Identification of Potential Malaria Vaccine Antigens by Exploiting Naturally Acquired Immunity

Date/Time: 08 May 2013, 12:00 PM - 1:00 PM
Speaker: Ruobing Wang, M.D., Ph.D.
Speaker Affiliation: Associate Professor, Seattle BioMed; Affiliate Associate Professor, Departments of Pathobiology & Global Health, University of Washington, Seattle, WA
Venue: John A. Burns School of Medicine, Kakaako, MEB Auditorium (Room 315)

For more info: Cori Watanabe (808) 692-1654
Description: Malaria remains one of the most prevalent and lethal human infectious diseases worldwide. Evidence suggests that antimalarial T cells eliminate liver stage parasites, whereas antibodies eliminate blood stage parasites. However, no single Ag tested in humans can completely prevent infection, suggesting that multistage/multivalent vaccines may be required for complete protection. Leveraging Plasmodium genomics, bioinformatics, and reverse vaccinology, we are developing platforms to select optimal pre-erythrocytic and erythrocytic stage Ags for malaria intervention.

By comparing the IFN-y responses of PBMCs from P. vivax-exposed and control donors to 100 P. vivax bioinformatically-selected candidate Ags, we identified 22 Ags that were recognized mainly by donors with naturally acquired immunity. Some Ags were recognized only by PBMCs of Duffy-negative (Fy-) donors and may be liver stage-specific, whereas others were preferentially recognized by Fy(+) donors and may be blood-stage or multi-stage Ags. DNA vaccines encoding 4 of 19 P. yoelii orthologs tested significantly reduced liver stage burdens and partially sterile protection in mice challenged with P. yoelii sporozoites.

To identify novel Ags associated with anti-disease immunity, we constructed a proteome array containing ~4,500 Pf and Pv blood stage proteins and screened the arrays with sera from symptomatic or asymptomatic children infected with Pf, Pv or both. Using a machine-learning algorithm, we discovered Abs to 45 proteins that differed between asymptomatic and symptomatic children. These proteins may play critical roles in protection against blood stage parasites and are potential vaccine candidates for disease control.

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