Research Groups
Cellular Immunology
Research Interests and Description
Group Leader: Jeffrey Dorfman, PhD
Group Members
Rajesh Abraham Jacob, PhD Student
René Ghislain Essomba, PhD Student
Fatima Abrahams, Research Technician
Research Interests
The role of antibody responses in protection against human immunodeficiency virus (HIV) and P. falciparum malariaDescription of Research
HIV and Plasmodia induce striking antibody and T cell responses in humans. Nonetheless, much of this response is not protective to the host, and the parameters of this remain poorly understood. More information concerning effective immunity to HIV and P. falciparum will be necessary to design an effective vaccine. We aim to isolate protective human monoclonal antibodies and use them to identify sensitive epitopes/antigens and to assist in the design of more effective vaccine antigens.Neutralisation antibodies for HIV from Clade C-infected donors
- isolation of broadly neutralising anti-HIV antibodies & characterisation of epitopes
Evidence supports neutralising antibody as an important mechanism for protection by a future HIV vaccine. However, there is not enough information about the targeting of neutralising antibodies that are effective against a broad range of HIV isolates (“broadly neutralising antibodies”) to successfully inform vaccine design. To date, most of the research activity isolating neutralising monoclonal antibodies has focused upon antibodies from clade B-infected donors. This is so in spite of the fact that (i) approximately half of HIV infections worldwide are clade C infections including most infections in southern Africa, (ii) the regions of the Envelope protein targeted by antibodies that neutralise clade C isolates are at least partially different than those that neutralise clade B isolates, and (iii) polyclonal antibodies in sera from clade C-infected individuals tend to be more broadly cross-reactive than those from other infected individuals. This project may give us the opportunity not only to rectify this imbalance and contribute to vaccine design but also to bring human monoclonal antibody technology to South Africa and eventually to the service of other developing world public health problems.
P falciparum malaria
- isolation of antibodies useful for better characterisation of the surface of the infected red blood cell (iRBC);
- identification of antibodies with in vitro functional activity associated with protection from disease, and their antigens
Antibodies play an important role in immunity to P. falciparum; however, it is thought that only a small portion of that antibody response is thought to be effective against the parasite. Here, we wish to isolate particular monoclonal antibodies that bin to the relatively poorly characterised surface of the infected red blood cell (iRBC) which expresses proteins that the parasite forces to its surface. We aim to identify the antigens they recognise, and identify which antibodies have activity in in vitro functional assays mimicking protection.
In collaboration with the laboratory of Dr. Patrick Duffy, Seattle, USA, we have two monoclonal antibodies isolated because of their ability to bind to the surface of field parasite lines and undergoing further analysis. One of these is specific for a pregnancy-associated parasite.
Recent Publications
Veiga, J., Feinerman, O., Dorfman, J.R., Germain, R.N., Altan-Bonnet, G. 2008. Phenotypic variability of T cell signaling reveals flexibility in self/non-self discrimination. Science 321, 1081-1084Oleinikov, A.V., Francis, S.E., Dorfman, J.R., Rossnagle, E., Balcaitis, S., Getz, T., Avril, M., Gose, S., Smith, J.D., Fried, M., Duffy, P.E. 2008. VAR2CSA domains expressed in E.coli induce cross-reactive antibodies to native protein. J Infect Dis 197, 1119-1123
Dorfman, J.R., Bejon, P., Ndungu, F.M., Langhorne, J., Kortok, M.M., Lowe, B.S., Mwangi, T.W., Williams, T.N., Marsh, K. 2005. B cell memory to three P. falciparum blood stage antigens in a malaria-endemic area. J Infect Dis 191, 1623-1630
Nyakeriga, A.M., Troye-Blomberg, M., Dorfman, J.R., Alexander, N.D., Bäck, R., Kortok, M., Chemtai, A.K., Marsh, K., Williams, T.N. 2004. Iron deficiency and malaria in children living on the coast of Kenya. J Infect Dis 190, 439-47
Jamieson, A.M., Isnard, P., Dorfman, J.R., Coles, M.C., Raulet, D.H. 2004. Turnover and proliferation of NK cells in steady state and lymphopenic conditions. J Immunol 172, 864-870
Stefanová, I., Dorfman, J.R., Germain, R.N. 2002. Self-recognition promotes the foreign antigen sensitivity of naive T lymphocytes. Nature 420, 429-34
