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First Author:  Vogl, Tet al. 

Journal/preprint name: medRxiv 

Tags: Antibodies, Cross-reactivity  


Using sera from recovered COVID-19 patients and unexposed individuals, the authors were able to demonstrate cross-reactive IgG responses to linear epitopes from a phase-displayed antigen library against SARS-CoV-2, other epidemic strains and seasonal coronaviruses. Abundant antibody responses to seasonal coronaviruses were found in both groups, although particular peptides could only be bound by recovered sera. Peptides that elicit cross-reactive responses are typically within the spike and nucleocapsid, which may have implications for vaccine design. Vast inter-individual variability of responses towards SARS-CoV-2 peptides in recovered COVID-19 patients was also found. 

Research Highlights 

  1. Broad antibody responses against peptides of seasonal hCoVs were seen in up to 75% of samples. Binding to particular peptides were comparable between recovered and unexposed individuals. 

  1. Sera from recovered COVID-19 patients bound to SARS-CoV-1 and SARS-CoV-2 peptides more significantly than in unexposed individuals. However, no convergence of responses towards a particular SARS-CoV-2 peptide was found, demonstrating substantial inter-individual variability between samples. 

  1. Particular epitopes from seasonal strains (e.g. hCOV-OC43) were more significantly bound by recovered COVID-19 sera however limited cross-reactivity towards alpha-coronaviruses was seen. 

  1. Peptides that induced cross-reactive responses were typically found within similar regions of the nucleocapsid and spike, particularly the S2 region. Vaccines that only use RBD of spike may induce responses which are unable to cross-react as well. 

Impact for COVID-19 research:  

  • Cross-reactivity has multiple implications for vaccine design, diagnostic tools and long-term protection. The authors cite multiple studies that have showed similar trends to themselves.  


  • Study Type: in vitro, in silico 

  • Key Techniques: Phase immunoprecipitation sequencing (PhIP-Seq) library with 64 amino acid peptides (20 amino acid overlap) 


  1. Linear peptides do not reflect the complex 3D organisation of viral proteins. May demonstrate why few response towards peptides in RBD were seen. 

  1. By authors own admission, PhIP-Seq has its own limitations with regards to lacking of post-translational modifications to peptides, particularly glycosylation. 

  1. Only mild recovered patients were included. It would be good to see how responses differ due to severity. 

  1. Authors also acknowledge the neutralising capacity of these interactions were not determined