Carole A. Long, Ph.D.
Chief, Malaria Immunology Section
Director, PATH Malaria Vaccine Initiative Growth Inhibition Assay–Reference Center
Dr. Long received her Ph.D. in microbiology and immunology from the University of Pennsylvania and also did post-doctoral training there. Before joining NIAID in 1999, Dr. Long was a professor of microbiology and immunology at Hahnemann University School of Medicine (now Drexel University) in Philadelphia, Pennsylvania. She has served as president of the American Society for Tropical Medicine and Hygiene and chair of the Tropical Medicine and Parasitology Study Section. Her lab’s work focuses on innate and adaptive immune responses to malaria parasites. These immune responses are explored in rodent model systems and in children and adults living in malaria-endemic areas.
Description of Research Program
Research in the Malaria Immunology Section focuses on analysis of the interface between the erythrocytic stage of parasite infection and the immune system of the vertebrate host. This includes both innate and adaptive immune responses to malaria infection, as well as responses to immunization with specific malaria vaccine candidates. We are studying these host-parasite interactions in children and adults living in endemic areas and in rodent models of malaria. Major areas of investigation include the following:
- Characterizing innate immune responses to malaria parasites using murine models and samples collected from children and adults living in malaria-endemic areas
- Evaluating CD4+ T-cell responses to specific malaria antigens, including definition of various T-cell subpopulations (multifunctional T cells, memory T cells, etc.) and their effector functions in mice and in humans
- Determining quantitative and functional aspects of antibodies to blood-stage malaria parasite proteins, both in preclinical studies in animals and in children and adults living in malaria-endemic areas
- In addition, these antibodies are being used as part of a proteomics approach to identify novel vaccine candidates.
- Development, standardization, and application of the Growth Inhibition Assay (GIA) in the GIA–Reference Center (GIA-RC), a collaborative resource available to malaria researchers worldwide funded by a grant from the PATH-Malaria Vaccine Initiative
- The GIA is used to assess whether antibodies are capable of inhibiting malaria parasite invasion and growth in vitro and to assess functional activities of animal and human antibodies against blood-stage Plasmodium falciparum parasites.
- Collaborative studies in malaria immunology in association with Drs. Rick Fairhurst and Mahamadou Diakite at the Malaria Research and Training Center in Bamako, Mali
- Collaborative studies on malaria proteins and immune responses to them with Drs. Sanjay Singh and Subhash Singh at Gennova Biopharmaceuticals in Pune, India
Images
A) Schematic of a Plasmodium falciparum merozoite highlighting merozoite proteins that are potential vaccine candidates and B) Stepwise schematic of the invasion of a P. falciparum merozoite into an uninfected erythrocyte (A.F. Cowman et al. FEBS Letters. 2000;476:84-8.)
A transmission electron micrograph of a Plasmodium falciparum merozoite into an uninfected erythrocyte (Source unknown)
In vitro parasite growth inhibition assay to assess functional activity of antibodies to merozoite antigens
CD4+ T cell cytokine responses are allele-specific. Specificity of CD4+ T-cell responses of peripheral blood mononuclear cells from malaria-naïve volunteers immunized with P. falciparum MSP142-FVO formulated on Alhydrogel (A and B) and MSP142-3D7 formulated on Alhydrogel (C and D). (Huaman MC et al. J Immunol. 2008 Feb 1;180(3):1451-61)
Research Group Members
Standing: Ababacar Diouf, Cecilia Huaman, Gregory Tullo, Carole Long, Samuel Moretz, Hong Zhou
Kneeling: Reid Harvey, Christiana Fogg, Allison Gionta, Kate Smigiel
Not pictured: Eugene Oteng
Selected Recent Publications
To view a complete listing, visit PubMed.
Miura K, Zhou H, Moretz SE, Diouf A, Thera MA, Dolo A, Doumbo O, Malkin E, Diemert D, Miller LH, Mullen GE, Long CA. Comparison of biological activity of human anti-apical membrane antigen-1 antibodies induced by natural infection and vaccination. J Immunol. 2008 Dec 15;181(12):8776-83.
Huaman C, Martin LB, Malkin E, Narum DL, Miller LH, Mahanty S, Long CA. Ex vivo cytokine and memory T cell responses to the 42-kDa fragment of Plasmodium falciparum merozoite surface protein-1 in vaccinated volunteers. J Immunol. 2008 Feb 1;180(3):1451-61.
Miura K, Zhou H, Muratova OV, Orcutt AC, Giersing B, Miller LH, Long CA. In immunization with Plasmodium falciparum apical membrane antigen 1, the specificity of antibodies depends on the species immunized. Infect Immun. 2007 Dec;75(12):5827-36.
Dicko A, Diemert DJ, Sagara I, Sogoba M, Niambele MB, Assadou MH, Guindo O, Kamate B, Baby M, Sisoko M, Malkin EM, Fay MP, Thera MA, Miura K, Dolo A, Diallo DA, Mullen GE, Long CA, Saul A, Doumbo O, Miller LH. Impact of a Plasmodium falciparum AMA1 vaccine on antibody responses in adult Malians. PLoS ONE. 2007 Oct 17;2(10):e1045.
Malkin E, Long CA, Stowers AW, Zou L, Singh S, MacDonald NJ, Narum DL, Miles AP, Orcutt AC, Muratova O, Moretz SE, Zhou H, Diouf A, Fay M, Tierney E, Leese P, Mahanty S, Miller LH, Saul A, Martin LB. Phase 1 study of two merozoite surface protein 1 (MSP1(42)) vaccines for Plasmodium falciparum malaria. PLoS Clin Trials. 2007;2(4):e12.
Singh S, Miura K, Zhou H, Muratova O, Keegan B, Miles A, Martin LB, Saul AJ, Miller LH, Long CA. Immunity to recombinant plasmodium falciparum merozoite surface protein 1(MSP1): protection in Aotus nancymai monkeys strongly correlates with anti-MSP1 antibody titer and in vitro parasite-inhibitory activity. Infect Immun. 2006 Aug;74(8):4573-80.
Mullen GE, Giersing BK, Ajose-Popoola O, Davis HL, Kothe C, Zhou H, Aebig J, Dobrescu G, Saul A, Long CA. Enhancement of functional antibody responses to AMA1-C1/Alhydrogel, a Plasmodium falciparum malaria vaccine, with CpG oligodeoxynucleotide. Vaccine. 2006 Mar 24;24(14):2497-505.
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