This is a summary, written by members of the CITF Secretariat, of:

N’Guessan A, Kailasam S, Mostefai F, Poujol R, Grenier JC, Ismailova N, Contini P, De Palma R, Haber C, Stadler V, Bourque G, Hussin JG, Shapiro BJ, Fritz JH, Piccirillo CA. Selection for immune evasion in SARS-CoV-2 revealed by high-resolution epitope mapping and sequence analysis. iScience. 2023 Jul 13;26(8):107394. doi: 10.1016/j.isci.2023.107394.

The results and/or conclusions contained in the research do not necessarily reflect the views of all CITF members.

A CITF-funded study, published in iScience, found that transmission between hosts leads to mutations that cause immune evasion (when the immune system does not recognize a virus and does not mount a fight). The study also offered more evidence that exposure to other seasonal human coronaviruses (hCoVs) helps develop a better immune response to SARS-CoV-2.

The study, led by Drs. Ciriaco A Piccirillo and Jörg Fritz (both McGill University), identified hotspots of pre-existing immunity and cross-reactive epitopes with other human coronaviruses that contribute to increasing the overall humoral immune response to SARS-CoV-2. Researchers assessed the evolutionary profile of epitopes and differences across proteins, pandemic waves, and SARS-CoV-2 variants. They found that mutations in spike and nucleocapsid epitopes are under stronger selection between patients, rather than within patients, suggesting that most of the selective pressure for immune evasion occurs upon transmission between hosts. This signals that the humoral immune response is a significant driver of virus evolution.

The study used sera obtained from 10 SARS-CoV-2-positive individuals (asymptomatic and recovered) and five SARS-CoV-2-negative control subjects (SARS-CoV-2-negative). It exploited a high-density peptide array (HDPA) spanning the entire proteomes of SARS-CoV-2 and endemic human coronaviruses – a deep serological profiling strategy and an integrated computational framework – to analyze SARS-CoV-2 humoral immune responses and identify the antigenic targets.

Key findings:

  • Assessing the entire proteomes of SARS-CoV-2 and endemic human coronaviruses allowed identification of B cell epitopes and their evolutionary and structural properties. This could facilitate better understanding of diagnostic markers, identification of correlates of protection, and monitoring of vaccine efficacy.
  • The study highlighted that antibody responses to seasonal human coronaviruses (involving OC43, HKU1, NL63 and 229E) cross-react with SARS-CoV-2 and these elicited immunological memory responses may reduce the severity of SARS-CoV-2 infections. This could be a reason why a large proportion of individuals with SARS-CoV-2 infection experience mild and asymptomatic disease symptoms.
  • The study also observed that variants of concern (VOCs) and variants under investigation (VUIs) contain significantly more signature epitope mutations than non-VOCs and non-VUIs. Thus, evasion of the humoral immune response is a significant driver of VOC/VUI evolution. Epitope mutations were found mostly in the VOCs Delta, C.36.3, and especially Omicron (B.1.1.529) and its sublineages.