Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera

Abstract

The race to produce vaccines against SARS-CoV-2 began when the first sequence was published, and this forms the basis for vaccines currently deployed globally. Independent lineages of SARS-CoV-2 have recently been reported: UK–B.1.1.7, South Africa–B.1.351 and Brazil–P.1. These variants have multiple changes in the immunodominant spike protein which facilitates viral cell entry via the Angiotensin converting enzyme-2 (ACE2) receptor. Mutations in the receptor recognition site on the spike are of great concern for their potential for immune escape. Here we describe a structure-function analysis of B.1.351 using a large cohort of convalescent and vaccinee serum samples. The receptor binding domain mutations provide tighter ACE2 binding and widespread escape from monoclonal antibody neutralization largely driven by E484K although K417N and N501Y act together against some important antibody classes. In a number of cases it would appear that convalescent and some vaccine serum offers limited protection against this variant.

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.…”

Nanotechnology advances in pathogen- and host-targeted antiviral delivery: multipronged therapeutic intervention for pandemic control

“…However, as viruses possess various mutational strategies, viral mutations may arise and reduce the affinity of antibody drugs. In the case of COVID-19, for instance, emerging variants have begun to exhibit the capability to escape from neutralizing antibodies [111,112]. As receptor-mediated binding with surface molecules on the plasma membrane of cells is an indispensable process for viruses to invade host cells [113], this interaction has been exploited to design biomimetic nanoparticle possessing cell-like surfaces for virus targeting.…”

B-Cell Memory Responses to Variant Viral Antigens

“…After just over a year of the pandemic it has become obvious there is a serious problem with the emergence of viral envelope spike protein variants that are impacting virus transmissibility and vaccine-and infection-induced antibody based immunity. Current SARS-CoV-2 mutations are collected in two areas, the N-terminal domain, where they reduce neutralizing antibody binding, and in the RBD where they have a complex effect on transmissibility and immune escape by increasing RBD affinity for its ACE2 receptor and reducing binding of neutralizing antibodies [65].…”

“…Of particular current concern are the B.1.351 'South African' variant and the P.1 'Brazil' variant, as there is now strong evidence their mutations enable escape from neutralization, as measured in vitro, by convalescent plasma and monoclonal antibodies [66], and serum from current vaccinees [65]. The B.1.351 variant shows a reduction in neutralization by current vaccine sera of around 7-to 9-fold.…”