotype neutralization results have good concordance with SARS-CoV-2 neutralization assays 26 , it is necessary to have con rmatory data also using actual low-passage replicating clinical isolates that contain sets of mutations present in circulating strains.…”

“…The recently emerged variants of SARS-CoV-2 with phenotype affecting mutations in the RBD are of concern either due to increased transmissibility or because neutralization escape variants may lower the protective immunity of vaccinees and recoverees. Initial reports using small numbers of tested sera and a variety of techniques such as SARS-CoV-2 spike-variant pseudotyped lentivirus 17,18 or VSV 19 , infectious clones and virus isolates 20 have demonstrated differences in the levels of neutralizing activity of MAbs, convalescent patient and vaccinee sera. The trend in the results is, that the B.1.1.7-variant is neutralized nearly equally to the original virus type, whereas the B.1.351 variant is less well neutralized.…”

An observational cohort study on the incidence of SARS-CoV-2 infection and B.1.1.7 variant infection in healthcare workers by antibody and vaccination status

“…21 Reinfection rates following natural infection have not been shown to be higher in studies using SGTF as a proxy for B.1.1.7, 20,22 even though variably decreased sensitivity to neutralisation by monoclonal antibodies, convalescent plasma and sera from vaccinated individuals has been observed in vitro for B.1.1.7. [23][24][25][26][27][28][29][30][31][32][33][34] The Oxford-AstraZeneca trial showed good vaccine efficacy against sequencingconfirmed symptomatic B.1.1.7, despite evidence of decreased neutralising titres, but decreased efficacy for asymptomatic/unknown symptom infections. 35 Pfizer-BioNTech vaccine effectiveness in HCWs appears preserved despite increasing B.1.1.7 incidence in the UK; however these studies have not specifically investigated cases of SGTF or sequencing-confirmed B.1.1.7.…”

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

“…E484K was responsible for near complete resistance against multiple NTD and RBD mAbs and up to >10 and >30 times lower nAb titers in vaccinees and convalescent individuals, respectively. N501Y or K417N are additional mutations, all in RBD, conferring reduced nAb activity in SARS-CoV-2 vaccine and convalescent sera [292,293,296,297,[321][322][323][324][325][326][327][328]. These results could be recapitulated in experiments with SARS-CoV-2 isolates [329][330][331], whereas another study with recombinant SARS-CoV-2 carrying the specific point mutations reported smaller effects on nAb titers against infectious SARS-CoV-2 [332].…”

“…Some of these second-wave Spike mutations seem to confer partial neutralization resistance, as measured in in vitro assays with convalescent or vaccine sera [292][293][294][295][296][297]. Available potent vaccines at optimal dosing can induce multiple times higher nAb titers than convalescent sera [293,[298][299][300] and might thus have a broader window to compensate for partial Ab escape. The enrichment of second wave Spike variants (Table 2, Figure 6) suggests that Ab-mediated immunity, either obtained by SARS-CoV-2 infection or by vaccination, may have exerted critical selective pressure [80].…”