Non-Neutralizing Epitopes Shade Neutralizing Epitopes against Omicron in a Multiple Epitope-Based Vaccine

Abstract

The ongoing coronavirus disease 2019 pandemic has raised concerns about the risk of re-infection. Non-neutralizing epitopes are one of the major reasons for antibody-dependent enhancement. Past studies on the ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have revealed an infectivity-enhancing site on the ancestral SARS-CoV-2 spike protein. However, infection enhancement associated with the SARS-CoV-2 Omicron strain remains elusive. In this study, we examined the antibodies induced by a multiple epitope-based vaccine, which showed infection enhancement for the Omicron strain but not for the ancestral SARS-CoV-2 or Delta strain. By examining the antibodies induced by single epitope-based vaccines, we identified a conserved epitope, IDf (450−469), with neutralizing activity against ancestral SARS-CoV-2, Delta, and Omicron. Although neutralizing epitopes are present in the multiple epitope-based vaccine, other immunodominant non-neutralizing epitopes such as IDg (480−499) can shade their neutralizing activity, leading to infection enhancement of Omicron. Our study provides up-to-date epitope information on SARS-CoV-2 variants to help design better vaccines or antibody-based therapeutics against future variants.

Epitope screening and vaccine molecule design of PRRSV GP3 and GP5 protein based on immunoinformatics

“…The study employed immunoinformatics methods to screen the gene source and identify immunoprotective epitopes that could enhance the affinity of protective antibodies and promote a balanced cellular immunity. The construction of candidate vaccines can effectively induce neutralizing antibodies that inhibit virus replication, kill infected cells and balance the effector T cells of the immune response 23 . Based on this, our team targeted the isolated PRRSV, GP3 and GP5 proteins and screened the dominant protective epitopes using immunoinformatics methods.…”

“…The construction of candidate vaccines can effectively induce neutralizing antibodies that inhibit virus replication, kill infected cells and balance the effector T cells of the immune response. 23 Based on this, our team targeted the isolated PRRSV, GP3 and GP5 proteins and screened the dominant protective epitopes using immunoinformatics methods. Furthermore, we concatenated the dominant epitope of the fusion GP3–GP5 protein as a candidate vaccine, which provides a feasible new solution for developing and preparing the PRRSV vaccine.…”

Simulation-Driven Design of Stabilized SARS-CoV-2 Spike S2 Immunogens

“…28 However, S2 apex epitopes elicit non-neutralizing antibodies, 26,27 which are dominant in the B cell population 27,38 and can interfere with binding of neutralizing antibodies. 39,40 This is also the case for other trimer interface epitopes in influenza HA 35 and human metapneumovirus (hMPV) F. 38 Hence, preventing the S2 trimer's apex opening may offer the foundations for the design of improved S2-based immunogens that may also afford binding and elicitation of quaternary epitope-specific antibodies.…”