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PEPTIDE VACCINES AGAINST MOSQUITO-BORNE RNA VIRUSES BASED ON BACTERIOPHAGE VIRUS-LIKE PARTICLES
Date of Award
Campus Access Dissertation
Doctor of Philosophy in Biochemistry and Molecular Biology (PhD)
Administrative Home Department
Department of Biological Sciences
Committee Member 1
Chandrashekar P. Joshi
Committee Member 2
Committee Member 3
Conventional vaccinology uses live attenuated viruses as well as inactivated viruses as vaccines. Live attenuated vaccines are very immunogenic and offer long lasting immunity to infectious agent but there cannot be used for everyone especially in patients with a compromised immune system. Inactivated vaccines are very safe and can be used to immunize everyone regardless of their immune status. However, unlike attenuated vaccines, their immune response is not long lasting. Given the limitations of conventional vaccinology, reverse vaccinology has recently been explored as an alternative approach to design safe and immunogenic vaccines against viral infections. Some regions in the envelope or the capsid of viruses have been predicted/shown to elicit neutralizing/protective antibodies against viruses. Reverse vaccinology is aimed at developing safe vaccines targeting only these regions (epitopes) on the envelope or the capsid of viruses. Although this approach is very safe, the epitopes (peptide antigens) used in developing these vaccines are less immunogenic due to the size, morphology, and the geometry of the peptide antigen in question. In this dissertation, I assessed the immunogenicity of peptide antigens derived from two mosquito-borne RNA virus, Zika virus (ZIKV) and Chikungunya virus (CHIKV), on a highly immunogenic bacteriophage platform known as virus-like particles (VLPs). Currently, there are no approved vaccines against ZIKV and CHIKV. In this dissertation, I showed that ZIKV and CHIKV peptides displayed on bacteriophage VLPs elicited high antibody titers even at a dose of 5 mg of the VLPs displaying the peptides. Additionally, sera from mice immunized with bacteriophage VLPs displaying ZIKV peptides neutralized ZIKV from infecting monkey kidneys cells. Bacteriophage VLPs is an excellent approach to enhance the immunogenicity of ZIKV and CHIKV peptide antigens. Because VLPs resemble viruses in terms of shape, size, morphology exception that, they lack the viral genome (do not replicate), there are excellent platforms to develop safe and effective peptide vaccines.
Basu, Rupsa, "PEPTIDE VACCINES AGAINST MOSQUITO-BORNE RNA VIRUSES BASED ON BACTERIOPHAGE VIRUS-LIKE PARTICLES", Campus Access Dissertation, Michigan Technological University, 2019.