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In-silico vaccine construction: targeting HPV major capsid L1 protein

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BRAC University

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Abstract

Cervical cancer is a prevalent outcome of human papillomavirus (HPV) infection, which continues to be a major global health concern. Utilizing virus-like particles (VLPs) based on L1 proteins is one of the methods used to battle HPV and has showed promise in the creation of vaccines. Currently, genotype-restricted protection is provided through commercially available vaccines like Gardasil and Cervarix. However, there are significant obstacles to the equitable distribution of these vaccinations to developing countries, principally because of financial limitations. Therefore, the creation of next-generation high-risk HPV vaccines is urgently needed. In this thorough analysis, we have created DNA constructs, mostly based on the L1 genes, that display significant conservation among high-risk HPV strains and have the potential to be immunogenic. The following fundamental components make up our analytical framework: (1) B-cell epitope mapping; (2) CD4+ and CD8+ T-cell epitope mapping; (3) allergenicity evaluation; (4) biochemical analysis; (5) molecular docking studies; (6) 3D modeling; and (7) data gathering, analysis, and the creation of L1 and L2 DNA constructs. Additionally, our in vivo research has shown that L1 DNA constructs can trigger powerful immune responses when given in combination with the right adjuvants or delivery methods. The DNA structures that we have created are excellent candidates for HPV vaccinations that might provide broader protection against high-risk HPV strains. This study emphasizes the significance of ongoing efforts in the development of novel vaccine methods and marks a significant step towards tackling the global burden of HPV-related diseases.

Description

Cataloged from the PDF version of thesis.
Includes bibliographical references (pages 47-50).
This thesis is submitted in partial fulfillment of the requirements for the degree of Bachelor of Pharmacy, 2024.

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Thesis