Identification of Vaccine Candidates Against Falciparum Malaria Using Genes with Tandem Repeats

Robidoux, Annalise

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Year:: 2022
Contributor:: Robidoux, Annalise (creator); Nixon, Christian (Reader); Wu, Hannah (Reader); Raj, Diapk (Advisor); Brown University. Biology and Medicine: Pathobiology (sponsor)
Genre:: theses
Subject:: Malaria; Malaria vaccine; vaccine design
Extent:: 6, 72 p.

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Abstract:: Objective: There are 240 million cases of malaria each year, making it one of the most endemic diseases in modern history. However, not substantial preventative measures have been identified. Current research effort focuses on the development of new vaccines. More than 40% of the vaccine candidates identified in the malaria parasite have tandem repeats in their genes. The current research project focuses on identifying vaccine targets utilizing in silico analysis of P. falciparum genes with tandem repeats. Methods: The P. falciparum genome was scanned for genes that contained tandem repeats. These genes were further down selected using in silico analysis for antigen prediction. Software tools like B-cell & T-cell epitopes, regions of hydrophilicity, low complexity, MHC II binding epitopes, protein 3D structure, low genetic diversity, trans membrane domain and signal peptides. Twenty-nine fragments were identified, and eleven fragments were inserted into a DNA vaccine vector pVR2001, immunized into mice. Polyclonal antibodies were harvested, and the efficacy of each antigen was evaluated using growth inhibition assays (GIAs). Results: Two of the eleven anti-sera were found to inhibit P. falciparum growth in culture with various degrees (75-98%). These two anti-sera were able to significantly inhibit the parasite in GIA and recognize proteins of the appropriate size from protein extracts from the parasite. Conclusions: This investigation found that reverse vaccine identification techniques were able to identify potential vaccine targets. Out of the eleven antigens used to vaccinate mice, two were found to have the potential to be used as a vaccine against falciparum malaria.
Notes:: Thesis (Sc. M.)--Brown University, 2022

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Citation

Robidoux, Annalise, "Identification of Vaccine Candidates Against Falciparum Malaria Using Genes with Tandem Repeats" (2022). Pathobiology Theses and Dissertations. Brown Digital Repository. Brown University Library. https://repository.library.brown.edu/studio/item/bdr:tfpfkrrr/

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Pathobiology Theses and Dissertations

Theses and Dissertations for the Pathobiology department.
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