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Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum

Our take —

This study provides a detailed analysis of antibody neutralization in vitro of the B.1.617.1 and B.1617.2 (Delta) SARS-CoV-2 variants of concern, which were first identified from cases in India in early 2021 and continue to spread rapidly across the globe. While the ability of both convalescent plasma and vaccine sera to neutralize these viruses was somewhat diminished, there was no evidence of widespread immune escape. Both doses of the Pfizer vaccine appeared to be required to maintain neutralizing responses against these variants, illustrating the importance of completing recommended vaccine regimens. Data also suggested that previous infection with B.1.351 (Beta variant) or P.1 (Gamma variant) may not be protective against reinfection with the Delta variant, indicating that these individuals may particularly benefit from vaccination. Additional studies are needed to determine the prevalence and severity of reinfection and vaccine breakthrough infection associated with B.1.617.1/B.1.617.2. However, initial data suggest that the current vaccines and antibody-based treatments remain effective for the treatment and prevention of SARS-CoV-2 infection caused by these variants of concern.

Study design

Retrospective Cohort

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.

Study Strengths

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.

Limitations

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.

Value added

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