Dataset Information

Mapping SARS-CoV-2 antigenic relationships and serological responses.

ABSTRACT: During the SARS-CoV-2 pandemic, multiple variants with differing amounts of escape from pre-existing immunity have emerged, causing concerns about continued protection. Here, we use antigenic cartography to quantify and visualize the antigenic relationships among 16 SARS-CoV-2 variants titrated against serum samples taken post-vaccination and post-infection with seven different variants. We find major antigenic differences caused by substitutions at spike positions 417, 452, 484, and possibly 501. B.1.1.529 (Omicron BA.1) showed the highest escape from all sera tested. Visualization of serological responses as antibody landscapes shows how reactivity clusters in different regions of antigenic space. We find changes in immunodominance of different spike regions depending on the variant an individual was exposed to, with implications for variant risk assessment and vaccine strain selection.

One sentence summary

Antigenic Cartography of SARS-CoV-2 variants reveals amino acid substitutions governing immune escape and immunodominance patterns.

SUBMITTER: Wilks SH

PROVIDER: S-EPMC9298128 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Mapping SARS-CoV-2 antigenic relationships and serological responses.

Wilks Samuel H SH Mühlemann Barbara B Shen Xiaoying X Türeli Sina S LeGresley Eric B EB Netzl Antonia A Caniza Miguela A MA Chacaltana-Huarcaya Jesus N JN Corman Victor M VM Daniell Xiaoju X Datto Michael B MB Dawood Fatimah S FS Denny Thomas N TN Drosten Christian C Fouchier Ron A M RAM Garcia Patricia J PJ Halfmann Peter J PJ Jassem Agatha A Jeworowski Lara M LM Jones Terry C TC Kawaoka Yoshihiro Y Krammer Florian F McDanal Charlene C Pajon Rolando R Simon Viviana V Stockwell Melissa S MS Tang Haili H van Bakel Harm H Veguilla Vic V Webby Richard R Montefiori David C DC Smith Derek J DJ

bioRxiv : the preprint server for biology 20230616

During the SARS-CoV-2 pandemic, multiple variants escaping pre-existing immunity emerged, causing concerns about continued protection. Here, we use antigenic cartography to analyze patterns of cross-reactivity among a panel of 21 variants and 15 groups of human sera obtained following primary infection with 10 different variants or after mRNA-1273 or mRNA-1273.351 vaccination. We find antigenic differences among pre-Omicron variants caused by substitutions at spike protein positions 417, 452, 48 ...[more]

PMID: 35860221

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Project description:As public health guidelines throughout the world have relaxed in response to vaccination campaigns against SARS-CoV-2, it is likely that SARS-CoV-2 will remain endemic, fueled by the rise of more infectious SARS-CoV-2 variants. Moreover, in the setting of waning natural and vaccine immunity, reinfections have emerged across the globe, even among previously infected and vaccinated individuals. As such, the ability to detect reexposure to and reinfection by SARS-CoV-2 is a key component for global protection against this virus and, more importantly, against the potential emergence of vaccine escape mutations. Accordingly, there is a strong and continued need for the development and deployment of simple methods to detect emerging hot spots of reinfection to inform targeted pandemic response and containment, including targeted and specific deployment of vaccine booster campaigns. In this study, we identify simple, rapid immune biomarkers of reinfection in rhesus macaques, including IgG3 antibody levels against nucleocapsid and FcγR2A receptor binding activity of anti-RBD antibodies, that are recapitulated in human reinfection cases. As such, this cross-species analysis underscores the potential utility of simple antibody titers and function as price-effective and scalable markers of reinfection to provide increased resolution and resilience against new outbreaks. IMPORTANCE As public health and social distancing guidelines loosen in the setting of waning global natural and vaccine immunity, a deeper understanding of the immunological response to reexposure and reinfection to this highly contagious pathogen is necessary to maintain public health. Viral sequencing analysis provides a robust but unrealistic means to monitor reinfection globally. The identification of scalable pathogen-specific biomarkers of reexposure and reinfection, however, could significantly accelerate our capacity to monitor the spread of the virus through naive and experienced hosts, providing key insights into mechanisms of disease attenuation. Using a nonhuman primate model of controlled SARS-CoV-2 reexposure, we deeply probed the humoral immune response following rechallenge with various doses of viral inocula. We identified virus-specific humoral biomarkers of reinfection, with significant increases in antibody titer and function upon rechallenge across a range of humoral features, including IgG1 to the receptor binding domain of the spike protein of SARS-CoV-2 (RBD), IgG3 to the nucleocapsid protein (N), and FcγR2A receptor binding to anti-RBD antibodies. These features not only differentiated primary infection from reexposure and reinfection in monkeys but also were recapitulated in a sequencing-confirmed reinfection patient and in a cohort of putatively reinfected humans that evolved a PCR-positive test in spite of preexisting seropositivity. As such, this cross-species analysis using a controlled primate model and human cohorts reveals increases in antibody titers as promising cross-validated serological markers of reinfection and reexposure.

Dataset Information

Mapping SARS-CoV-2 antigenic relationships and serological responses.

One sentence summary

Publications

Mapping SARS-CoV-2 antigenic relationships and serological responses.

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