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James M. Burns Jr.

James M. Burns Jr., PhD

Professor


Department: Microbiology & Immunology

Education

  • PhD - Hahnemann University (1989)

Dr. Jim Burns is a professor in the Department of Microbiology & Immunology at Drexel University College of Medicine.

Research Overview

The broad research interests of the lab include the host immune response to malaria parasites and the development of highly immunogenic, multi-subunit vaccines.

Graduate students: Elizabeth Parzych, Jacqueline Schneider
Research associate: Donna Gonzales

Research Interests

Development of protective immunity against blood-stage malaria induced by immunization with defined subunit vaccines.

Research

Illustration of experimental approach

Extensive studies in humans and animal models indicate that acquired immunity to malaria develops. Nevertheless, the goal of reducing malaria morbidity and mortality through active immunization has not been achieved. As such, Plasmodium falciparum malaria remains one of the most significant public health problems in the world today. The long-term goal of our research is to maximize the protective immunity against blood-stage malaria induced by immunization with defined subunit vaccines. We utilize the Plasmodium yoelii and Plasmodium chabaudi rodent models of malaria to gain in vivo experimental data on protective antigens and immune mechanisms. We apply these data to the investigation of human malaria in parallel in vitro studies of P. falciparum blood-stage parasites.

Primary Interest

Malaria image

The malaria vaccine development field has faced several challenges but two key issues have repeatedly emerged. First, the immunogenicity of subunit vaccines must be improved. Second, there is no indication that immunity to these complex, multi-stage plasmodial parasites is directed toward a single protective antigen. Vaccine candidate antigens will need to be formulated in combination, without any reduction in the immunogenicity of individual components. Our work focuses on vaccine targets where antibody-dependent mechanisms of immunity are essential, but where immunogenicity of neutralizing B cell epitopes has not been optimal. In proof-of-concept studies, we overcome obstacles related to both production and suboptimal immunogenicity of recombinant antigen based vaccines by engineering a well-conserved, highly immunogenic, P. falciparum-specific carrier protein that induces potent CD4+ T cell help for the production of neutralizing antibodies. Genetic fusion of neutralizing B cell epitopes of P. falciparum to a parasite-specific carrier protein will also allow concurrent boosting of vaccine-primed B cells and vaccine-primed CD4+ T cells by natural P. falciparum infection.

Malaria merozoites

In our main project, we are systematically evaluating four leading vaccine candidates to define highly efficacious, multi-antigen formulations and link antibody specificity and isotype with functional assays of parasite neutralization. We are working to express and purify recombinant merozoite surface protein 2 (PfMSP2), reticulocyte-binding protein homologue 5 (PfRh5) and the 25 kDa sexual stage antigen of P. falciparum (Pfs25), each as a single antigen and as a chimeric fusion protein with the rPfMSP8 (ΔAsn/Asp) carrier. We will compare the immunogenicity of single versus chimeric antigen vaccines formulated with Th1/Th2 biasing adjuvants with respect to antibody titer, isotype and activity in functional assays of parasite neutralization. In mice and non-human primates, we will test three, highly immunogenic recombinant vaccines in combined formulations with rPfMSP1/8, a chimeric MSP-based vaccine shown to elicit high titers of growth inhibitory antibodies. For antibodies elicited by PfMSP1, PfMSP2 and PfRh5 vaccines, the neutralization of extracellular, invasive merozoites by antibody in concert with complement and/or Fc receptor bearing phagocytic cells will be key. In contrast, antibodies to Pfs25 will be tested for their ability to block transmission of sexual stage parasites back to mosquitoes. Success in these efforts would 1) represent a major step toward the goal of producing a combined blood-stage/sexual-stage malaria vaccine to concurrently reduce the severity of clinical disease and block transmission and 2) provide a solid foundation for subsequent safety and immunogenicity testing in human subjects.

Secondary Interest

CD4+ T cells contribute to both antibody-dependent and antibody-independent immunity during blood-stage malaria, but have not been specifically targeted for vaccine development. In part, this is due to i) the lack of a comprehensive analysis on the most relevant epitopes/antigens to include and ii) the need to concurrently and efficiently prime CD4+ T cells which recognize multiple parasite proteins. As a first step, we are interested in identifying plasmodial peptides bound to MHC class II molecules displayed on splenic antigen presenting cells during acute blood-stage malaria We will approach this epitope identification using mass spectrometry. We expect that immunization with a subset of these T cell epitopes can prime IFNγ, producing CD4+ T cells of diverse specificities to enhance clearance of blood-stage parasites during acute malaria. These proof of concept studies will be conducted in the Plasmodium yoelii murine model of malaria to provide a rationale and clear path to advance the development and testing of a comparable P. falciparum based vaccine component.

