Carole Long, Ph.D.

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 initiated a new project in 2013 for a comprehensive assessment of dynamics of erythrocyte and sexual stage parasites and immunity and sexual stage parasites in our field site in Mali, and we are currently 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.

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

P. falciparum gametocyte prevalence detected by Pfs25-based RT-PCR in Kenieroba, Mali, from June 2013 to May 2014. Five hundred people in all age ranges were followed for their total parasite and gametocyte positivity for one year. N.D.; not determined yet

Credit: NIAID

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. (Lambert L et al., manuscript submitted).

Credit: NIAID