Custommune: a web tool to design personalized and population-targeted vaccine epitopes

Abstract

Computational prediction of immunogenic epitopes is a promising platform for therapeutic and preventive vaccine design. A potential target for this strategy is human immunodeficiency virus (HIV-1), for which, despite decades of efforts, no vaccine is available. In particular, a therapeutic vaccine devised to eliminate infected cells would represent a key component of cure strategies. HIV peptides designed based on individual viro-immunological data from people living with HIV/AIDS have recently shown able to induce post-therapy viral set point abatement. However, the reproducibility and scalability of this method is curtailed by the errors and arbitrariness associated with manual peptide design as well as by the time-consuming process. We herein introduce Custommune, a user-friendly web tool to design personalized and population-targeted vaccines. When applied to HIV-1, Custommune predicted personalized epitopes using patient specific Human Leukocyte Antigen (HLA) alleles and viral sequences, as well as the expected HLA-peptide binding strength and potential immune escape mutations. Of note, Custommune predictions compared favorably with manually designed peptides administered in a recent phase II clinical trial (NCT02961829). Furthermore, we utilized Custommune to design preventive vaccines targeted for populations highly affected by COVID-19. The results allowed the identification of peptides tailored for each population and predicted to elicit both CD8+ T-cell immunity and neutralizing antibodies against structurally conserved epitopes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Overall, our data describe a new tool for rapid development of personalized or population-based immunotherapy against chronic and acute viral infections.

In Silico and In Vivo Evaluation of SARS-CoV-2 Predicted Epitopes-Based Candidate Vaccine

“…In addition, RBD was founded to interact with ACE2 glycosylated interface in a pattern that could explain the antiviral effect of some compounds against SARS-CoV-2. In addition, two S-glycoprotein residues namely Gly416 and Lys417 were computationally identified to be responsible for the interaction with the N-acetylglucosamine (NAG) moiety, this observation had led to identification of another binding critical region within SARS-CoV-2 RBD [13]. These binding-essential and cleavage-essential segments have been identified as regions covering continuous sequences on the spike glycoprotein including; RBDg (397-437), RBDp (455-502) and TMPRSS2 Cleavage site in the S2 (802-816).…”

“…Certain regions of SARS-CoV and SARS-CoV-2 receptor binding domain (RBD) could provide strong potential vaccine targets for a more specialized immune response against binding-critical portions of the RBD [5]. These binding and cleavage-essential segments have been previously identified as regions covering continuous sequences on the spike glycoprotein including RBDp (455-502), RBDg (397-437), furin cleavage site in the S1/S2 (676-690) and TMPRSS2 cleavage site in the S2 region (802-816) [13,14].…”

Immunogenicity of personalized dendritic-cell therapy in HIV-1 infected individuals under suppressive antiretroviral treatment: interim analysis from a phase II clinical trial

“…After MDDCT administration, NetMHCpan predictions were reanalyzed using the newly developed Custommune software [49]), which is validated based on documented biological data from the Los Alamos database [50]). The results were used to stratify patients' ex-post based on the concordance between software predictions [51].…”

“…custo mmune. com; [51]). This software is based on peptide affinity calculations and selects only those peptides in positions corresponding to epitopes validated by biological data for the matched HLA.…”

Immunogenicity of Personalized Dendritic-cell Therapy in HIV-1 Infected Individuals Under Suppressive Antiretroviral Treatment: Interim Analysis From a Phase II Clinical Trial.

“…To understand the correlates of viral DNA abatement, we then analyzed the accuracy of the predictions of NetMHCpan using a newly developed software (Custommune: www.custommune.com; (51)). This software is based on peptide a nity calculations and selects only those peptides in positions corresponding to epitopes validated by biological data for the matched HLA.…”