Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies

Abstract

SARS-CoV-2 B.1.1.7 and B.1.351 variants emerged respectively in United Kingdom and South Africa and spread in many countries. Here, we isolated infectious B.1.1.7 and B.1.351 strains and examined their sensitivity to anti-SARS-CoV-2 antibodies present in sera and nasal swabs, in comparison with a D614G reference virus. We established a novel rapid neutralization assay, based on reporter cells that become GFP+ after overnight infection. B.1.1.7 was neutralized by 79/83 sera from convalescent patients collected up to 9 months post symptoms, almost similar to D614G. There was a mean 6-fold reduction in titers and even loss of activity against B.1.351 in 40% of convalescent sera after 9 months. Early sera from 19 vaccinated individuals were almost as potent against B.1.1.7 but less efficacious against B.1.351, when compared to D614G. Nasal swabs from vaccine recipients were not neutralizing, except in individuals who were diagnosed COVID-19+ before vaccination. Thus, faster-spreading variants acquired a partial resistance to humoral immunity generated by natural infection or vaccination, mostly visible in individuals with low antibody levels.

ChAdOx1 nCoV-19 (AZD1222) protects Syrian hamsters against SARS-CoV-2 B.1.351 and B.1.1.7

“…Whereas we did find these substitutions in swabs obtained 1 DPI, they were not present in swabs obtained at 5 DPI. Likewise, the substitutions were only found in lung tissue of one out of four control hamsters ( conclude that the substitutions found in the B.1.1.7 spike protein have limited to no effect on virus neutralization titres [9][10][11][12][13][14][15] . Data from a UK phase III trial taken from a time when B.1.1.7 predominated, showed minimal impact on ChAdOx1 nCoV-19 vaccine efficacy .…”

“…Likewise, in an observational study of vaccine effectiveness in adults aged over 70 years in the UK, a single dose of either ChAdOx1 nCoV-19 or the Pfizer/BioNTech vaccine BNT162b2 reduced hospitalization in elderly adults with co-morbidities by 80% 16 . In contrast, the substitutions found in the B.1.351 spike protein (Table 1) result in a significant reduction of virus neutralizing capacity with pseudotype or infectious virus neutralization assays [9][10][11][12][13][14][15]17,18 . In a phase II study of It should be noted that the B.1.351 virus stock used to challenge hamsters contained two additional non-fixed AA substitutions; Q677H and R682W at 88% and 89%, respectively.…”

Serological reconstruction of COVID-19 epidemics through analysis of antibody kinetics to SARS-CoV-2 proteins

“…213 serum samples from 194 patients in Dublin hospitals were collected, with date post symptom onset extending to four months. 724 serum samples from 347 healthcare workers in Strasbourg hospitals were collected, with date post symptom onset extending to nine months 32 .…”

“…The data from our multiplex assay was compared against data from two different neutralization assays with live virus using a subset of serum samples. Firstly, we implemented an S-Fuse assay as described elsewhere 32…”

Mutational escape from the polyclonal antibody response to SARS-CoV-2 infection is largely shaped by a single class of antibodies

“…But a little over a year into the pandemic, a proliferating number of new viral lineages are rising in frequency [1][2][3][4][5][6] . These emerging lineages have mutations at <1% of all residues in the viral spike, and at no more than 3 of the ~200 residues in the spike receptor-binding domain (RBD)-yet these handfuls of mutations often substantially erode and in some cases even ablate the polyclonal neutralizing antibody response elicited by infection [7][8][9][10][11][12][13][14][15][16] .…”