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James M. Burns Jr.

James M. Burns Jr., PhD

Professor


Department: Microbiology & Immunology

Education

  • PhD - Hahnemann University (1989)

James M. Burns Jr., PhD, 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, multi-stage vaccines.

Graduate student: Will Stump

Research associate: Amy Ott, PhD

Research Interests

Development of protective immunity against malaria induced by immunization with defined subunit vaccines targeting pre-erythrocytic stage, blood-stage and sexual stage parasites.

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 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.

Malaria image

Primary Interest

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 leading vaccine candidates to define highly efficacious, multi-antigen formulations and link antibody specificity and isotype with functional assays of parasite neutralization. We are targeting merozoite surface protein 2 (PfMSP2), reticulocyte-binding protein homologue 5 (PfRh5), the 25 kDa sexual stage antigen of P. falciparum (Pfs25) and most recently, the pre-erythrocytic stage circumsporozoite protein. Each is being produced as a single recombinant antigen and as a chimeric fusion protein with the rPfMSP8 (ΔAsn/Asp) carrier. We are comparing the immunogenicity of single versus chimeric antigen vaccines formulated with Th1/Th2 biasing adjuvants with respect to antibody titer, epitope specificity, isotype and activity in functional assays of parasite neutralization. In mice and non-human primates, we will test 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 PfCSP and Pfs25 and will be tested for their ability to block infection of hepatocytes and reduce transmission of sexual stage parasites back to mosquitoes respectively. Success in these efforts would 1) represent a major step toward the goal of producing a combined pre-erythrocytic-stage/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

Given the recent success in the development of mRNA-based vaccines, we are exploring this use of this platform for delivery of P. falciparum malaria vaccine candidates. These studies will build on the knowledge we have gained with recombinant antigen/adjuvant based multivalent vaccine formulations, with the use of PfMSP8 as a vaccine carrier.

Publications

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

"Inclusion of an optimized Plasmodium falciparum merozoite surface protein 2-based antigen in a trivalent, multi-stage malaria vaccine"
Eacret JS, Parzych EM, Gonzales DM and Burns JM Jr.
J. Immunol. 206: 1 (2021)

"Maintaining immunogenicity of blood-stage and sexual stage subunit malaria vaccines when formulated in combinations"
Parzych EM, Miura K, Long CA and Burns JM Jr.
PLoS One, 15:e0232355 (2020)

"Immunization with merozoite surface protein 2 fused to a Plasmodium-specific carrier protein elicits strain-specific and strain-transcending, opsonizing antibody"
Eacret JS, Gonzales DM, Franks RG and Burns JM Jr.
Scientific Reports, 9:9022 (2019)

"Evaluation of a Plasmodium-Specific Carrier Protein to Enhance Production of Recombinant Pfs25, a Leading Transmission-Blocking Vaccine Candidate"
Parzych EM, Miura K, Ramanathan A, Long CA and Burns JM Jr.
Infection and Immunity, 86:e00486-17 (2018)

"Immunogenicity of a chimeric Plasmodium falciparum merozoite surface protein vaccine in Aotus monkeys"
Burns JM Jr., Miura K, Sullivan J, Long CA and Barnwell JW
Malaria J. 15:159 (2016)

"Host erythrocyte environment influences the localization of exported protein 2, an essential component of the Plasmodium translocon"
Meibalan E, Comunale MA, Lopez AM, Bergman LW, Mehta A, Vaidya AB and Burns JM Jr.
Eukaryotic Cell. 14:371-384 (2015)

"A chimeric Plasmodium falciparum merozoite surface protein vaccine induces high titers of parasite growth inhibitory antibodies"
Alaro JR, Partridge A, Miura K, Diouf A, Lopez AM, Angov E, Long CA and Burns JM Jr.
Infection and Immunity Immun. 81:3843-3854 (2013)

"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 Burns JM Jr.
Malaria J. 11:265 (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 Burns JM 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 Burns JM 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 Burns JM Jr.
Infection and Immunity, 78:5151-5162 (2010)

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 Burns JM 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 Burns JM Jr.
Infection and Immunity, 75:1349 (2007)

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 Burns JM 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 JM Jr., Flaherty JM, Nanavati P and Weidanz WP
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 JM Jr., 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 JM Jr., Belk CC, and PD Dunn.
Infection and Immunity, Vol. 68: 6189 (2000)


Contact Information


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