Divergence of Delta and Beta Variants and SARS-CoV-2 Evolved in Advanced HIV Disease into Two Serological Phenotypes

SARS-CoV-2 continues to evolve variants which escape antibody neutralization and have enhanced transmission. One variant may escape immunity elicited by another, and the Delta variant has been reported to escape Beta variant infection elicited immunity. Mapping the serological distance between current and emerging variants will likely guide design of vaccines which can target all variants. Here we mapped neutralization of SARSCoV-2 ancestral and Beta and Delta variant viruses by antibodies elicited by each variant in SARS-CoV-2 convalescent individuals. We also serologically characterized and mapped SARS-CoV-2 which evolved from an ancestral strain in prolonged infection in an immunosuppressed individual due to advanced HIV disease. Beta virus showed moderate (7-fold) and Delta virus slight escape from neutralizing immunity elicited by ancestral virus infection. In contrast, Delta virus had pronounced escape from Beta elicited immunity (12fold), and Beta virus even stronger escape from Delta immunity (34-fold). Evolved virus had 9-fold escape from ancestral immunity, 27-fold escape from Delta immunity, but was effectively neutralized by Beta immunity. We conclude that Beta and Delta variants are serologically distant, further than each is from ancestral virus. An example of SARS-CoV2 evolved during advanced HIV disease immune suppression is serologically close to Beta and far from Delta. These results suggest that SARS-CoV-2 is diverging into distinct serological phenotypes which may become serotypes, and that vaccines tailored to one variant may become vulnerable to infections with another. Funding: This study was supported by the Bill and Melinda Gates award INV-018944 (AS), National Institutes of Health award R01 AI138546 (AS), South African Medical Research Council awards (AS, TdO, PLM) and National Institutes of Health U01 AI151698 (WVV). PLM is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the NRF (Grant No 9834). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Declaration of Interests: None to declare. Ethics Approval Statement: Nasopharyngeal and oropharyngeal swab samples and plasma samples were obtained from hospitalized adults with PCR-confirmed SARS-CoV-2 infection who were enrolled in a prospective cohort study approved by the Biomedical Research Ethics Committee at the University of KwaZulu–Natal (reference BREC/00001275/2020).