Emerging SARS-CoV-2 variants of concern evade humoral immune responses from infection and vaccination

Abstract

Emerging SARS-CoV-2 variants of concern (VOCs) pose a threat to human immunity induced by natural infection and vaccination. We assessed the recognition of three VOCs (B.1.1.7, B.1.351, and P.1) in cohorts of COVID-19 convalescent patients (n = 69) and Pfizer-BioNTech vaccine recipients (n = 50). Spike binding and neutralization against all three VOCs were substantially reduced in most individuals, with the largest four-to sevenfold reduction in neutralization being observed against B.1.351. While hospitalized patients with COVID-19 and vaccinees maintained sufficient neutralizing titers against all three VOCs, 39% of nonhospitalized patients exhibited no detectable neutralization against B.1.351. Moreover, monoclonal neutralizing antibodies show sharp reductions in their binding kinetics and neutralizing potential to B.1.351 and P.1 but not to B.1.1.7. These data have implications for the degree to which pre-existing immunity can protect against subsequent infection with VOCs and informs policy makers of susceptibility to globally circulating SARS-CoV-2 VOCs.

Probing Affinity, Avidity, Anticooperativity, and Competition in Antibody and Receptor Binding to the SARS-CoV-2 Spike by Single Particle Mass Analyses

“…This binding loss is expected as COVA1-18 is unable to neutralize B.1.351, while COVA2-15 has substantially reduced activity. 10 , 55 These results strengthen the arguments for the necessity of using multiple Abs (cocktails) for the design of target biotherapeutic treatments and also highlight the potential of mass photometry and charge-detection mass spectrometry to guide Ab design and development.…”

A third SARS-CoV-2 spike vaccination improves neutralization of variants-of-concern

“…The Delta variant, which originated in India, carries the T19R, G142D, 156–157 deletion and R158G in the NTD, and L452R and T478K in the RBD 17 . While the Alpha variant is more infectious, it is only slightly more resistant to neutralization by sera from convalescent patients and vaccinees compared to B.1 14 , 15 , 18 – 21 . In contrast, mutations in the Beta S decrease the neutralization sensitivity of convalescent and vaccine sera by approximately sixfold (range: 4–42) 10 – 14 , 21 , while mutations in Gamma decrease neutralizing activity by approximately threefold (range: 2–7) 10 , 12 , 21 .…”

“…While the Alpha variant is more infectious, it is only slightly more resistant to neutralization by sera from convalescent patients and vaccinees compared to B.1 14 , 15 , 18 – 21 . In contrast, mutations in the Beta S decrease the neutralization sensitivity of convalescent and vaccine sera by approximately sixfold (range: 4–42) 10 – 14 , 21 , while mutations in Gamma decrease neutralizing activity by approximately threefold (range: 2–7) 10 , 12 , 21 . Delta shows increased transmissibility 22 and was approximately threefold less sensitive to neutralization (range: 2–5) 23 , 24 .…”

“…This construct contains proline substitutions at 986 and 987, and a GGGG substitution at the furin cleavage site (682–685). The SARS-CoV-2-S-B.1 Δ19 , SARS-CoV-2-S-B.1.1.7 Δ19 , SARS-CoV-2-S-B.1.351 Δ19 , SARS-CoV-2-S-P.1 Δ19 plasmids were described elsewhere and SARS-CoV-2-S-B.1.617.2 Δ19 was made as described elsewhere 21 . In brief, gBlock gene fragments (Integrated DNA technologies) we ordered and cloned SacI/ApaI into the pCR3 SARS-CoV-2-S Δ19 expression plasmid (GenBank: MT449663.1).…”

“…A custom Luminex assay was used as described previously 29 . In short, prefusion stabilized trimeric spike proteins of all SARS-CoV-2 variants 21 , were produced in HEK293F cells and purified by Ni-NTA chromatography followed by size-exclusion chromatography step. Prefusion stabilized trimeric SARS-CoV-2 B.1.617.2 Spike was provided by Dirk Eggink and Chantal Reusken (National Institute for Public Health and the Environment, the Netherlands).…”