Thioredoxin is a low molecular weight redox-active protein of filarial parasite that plays a crucial role in downregulating the host immune response to prolong the survival of the parasite within the host body. It has the ability to cope up with the oxidative challenges posed by the host. Hence, the antioxidant protein of the filarial parasite has been suggested to be a useful target for immunotherapeutic intervention of human filariasis. In this study, we have designed a multi-epitope peptide-based vaccine using thioredoxin of Wuchereria bancrofti. Different MHC-I and MHC-II epitopes were predicted using various web servers to construct the vaccine model as MHC-I and MHC-II epitopes are crucial for the development of both humoral and cellular immune responses. Moreover, TLRs specific adjuvants were also incorporated into the vaccine candidates as TLRs are the key immunomodulator to execute innate immunity. Protein-protein molecular docking and simulation analysis between the vaccine and human TLR was performed. TLR5 is the most potent receptor to convey the vaccine-mediated inductive signal for eliciting an innate immune response. A satisfactory immunogenic report from an in-silico immune simulation experiment directed us to propose our vaccine model for experimental and clinical validation. The reverse translated vaccine sequence was also cloned in pET28a(+) to apply the concept in a wet lab experiment in near future. Taken together, this in-silico study on the design of a vaccine construct to target W. bancrofti thioredoxin is predicted to be a future hope in saving human-being from the threat of filariasis.
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http://dx.doi.org/10.1016/j.meegid.2022.105237 | DOI Listing |
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