Safety, Immunogenicity, and Efficacy of Plasmodium falciparum Repeatless Circumsporozoite Protein Vaccine Encapsulated in Liposomes

• Published in: The Journal of infectious diseases Vol. 174; no. 2; pp. 361 - 366
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.08.1996; University of Chicago Press; Oxford University Press
• Subjects: Adolescent; Adult; Antibodies; Antigens; Antigens, Protozoan - adverse effects; Antigens, Protozoan - immunology; Antigens, Protozoan - therapeutic use; Biological and medical sciences; Cytotoxicity, Immunologic; Dosage; Dose-Response Relationship, Drug; Drug Carriers; Female; Human protozoal diseases; Humans; Immunization; Infectious diseases; Liposomes; Lymphocyte Activation; Major Articles; Malaria; Malaria Vaccines - adverse effects; Malaria Vaccines - immunology; Malaria Vaccines - therapeutic use; Malaria, Falciparum - prevention & control; Male; Medical sciences; Middle Aged; Parasitic diseases; Plasmodium falciparum; Protozoal diseases; Protozoan Proteins - adverse effects; Protozoan Proteins - immunology; Protozoan Proteins - therapeutic use; Repetitive Sequences, Nucleic Acid; Safety; Sporozoites; T lymphocytes; Vaccination; Vaccines, Synthetic - adverse effects; Vaccines, Synthetic - immunology; Vaccines, Synthetic - therapeutic use; Volunteerism; Human; Protozoa; Protozoal disease; Malaria; Treatment efficiency; Vaccine; Parasitosis; Intramuscular administration; Infection; Immunoprophylaxis; Plasmodium falciparum; Immunogenicity; Sporozoa
• ISSN: 0022-1899; 1537-6613
• 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.