Identification and Analysis of Unstructured, Linear B-Cell Epitopes in SARS-CoV-2 Virion Proteins for Vaccine Development

Abstract

The efficacy of SARS-CoV-2 nucleic acid-based vaccines may be limited by proteolysis of the translated product due to anomalous protein folding. This may be the case for vaccines employing linear SARS-CoV-2 B-cell epitopes identified in previous studies since most of them participate in secondary structure formation. In contrast, we have employed a consensus of predictors for epitopic zones plus a structural filter for identifying 20 unstructured B-cell epitope-containing loops (uBCELs) in S, M, and N proteins. Phylogenetic comparison suggests epitope switching with respect to SARS-CoV in some of the identified uBCELs. Such events may be associated with the reported lack of serum cross-protection between the 2003 and 2019 pandemic strains. Incipient variability within a sample of 1639 SARS-CoV-2 isolates was also detected for 10 uBCELs which could cause vaccine failure. Intermediate stages of the putative epitope switch events were observed in bat coronaviruses in which additive mutational processes possibly facilitating evasion of the bat immune system appear to have taken place prior to transfer to humans. While there was some overlap between uBCELs and previously validated SARS-CoV B-cell epitopes, multiple uBCELs had not been identified in prior studies. Overall, these uBCELs may facilitate the development of biomedical products for SARS-CoV-2.

Screening and identification of B cell epitope of the nucleocapsid protein in SARS-CoV-2 using the monoclonal antibodies

“…Epitopes are the basis of protein antigenicity, and they act a vital part in the preparation of specific antibodies against proteins, the computer-aided design of vaccines, especially in the recent tumor immunotherapy (Corral-Lugo et al 2020 ). Epitopes are divided into linear epitopes and conformational epitopes.…”

Cross-Recognition of SARS-CoV-2 B-Cell Epitopes with Other Betacoronavirus Nucleoproteins

“…In contrast to S, N protein does not play direct role in viral attachment to epithelial cells of the upper and lower respiratory tracts so that anti-N antibodies are neither neutralizing nor protective against SARS-CoV in animal models [ 28 ]. In addition, this protein is ten-fold more abundant than S protein in the virion [ 29 ], very immunogenic [ 30 ], and extraordinarily enriched in flexible loops carrying validated and predicted B-cell epitopes [ 31 ]. Moreover, N protein is highly conserved among coronaviruses, probably due to high selective pressure to maintain numerous interactions with RNA in addition to viral and host proteins required by its role in virulence [ 32 ].…”

“…Sequences were aligned by Muscle 3.8 [ 35 ]. Linear B-cell epitopes were predicted in SARS-CoV-2 structural sequences as described elsewhere [ 31 ]. Transmembrane helices were predicted with Phobius [ 36 ] and not considered to define B-cell epitopes since they are buried, i.e., not accessible, in the membrane.…”

Designing Multi-Antigen Vaccines Against Acinetobacter baumannii Using Systemic Approaches

“…baumannii therefore epitomizes microorganisms that require alternatives to small molecule-based antimicrobial therapy (10). Multiple studies have reported protective immunity against A. baumannii after prophylactic vaccination or administration of antibodies in rodent infection models (reviewed in (11)). These preclinical results suggest that prophylatic vaccination and passive therapeutics could contribute to the prevention and treatment of infections caused by this pathogen.…”

“…A monoclonal antibody against the A. baumannii capsular polysaccharide was able to rescue infected mice in a lethal sepsis model (12). Candidates that have been tested in preclinical vaccine models include the OmpA porin (13), Ata (14) and Bap (15), and more recently BamA (16) and Omp22 (17) among others (11). However, many of these candidates provide only partial protection against infection, as exemplified by vaccination with the OmpA porin (13).…”