Publications

Selected Publications
(See all James M. Burns' publications in PubMed.)

"Remarkable stability in patterns of blood-stage gene expression during episodes of non-lethal Plasmodium yoelii malaria"
Cernetich-Ott A, Daly TM, Vaidya AB, Bergman LW, and JM Burns, Jr
Malaria J., in press. 2012.

"Evaluation of the immunogenicity and vaccine potential of recombinant Plasmodium falciparum merozoite surface protein 8"
Alaro JR, Angov E, Lopez AM, Zhou H, Long CA, and JM Burns, Jr
Infect. Immun., 80: 2473-2484, 2012.

Protective immune responses elicited by immunization with a chimeric blood-stage malaria vaccine persist but are not boosted by Plasmodium yoelii challenge infection.
Alaro JA, Lynch MM and JM Burns Jr.
Vaccine, 28: 6876-6884, 2010.

Elevated levels of the Plasmodium yoelii homologue of macrophage migration inhibitory factor reduce the severity of blood-stage malaria. 
Thorat, S, Daly TM, Bergman LW, and JM Burns Jr.
Infection and Immunity, 78: 5151-5162, 2010.

Prediction of merozoite surface protein 1 and apical membrane antigen 1 vaccine efficacy against Plasmodium chabaudi malaria based on prechallenge antibody responses. 
Lynch, MM, Cernetich-Ott A, Weidanz WP and JM Burns Jr.
Clinical and Vaccine Immunology, 16:293-302, 2009.

Suppression of lethal Plasmodium yoelii malaria following protective immunization requires antibody-, IL-4-, and IFN-γ-dependent responses induced by vaccination and/or challenge infection. 
Petritus PM and JM Burns Jr.
The Journal of Immunology, 180: 444, 2008.

Enhanced protection against malaria by a chimeric merozoite surface protein vaccine. 
Shi Q, Lynch MM, Romero M, and JM Burns Jr.
Infection and Immunity, 75: 1349, 2007.

Expression, localization and erythrocyte binding activity of Plasmodium yoelii merozoite surface protein-8. 
Shi Q, Cernetich-Ott A, Lynch MM, and JM Burns Jr.
Molecular and Biochemical Parasitology, 149: 231, 2006.

Alteration in host cell tropism limits the efficacy of immunization with a surface protein of malaria merozoites.
Shi Q, Cernetich A, Daly TM, Galvan G, Vaidya AB, Bergman LW, and JM Burns Jr.
Infection and Immunity, 73: 6363, 2005.

Protection against Plasmodium chabaudi malaria induced by immunization with apical membrane antigen-1 and merozoite surface protein-1 does not require IFN-γ or IL-4.
Burns Jr., JM, Flaherty JM, Nanavati P, and WP Weidanz.
Infection and Immunity, 72: 5605, 2004.

Immunization against Plasmodium chabaudi malaria using combined formulations of apical membrane antigen-1 and merozoite surface protein-1. 
Burns Jr., JM, Flaherty PR, and WP Weidanz.
Vaccine, 21: 1843, 2003.

A protective GPI-anchored membrane protein of Plasmodium yoelii trophozoites and merozoites contains two epidermal growth factor-like domains. 
Burns Jr., JM, Belk CC, and PD Dunn.
Infection and Immunity, Vol. 68, No. 11, November 2000.

Infection and I  An unusual tryptophan-rich domain characterizes two secreted antigens of Plasmodium yoelii infected erythrocytes. 
Burns Jr., JM, Adeeku EK, Belk CC, and PD Dunn
Molecular and Biochemical Parasitology, 110: 11, 2000.

Protective immunity against Plasmodium yoelii malaria induced by immunization with particulate blood-stage antigens.
Burns Jr., JM, Dunn PD, and DM Russo.
Infection and Immunity, 65: 3138, 1997.

Protective immunization with a novel membrane protein of Plasmodium yoelii - infected erythrocytes. 
Burns Jr., JM, Adeeku EK, and PD Dunn.
Infection and Immunity, 67: 675, 1999


Contact Information


Research Office

Department of Microbiology & Immunology
2900 W. Queen Lane
Philadelphia, PA 19129
Phone: 215.991.8490
Fax: 215.848.2271