Designing a multi-epitope vaccine against Peptostreptococcus anaerobius based on an immunoinformatics approach

Peptostreptococcus anaerobius is an anaerobic bacterium,which has been found selectively en-riched in the fecal and mucosal microbiota of colorectal cancer(CRC)patients.Emerging evidence suggest P.anaerobius may contribute to the development of CRC in human.In this study,we designed a multi-epitope chimeric vaccine against P.anaerobius PCWBR2,a recently identified adhesin that interacts directly with colon cell lines by bindingα2/β1 integrin frequently overexpressed in human CRC tumors and cell lines.Immunoinformatics tools predicted six cytotoxic T lymphocyte epitopes,five helper T lymphocyte epitopes,and six linear B lymphocyte epitopes.The predicted epitopes were joined with AAY or GPGPG linkers and a previously reported TLR4 agonist was added to the vaccine construct’s N terminal as an adjuvant using EAAAK linkers and the order of epitopes was optimized.Further in silico analysis revealed that the vaccine construct possesses satisfactory antigenicity,allergenicity,solubility,physicochemical properties,adjuvant-TLR4 molecular docking,and immune profile characteristics.Our study provided a promising design for vaccines against P.anaerobius.

AXIN1 boosts antiviral response through IRF3 stabilization and induced phase separation

Axis inhibition protein 1(AXIN1),a scaffold protein interacting with various critical molecules,plays a vital role in determining cell fate.However,its impact on the antiviral innate immune response remains largely unknown.Here,we identify that AXIN1 acts as an effective regulator of antiviral innate immunity against both DNA and RNA virus infections.In the resting state,AXIN1 maintains the stability of the transcription factor interferon regulatory factor 3(IRF3)by preventing p62-mediated autophagic degradation of IRF3.This is achieved by recruiting ubiquitin-specific peptidase 35(USP35),which removes lysine(K)48-linked ubiquitination at IRF3 K366.Upon virus infection,AXIN1 undergoes a phase separation triggered by phosphorylated TANK-binding kinase 1(TBK1).This leads to increased phosphorylation of IRF3 and a boost in IFN-I production.Moreover,KYA1797K,a small molecule that binds to the AXIN1 RGS domain,enhances the AXIN1-IRF3 interaction and promotes the elimination of various highly pathogenic viruses.Clinically,patients with HBV-associated hepatocellular carcinoma(HCC)who show reduced AXIN1 expression in pericarcinoma tissues have low overall and disease-free survival rates,as well as higher HBV levels in their blood.Overall,our findings reveal how AXIN1 regulates IRF3 signaling and phase separation-mediated antiviral immune responses,underscoring the potential of the AXIN1 agonist KYA1797K as an effective antiviral agent.