Heppner D G, Gordon D M, Gross M, Wellde B, Leitner W, Krzych U, Schneider I, Wirtz R A, Richards R L, Trofa A, Hall T, Sadoff J C, Boerger P, Alving C R, Sylvester D R, Porter T G, Ballou W R
Department of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC, USA.
J Infect Dis. 1996 Aug;174(2):361-6. doi: 10.1093/infdis/174.2.361.
Seventeen malaria-naive volunteers received a recombinant Plasmodium falciparum vaccine (RLF) containing the carboxy- and the amino-terminal of the circumsporozoite protein (CSP) antigen without the central tetrapeptide repeats. The vaccine was formulated in liposomes with either a low or high dose of 3-deacylated monophosphoryl lipid A (MPL) and administered with alum by intramuscular injection. Both formulations were well tolerated and immunogenic. MPL increased sporozoite antibody titers measured by ELISA, Western blot, and immunofluorescence assay. One high-dose MPL vaccine formulation recipient developed a CSP-specific cytotoxic T lymphocyte response. After homologous sporozoite challenge, immunized volunteers developed patent malaria. There was no correlation between prepatent period and antibody titers to the amino- or carboxy-terminal. The absence of delay in patency argues against inclusion of the amino-terminal in future vaccines. A significant cytotoxic T lymphocyte response may have been suppressed by the inclusion of alum as an adjuvant.
