Correlates of Neutralization against SARS-CoV-2 Variants of Concern by Early Pandemic Sera

Abstract

Emerging SARS-CoV-2 variants of concern that overcome natural and vaccine-induced immunity threaten to exacerbate the COVID-19 pandemic. Increasing evidence suggests that neutralizing antibody (NAb) responses are a primary mechanism of protection against infection. However, little is known about the extent and mechanisms by which natural immunity acquired during the early COVID-19 pandemic confers cross-neutralization of emerging variants. In this study, we investigated cross-neutralization of the B.1.1.7 and B.1.351 SARS-CoV-2 variants in a well-characterized cohort of early pandemic convalescent subjects. We observed modestly decreased cross-neutralization of B.1.1.7 but a substantial 4.8-fold reduction in cross-neutralization of B.1.351. Correlates of cross-neutralization included receptor binding domain (RBD) and N-terminal domain (NTD) binding antibodies, homologous NAb titers, and Membrane-directed T cell responses. These data shed light on cross-neutralization of emerging variants by early pandemic convalescent immune responses. IMPORTANCE Widespread immunity to SARS-CoV-2 will be necessary to end the COVID-19 pandemic. Neutralizing antibody (NAb) responses are a critical component of immunity that can be stimulated by natural infection as well as vaccines. However, SARS-CoV-2 variants are emerging that contain mutations in the Spike gene that promote evasion from NAb responses. These variants may therefore delay control of the COVID-19 pandemic. We studied whether NAb responses from early COVID-19 convalescent patients are effective against the two SARS-CoV-2 variants B.1.1.7 and B.1.351. We observed that the B.1.351 variant demonstrates significantly reduced susceptibility to early pandemic NAb responses. We additionally characterized virologic, immunologic, and clinical features that correlate with cross-neutralization. These studies increase our understanding of emerging SARS-CoV-2 variants.

Immunogenic and efficacious SARS-CoV-2 vaccine based on resistin-trimerized spike antigen SmT1 and SLA archaeosome adjuvant

“…In the case of B.1.351, we did detect a reduced capacity for neutralization by our immunized hamster serum, especially in animals receiving a single vaccine dose. Again, this was similar to previous reports showing reduced neutralization of B.1.351 by antibodies generated against antigen from the reference strain (via infection or vaccination) 23 , 24 . Interestingly, B.1.351 neutralization was still strongly mediated by the serum of animals receiving a double dose adjuvanted vaccine regimen, especially the formulation adjuvanted with SLA + CpG.…”

“…Also, with the emergence of viral variants, highly immunogenic vaccines capable of inducing strong humoral and cellular immune responses would be more likely to cross-protect against so-called SARS-CoV-2 variants of concerns, such as B.1.1.7 and B.1.351, originally identified in UK and South Africa, respectively. While antigen-specific T cell responses cross-react well to the SARS-CoV-2 variants, mutations in B.1.351 spike protein have been shown to make it more resistant to antibodies developed against the spike protein of the reference strain, originally identified in Wuhan 22 – 24 .…”

Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice

“…These NAb levels were significantly greater than those elicited by the WT sequence both postprime and postboost. For comparison, we previously reported NAb titers from human convalescent sera between 10 2 and 10 3 using the same pseudovirus neutralization assay ( 34 , 35 ).…”

Intra-host SARS-CoV-2 evolution in the gut of mucosally-infected Chlorocebus aethiops (African green monkeys)

“…As a result, several new variants have emerged with enhanced replicative or infectious capacity and immune escape [1]. Since the discovery of the D614G mutation [2,3], noted early in the pandemic and found to enable enhanced infection in cells and is now present in all sequenced isolates, several variants of interest and concern (as defined by the CDC) have arisen [1,[4][5][6][7][8][9][10][11].…”