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Carole A. Long, Ph.D.
Twinbrook III, Room 3W13
12735 Twinbrook Parkway Rockville, MD 20852-8132​
Phone: 301-496-3655
Fax: 301-443-5778
clong@niaid.nih.gov

Laboratory of Malaria and Vector Research

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Carole A. Long, Ph.D.

Photo of Carole A. Long, Ph.D.

Chief, Malaria Immunology Section, LMVR
Director, PATH Malaria Vaccine Initiative Growth Inhibition Assay–Reference Center

Major Areas of Research

  • Studying the acquisition of immunity to malaria in those living in malaria-endemic areas
  • Investigating the process of transmission of malaria in the field
  • Identifying and evaluating possible new malaria vaccine candidates, focusing on the erythrocytic and sexual stages of malaria infection
  • Standardization and application of an in vitro parasite growth inhibition assay (GIA) and a mosquito membrane feeding assay (MFA) for testing antibodies to Plasmodium falciparum erythrocytic and sexual stages, respectively
 

Program Description

Research in the Malaria Immunology Section focuses on analysis of the interface between the malaria parasite and the immune system of the vertebrate host. It is known that those living in malaria-endemic areas progressively acquire resistance to this infection, although this takes many years to attain. We have also known that pioneering studies going back to the early 1960s have established that antibodies from adults in endemic areas, when passively transferred to children with malaria, can drive down parasitemias. However, we still do not know the antigenic targets of those antibodies, nor do we know the effector mechanisms involved in the reduction of parasite burdens. In addition, we have only limited knowledge of the parasite sexual stages and their transmission through mosquitoes in the field. Our studies are directed toward a better understanding of these complex and important parasites, as well as identification and evaluation of possible candidate antigens for a malaria vaccine.

We are studying the acquisition of clinical immunity in children living in malaria-endemic areas and investigating the impact of hemoglobin polymorphisms such as sickle cell trait on malaria incidence and disease. We have a long-standing collaboration with investigators in Mali, and in 2008, we established a new field site in Kenieroba, Mali. We are characterizing malaria-specific antibody responses in children and adults to both erythrocytic and sexual stages of parasite development. Antibodies to these stages are being characterized for their functional activity against parasites using a number of different assays. Moreover, these assays are being used to evaluate various parasite-encoded proteins as potential malaria vaccine candidates.

Because the process of transmission in the field is not well-understood, we are currently conducting a comprehensive assessment of sexual stage parasites in our field site in Mali and determining possible targets of antibodies that might block transmission to mosquitoes. Understanding the assays that are utilized to measure transmission blocking, the parasite antigens that might be effective vaccine candidates against sexual stage parasites, and the process of malaria transmission in the field will aid in efforts to develop a vaccine to block transmission of infection as a novel strategy for control of this disease.

Biography

Dr. Long received her Ph.D. in microbiology and immunology from the University of Pennsylvania and also did postdoctoral 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. 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 immune responses to malaria parasites, particularly in those living in malaria-endemic areas, and also on identification and evaluation of possible candidate antigens for malaria vaccines.

Research Group

Front row: Luwen Zhou, Kazutoyo Miura, Carole Long, Bo Peng, Bingbing Deng
Back row: Greg Tullo, Eugene Oteng, Ababacar Diouf, Sam Moretz, James Alaro
Not pictured: Daria Nikolaeva

Photo of Long Lab members, August 2013

Selected Publications

Miura K, Diakite M, Diouf A, Doumbia S, Konate D, Keita AS, Moretz SE, Tullo G, Zhou H, Lopera-Mesa TM, Anderson JM, Fairhurst RM, Long CA. Relationship between malaria incidence and IgG levels to Plasmodium falciparum merozoite antigens in Malian children: impact of hemoglobins S and C. PLoS One. 2013;8(3):e60182.

Miura K, Herrera R, Diouf A, Zhou H, Mu J, Hu Z, MacDonald NJ, Reiter K, Nguyen V, Shimp RL Jr, Singh K, Narum DL, Long CA, Miller LH. Overcoming allelic specificity by immunization with five allelic forms of Plasmodium falciparum apical membrane antigen 1. Infect Immun. 2013 May;81(5):1491-501.

Miura K, Deng B, Tullo G, Diouf A, Moretz SE, Locke E, Morin M, Fay MP, Long CA. Qualification of standard membrane-feeding assay with Plasmodium falciparum malaria and potential improvements for future assays. PLoS One. 2013;8(3):e57909.

Douglas AD, Williams AR, Illingworth JJ, Kamuyu G, Biswas S, Goodman AL, Wyllie DH, Crosnier C, Miura K, Wright GJ, Long CA, Osier FH, Marsh K, Turner AV, Hill AV, Draper SJ. The blood-stage malaria antigen PfRH5 is susceptible to vaccine-inducible cross-strain neutralizing antibody. Nat Commun. 2011 Dec 20;2:601.

Visit PubMed for a complete publication listing.

Images

Growth inhibition assay (GIA) procedure
In vitro parasite growth inhibition assay (GIA) to assess functional activity of antibodies to merozoite antigens. This assay measures the ability of antibodies to prevent the invasion of merozoites into red cells. Late stage malaria-infected red cells are mixed with antibodies to specific merozoite antigens, and the degree of successful malaria infection and parasites replication is measured 40 hours later by quantitation of parasite lactate dehydrogenase.
Credit: NIAID
 
Human monocytes phagocytosing red cells infected with malaria parasites
Human monocytes phagocytosing red cells infected with malaria parasites. Cell on the left has no parasite, while the three cells on the right have engulfed different numbers of parasites. (L. Lambert et al., manuscript submitted). Credit: NIAID
 
Mosquito membrane feeding assay
Mosquito membrane feeding assay. Mosquitoes are fed on blood containing the cultured sexual stages of malaria parasites. One week later, the mosquito mid-guts are dissected and stained. The red circular oocysts on the right contain infectious stages of the parasites called sporozoites, which migrate to the mosquito salivary glands. Credit: NIAID

Last Updated August 16, 2013