Application of immunoinformatics to develop a novel and effective multiepitope chimeric vaccine against Variovorax durovernensis

Abstract

Bloodstream infections pose a significant public health challenge caused by resistant bacteria such as Variovorax durovernensis, a recently reported Gram-negative bacterium, worsening the burden on healthcare systems. The design of a vaccine using chimeric peptides derived from a representative V. durovernensis strain holds significant promise for preventing disease onset. The current study aimed to employ reverse vaccinology (RV) approaches such as the retrieval of V. durovernensis proteomics data, removal of redundant proteins by CD-HIT, filtering of non-homologous proteins to humans and essential proteins, identification of outer membrane (OM) proteins by CELLO and PSORTb. Following these steps immunoinformatic approaches were applied, such as epitope prediction by IEDB, vaccine design using linkers and adjuvant and analysis of antigenicity, allergenicity, safety and stability. Among the 4208 nonredundant proteins, an OmpA family protein (A0A940EKP4) was designated a potential candidate for the development of a multiepitope vaccine construct. Upon analysis of OM protein, six immunodominant (B cell) epitopes were found on the basis of the chimeric construct following the prediction of CTL stands cytotoxic T lymphocyte and HTL stands helper T lymphocyte epitopes. To ensure comprehensive population coverage globally, the CTL and HTL coverage rates were 58.18 % and 46.56 %, respectively, and 77.23 % overall. By utilizing EAAAK, GPGPG, and AAY linkers, Cholera toxin B subunit adjuvants, and appropriate epitopes were smoothly incorporated into a chimeric vaccine effectively triggering both adaptive and innate immune responses. For example, the administered antigen showed a peak in counts on the fifthday post injection and then gradually declined until the fifteenth day. Elevated levels of several antibodies (IgG + IgM > 700,000; IgM > 600,000; IgG1 + IgG2; IgG1 > 500,000) were observed as decreased in the antigen concentration. Molecular dynamics simulations carried out via iMODS revealed strong correlations between residue pairs, highlighting the stability of the docked complex. The designed vaccine has promising potential in eliciting specific immunogenic responses, thereby facilitating future research for vaccine development against V. durovernensis.