Graduation Year
2023
Document Type
Thesis
Degree
M.S.P.H.
Degree Name
MS in Public Health (M.S.P.H.)
Degree Granting Department
Global Health
Major Professor
Francis Ntumngia, Ph.D.
Committee Member
Jesper Madsen, Ph.D.
Committee Member
Iset Vera, Ph.D.
Keywords
Antibody, Subdomain, ELISA, Malaria
Abstract
Malaria, caused by the apicomplexan Plasmodium spp. , is a major public health issue that impacts over one-third of the world’s population ,with Plasmodium vivax accounting for over 130 million clinical cases annually. The circumsporozoite protein (CSP) is the most abundant molecule on the surface of Plasmodium sporozoites and is considered a leading pre-erythrocytic stage vaccine candidate. CSP is essential for sporozoite maturation, migration, and invasion. Anti-CSP antibodies interrupt sporozoite migration and infection of hepatocytes thus reducing liver-stage burden. P. vivax CSP is composed of three subdomains: a highly polymorphic immunodominant central repeat region (CRR), conserved N-terminal ,and C-terminal subdomains. Based on the highly polymorphic nature of the CRR, two major allelic variations of CSP, VK210 and VK247, have been identified in endemic regions. The immunodominant central repeat region is the major target of neutralizing antibodies. Inhibitory antibodies specific to the immunodominant epitopes of the two major vivax CSP allelic variants lack cross reactivity, posing a significant challenge in developing a broadly neutralizing, strain transcending CSP-based vaccine, which is why the non-repeat subdomains of CSP need to be explored for epitopes that elicit an antibody response. We hypothesize that the N- and C-terminals domains may contain epitopes of broadly neutralizing antibody responses. This study evaluates the immunogenicity of P. vivax CSP using naturally acquired antibodies from an endemic region of Thailand. The humoral immune response of serum samples from 49 P. vivax infected Thai patients against recombinant full-length CSP or its non-repeat subdomains (individually and in combination) were evaluated by indirect ELISA. The full-length protein was the most reactive with the sera followed by the N+C and C-terminal while the N-terminal protein was the least reactive. The identification and characterization of these immune epitopes is crucial for the development of a strain-transcending, broadly-neutralizing vaccine as it will guide epitope selection for inclusion in a CSP-based vaccine against P. vivax malaria.
Scholar Commons Citation
Esquenazi, Jack, "Evaluation of the Humoral Immune Responses to Plasmodium vivax Circumsporozoite Protein (CSP)-based Pre-Erythrocytic Vaccine Candidates" (2023). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/10111
