Designing Combinatorial Multiepitope Vaccine Candidates against Scrub Typus by a Proteome-wide Immunoinfomatics Approach.

Abstract

Scrub typhus (ST) is a mite-borne infection caused by the bacteria Orientia tsutsugamushi and a major public health concern in eastern and south eastern Asia. Early diagnosis and immediate intervention with antibiotics are required to limit the severity of the infection. Prophylaxis is compromised by the absence of an effective vaccine against O. tsutsugamushi. Development an effective vaccine is impeded due to extreme divergence of major surface antigens limiting cross-protectivity. Adopting a proteome-wide immunoinformatic approach, here, immunodominant outer membrane proteins are identified and conserved regions enriched in B-cell, Tc-cell, and Th-cell epitopes were mapped. Similarly, immunodominant stretches from salivary proteins of the vector were identified. Fifteen independent MEVs were designed by combining such segments and were analysed for physicochemical and immunological properties. Tertiary structure of the prioritized MEV was modelled, and interaction with TLR2, 4, and 5 was profiled through molecular docking and MD simulation. A glycosylation-deficient version of the MEV was also designed and analysed similarly. Both the MEVs were immune-simulated, which indicated elicitation of effective immune response. In silico cloning and expression were performed for bacterial and mammalian expression systems. Though the proteome-wide combinatorial approach with immunodominant segments demonstrated prospect, experimental validation for its efficacy against ST is warranted.