Student Awarded

Ruth Kerubo Nyakundi

Ruth Kerubo Nyakundi

Country: Kenya

Project Title: Production of monoclonal antibodies to malaria antigens

Institution: Institute of Primate Research

Malaria continues to be a leading cause of morbidity and mortality in 91 countries in the tropical and subtropical regions of the world. In 2017, Plasmodium falciparum infections accounted for over 90% of the reported 219 million cases and 435,000 deaths caused by malaria parasites. With chemotherapy being the preferred control strategy and increasing documentation of drug resistance, development of an effective vaccine remains a major research goal. This study therefore proposes to generate human monoclonal antibodies that target P. falciparum RH5 (PfRH5) and PfAMA1 blood stage proteins from individuals naturally immune to malaria. Individual antigen-specific B cells will be sorted and the heavy and light chain variable regions of human IgG cloned in an expression vector to produce human antibodies. The generated antibodies will be tested to establish whether they recognize the protein of interest. If they recognize the protein of interest, we will examine whether these antibodies have the ability to block binding of proteins to it receptors on erythrocytes and inhibit parasite invasion in vitro. We will also determine whether PfRH5 and PfAMA1 correlate with reduced susceptibility to malaria infection or affected by multiple parasitism (particularly with helminth that are known to induce immune suppression) by measuring parasite specific antibody levels in plasma of pregnant women with or without malaria and helminth co-infections. We anticipate that PfRH5 and PfAMA1 will offer promising blood-stage malaria vaccine candidates as well as establish the role of co-infections in maintenance of specific antibody pools that may affect vaccine efficacy.

African Supervisor

Thomas Maina Kariuki

Thomas Maina Kariuki

African Host Country: Kenya

Institution: Institute of Primate Research

Laboratory: Department of Tropical and Infectious Diseases, Schistosomiasis and malaria program

Research in our lab focuses on schistosomiasis and malaria infection and utilizes non-human primates as models of human diseases. We seek to understand in depth the interactions between the host and parasite by studying clinical, parasitological, physiological and immunological parameters in NHPs and how these relate to human disease.

We have developed the Olive baboon as a model to study schistosomiasis (Schistosoma mansoni and S. haematobium) and malaria (Plasmodium knowlesi, that closely mimics P. falciparum infection in humans) infection. The baboon has served as a preclinical model for the development, testing for efficacy, immunogenicity and toxicity of both drugs, vaccine candidates and diagnostic tools.

In endemic areas individuals harbor more than one parasite and this will lead to poor vaccine outcomes. To dissect and understand the various processes, our research team undertakes malaria and schistosomiasis co-infection studies and are also assessing the effect of helminth infections on vaccine efficacy.

International Supervisor

Christopher Lee King

Christopher Lee King

International Host Country: United States of America

Institution: Case Western Reserve University

Laboratory: Center for Global Health and Diseases

Christopher L. King, MD, PhD, MPH received his advanced degrees from the University of Michigan, performed his internal medicine residency at New York University, Bellevue Medical Center in New York City, and completed his infectious diseases and post-doctoral training at the Laboratory of Parasitic Diseases at the National Institutes of Health (NIH), Bethesda, MD. He has been on the faculty Case Western Reserve University School Medicine since completing his training where he is currently a professor of International Health, Medicine and Pathology.  He is also a staff physician on the infectious disease consult service at the Veteran Affairs (VA) Medical Center in Cleveland. He studies mechanisms of acquired immunity and immunopathology of malaria, lymphatic filariasis and schistosomiasis.  A focus of his laboratory is to study human immune responses from people infected or exposed to infections from endemic countries.  He has published over 160 papers in peer reviewed journals and he has had continuous NIH and/or VA funding for almost 30 years to support his laboratory where he currently has technicians and post-doctoral PhD and/or MD fellows working the laboratory.