Efficacy of Recombinant Circumsporozoite Protein Vaccine Regimens against Experimental Plasmodium falciparum Malaria

• Published in: The Journal of infectious diseases Vol. 183; no. 4; pp. 640 - 647
• Main Authors: Kester, Kent E., McKinney, Denise A., Tornieporth, Nadia, Ockenhouse, Christian F., Heppner, D. Gray, Hall, Ted, Krzych, Urszula, Delchambre, Martine, Voss, Gerald, Dowler, Megan G., Palensky, Jolie, Wittes, Janet, Cohen, Joe, Ballou, W. Ripley
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.02.2001; University of Chicago Press; Oxford University Press
• Subjects: Adolescent; Adult; Animals; Antibodies; Antibodies, Protozoan - blood; Antigens; Biological and medical sciences; circumsporozoites; Dosage; Female; Fundamental and applied biological sciences. Psychology; Geometric mean; Hepatitis antigens; Hepatitis B vaccines; Human protozoal diseases; Humans; Infectious diseases; Lymphocyte Activation; Major Articles; Malaria; Malaria vaccine; Malaria Vaccines - administration & dosage; Malaria Vaccines - adverse effects; Malaria Vaccines - immunology; Malaria, Falciparum - prevention & control; Male; Medical sciences; Microbiology; Middle Aged; Parasitic diseases; Plasmodium falciparum; Plasmodium falciparum - immunology; Protozoal diseases; Protozoan Proteins - genetics; Protozoan Proteins - immunology; Recombinant Proteins - immunology; Sporozoites; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - immunology; Virology; Protozoa; Apicomplexa; Protozoal disease; Immunization; Malaria; Vision disorder; Vaccine; Parasitosis; Standards; Infection; Plasmodium falciparum; Eye disease; Treatment; Immunogenicity; Blindness; Recombinant protein
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/318534

After initial successful evaluation of the circumsporozoite-based vaccine RTS,S/SBAS2, developed by SmithKline Beecham Biologicals with the Walter Reed Army Institute of Research, protective efficacy of several regimens against Plasmodium falciparum challenge was determined. A controlled phase 1/2a study evaluated 1 or 2 standard doses of RTS,S/SBAS2 in 2 groups whose members received open-label therapy and 3 immunizations in blinded groups who received standard, one-half, or one-fifth doses. RTS,S/SBAS2 was safe and immunogenic in all groups. Of the 41 vaccinees and 23 control subjects who underwent sporozoite challenge, malaria developed in 7 of 10 who received 1 dose, in 7 of 14 who received 2 doses, in 3 of 6 who received 3 standard doses, in 3 of 7 who received 3 one-half doses, in 3 of 4 who received 3 one-fifth doses, and in 22 of 23 control subjects. Overall protective efficacy of RTS,S/SBAS2 was 41% (95% confidence interval, 22%–56%; P = .0006). This and previous studies have shown that 2 or 3 doses of RTS,S/SBAS2 protect against challenge with P. falciparum sporozoites.