Ad35.CS.01 - RTS,S/AS01 Heterologous Prime Boost Vaccine Efficacy against Sporozoite Challenge in Healthy Malaria-Naïve Adults

• Published in: PloS one Vol. 10; no. 7; p. e0131571
• Main Authors: Ockenhouse, Christian F., Regules, Jason, Tosh, Donna, Cowden, Jessica, Kathcart, April, Cummings, James, Paolino, Kristopher, Moon, James, Komisar, Jack, Kamau, Edwin, Oliver, Thomas, Chhoeu, Austin, Murphy, Jitta, Lyke, Kirsten, Laurens, Matthew, Birkett, Ashley, Lee, Cynthia, Weltzin, Rich, Wille-Reece, Ulrike, Sedegah, Martha, Hendriks, Jenny, Versteege, Isabella, Pau, Maria Grazia, Sadoff, Jerold, Vanloubbeeck, Yannick, Lievens, Marc, Heerwegh, Dirk, Moris, Philippe, Guerra Mendoza, Yolanda, Jongert, Erik, Cohen, Joe, Voss, Gerald, Ballou, W. Ripley, Vekemans, Johan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.07.2015; Public Library of Science (PLoS)
• Subjects: Adenoviruses; Adults; Antibodies, Protozoan - immunology; Antibody Formation - immunology; Antigens; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Clinical trials; Confidence intervals; Double-Blind Method; Drug dosages; Effectiveness; Humans; Immunization; Immunization, Secondary - methods; Immunogenicity; Immunoglobulin G; Immunoglobulin G - immunology; Immunologic Tests - methods; Infections; Interferon; Interferon-gamma - immunology; Lymphocytes; Lymphocytes T; Malaria; Malaria - immunology; Malaria - prevention & control; Malaria Vaccines - immunology; Monkeys & apes; Plasmodium falciparum; Proteins; Sporozoites - immunology; Vaccination - methods; Vaccine efficacy; Vaccines; Vector-borne diseases; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0131571

In an observer blind, phase 2 trial, 55 adults were randomized to receive one dose of Ad35.CS.01 vaccine followed by two doses of RTS,S/AS01 (ARR-group) or three doses of RTS,S/AS01 (RRR-group) at months 0, 1, 2 followed by controlled human malaria infection. ARR and RRR vaccine regimens were well tolerated. Efficacy of ARR and RRR groups after controlled human malaria infection was 44% (95% confidence interval 21%-60%) and 52% (25%-70%), respectively. The RRR-group had greater anti-CS specific IgG titers than did the ARR-group. There were higher numbers of CS-specific CD4 T-cells expressing > 2 cytokine/activation markers and more ex vivo IFN-γ enzyme-linked immunospots in the ARR-group than the RRR-group. Protected subjects had higher CS-specific IgG titers than non-protected subjects (geometric mean titer, 120.8 vs 51.8 EU/ml, respectively; P = .001). An increase in vaccine efficacy of ARR-group over RRR-group was not achieved. Future strategies to improve upon RTS,S-induced protection may need to utilize alternative highly immunogenic prime-boost regimens and/or additional target antigens. ClinicalTrials.gov NCT01366534.