Study population and setting
Neutralizing antibodies targeting spike protein are elicited by natural infection with SARS-CoV-2 and vaccination against SARS-CoV-2. Viral variants harbor mutations that may allow for evasion of these neutralizing antibodies, resulting in reinfections and vaccine breakthrough infections. The highly transmissible B.1.617.1 and B.1.617.2 (Delta) variants originated in India in the spring of 2021. This study described the ability of these two variants to be neutralized by monoclonal antibodies (for both research and clinical use), convalescent plasma (collected post-infection with wild-type [n=34], B.1.1.7 Alpha [n=18], P.1 Gamma [n=17], and B.1.351 Beta [n=14] virus) and post-vaccination sera (Oxford-AstraZeneca [n=25] and Pfizer-BioNTech [n=25]). Neutralization was measured using either a pseudovirus or live virus assay; results were reported in comparison to the Victoria strain (highly similar to the original Wuhan strain). Neutralization assays were also performed with sera collected after only one dose of the Pfizer-BioNTech vaccine (n=20). Structural analysis of antibody binding to wild-type and variant SARS-CoV-2 was completed using x-ray crystallography. A new method, termed “antigenic cartography” was developed to estimate the antigenic distance between different viral lineages; this method used single value decomposition to return a graphical display of inter-strain antigenic relationships.
Summary of Main Findings
Monoclonal antibodies from a panel designed for research use displayed a more than 5-fold decreased neutralization of B.1.617.1 (8/20 antibodies) and B.1.617.2 Delta (7/20 antibodies), likely due to the L452R mutation found in both variants. However, monoclonal antibodies currently approved for treatment (i.e., Regeneron) remained effective, with only slight reductions in neutralization activity; the one exception was LY-CoV555, which was not effective against either variant. Neutralization of both B.1.617.1 and B.1.617.2 with convalescent plasma collected from persons previously infected with either wild-type virus or the Alpha variant was only mildly reduced. In contrast, neutralization of B.1.617.2 with convalescent plasma from persons previously infected with the Beta or Gamma variants was profoundly diminished, suggesting that those persons may be at increased risk of reinfection. Mean neutralization titers against the B.1.617.1 and B.1617.2 (Delta) variants were mildly reduced (but still adequately protective) for both the Pfizer-BioNTech and Oxford-Astra-Zeneca post-vaccine sera. However, at 10 weeks post-vaccination, all 20 individuals who received only one dose of the Pfizer-BioNTech vaccine had inadequate neutralization titers against both variants, indicating an increased risk of vaccine breakthrough infection among persons with incomplete vaccine schedules. Using antigenic cartography, the largest antigenic distance was found between B.1.351/P.1 and B.1.617.2.
This study provides a comprehensive analysis of the neutralization performance of monoclonal antibodies, convalescent plasma, and post-vaccination sera against the B.1.617.1 and B.1.617.2 (Delta) SARS-CoV-2 variants of concern.
Neutralization of B.1.617.1 and Victoria was measured using a pseudovirus-based assay vs. live virus, and these results were compared with data collected using a live virus assay for B.1.617.2 (Delta). All neutralization assays were completed in the absence of other important components of the immune system (i.e., complement, T-cells) whose effector functions may remain intact in cases of infection with B.1.617.1 or B.1.617.2. Epitope-level analysis of cross-reactive protective responses was also not included in this study. The neutralization mechanism for some antibodies included in this study is also still poorly understood. Additional epidemiologic data is required to determine the prevalence of B.1.617.1/B.1.617.2 reinfection/vaccine breakthrough infection and the associated risk of severe disease, hospitalization, or death.
This study provides the first in-depth analysis of neutralizing antibody responses (from previous natural infection, vaccination, or as part of antibody-based treatment regimens) against the B.1.617.1 and B.1.617.2 (Delta) SARS-CoV-2 variants of concern.
This review was posted on: 26 June 2021