Title: Functional Analysis of Human Monoclonal Antibodies against MSP2

PhD Student: Balam Saidou

Supervisors: Prof. François Spertini (Hospices-CHUV, Switzerland) and Prof. Klavs Berzins (Stockholm University, Sweden)

Collaborators: Prof.Giampietro Corradin (Biochemistry Dept, Lausanne University, Switzerland), Dr. Michael Theisen (Statens Serum Institut, Denmark), Prof. Alan Thomas (BioMedical Primate Research Center, the Netherlands) and Prof. Antonio Lanzavecchia (Institute for Research in Biomedicine, Switzerland)

Background: The laboratories of Drs. Corradin and Spertini in Lausanne and associates are currently evaluating two long synthetic peptides based on the conserved regions of the two allelic families of MSP2 as malaria vaccine candidate. These two allelic families of MSP2 have been associated with protection against malaria infection.

Human purified antibodies specific for both MSP2 candidate vaccines were active in antibody-dependent cellular activity (ADCI) and but not in the growth inhibition assay (GIA).

Aim of the project: We are collaborating with the laboratory of Dr. Lanzavecchia, who has recently optimized the development of human monoclonal antibodies by immortalizing memory B cells (Barford et al 2007) and Lagos State University Teaching Hospital, Nigeria, to develop human monoclonal antibodies against the two allelic families of MSP2.

We plan to evaluate the biological activity of specific IgG subtypes of human monoclonal antibodies and sera from immunized naive volunteers in IFAT, ADCI and GIA. The possible therapeutic effects of the monoclonal antibodies in primate models of P. falciparum will also be planned.

We envisage close interactions with the laboratories of Drs. M. Theisen , K. Berzin and A. Thomas for some of these activities.

Methods: EBV infection, cloning and production of human B cells from donors withhigh antibody titers against the antigens of interest; immunofluorescence; SDS-PAGE electrophoresis; western blot; biological activity using growth inhibition assay (GIA) and antibody dependent cellular inhibition (ADCI); animal handling.

Expected outcome: Production of human monoclonal antibodies specific for the two MSP2 allelic proteins with ADCI biological activity. Mapping of the relevant epitopes.