title: Ad35.CS.01-RTS,S/AS01 Heterologous Prime Boost Vaccine Efficacy against Sporozoite Challenge in Healthy Malaria-Naïve Adults.
abstract: METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01366534.
authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Ockenhouse
authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.
authors.forename: Jason
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authors.lastname: Regules
authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.
authors.forename: Donna
authors.initials: D
authors.lastname: Tosh
authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.
authors.forename: Jessica
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authors.lastname: Cowden
authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.
authors.forename: April
authors.initials: A
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authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.
authors.forename: James
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authors.lastname: Cummings
authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.
authors.forename: Kristopher
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authors.lastname: Paolino
authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.
authors.forename: James
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authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.
authors.forename: Jack
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authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.
authors.forename: Edwin
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authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.
authors.forename: Thomas
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authors.lastname: Oliver
authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.
authors.forename: Austin
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authors.lastname: Chhoeu
authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.
authors.forename: Jitta
authors.initials: J
authors.lastname: Murphy
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, United States of America.
authors.forename: Kirsten
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authors.lastname: Lyke
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, United States of America.
authors.forename: Matthew
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authors.affiliation: PATH-MVI, Washington, DC, United States of America.
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authors.affiliation: PATH-MVI, Washington, DC, United States of America.
authors.forename: Cynthia
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authors.lastname: Lee
authors.affiliation: PATH-MVI, Washington, DC, United States of America.
authors.forename: Rich
authors.initials: R
authors.lastname: Weltzin
authors.affiliation: PATH-MVI, Washington, DC, United States of America.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Wille-Reece
authors.affiliation: Naval Medical Research Center, Silver Spring, MD, United States of America.
authors.forename: Martha
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authors.lastname: Sedegah
authors.affiliation: Crucell Holland BV, Leiden, Netherlands.
authors.forename: Jenny
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authors.lastname: Hendriks
authors.affiliation: Crucell Holland BV, Leiden, Netherlands.
authors.forename: Isabella
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authors.lastname: Versteege
authors.affiliation: Crucell Holland BV, Leiden, Netherlands.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Pau
authors.affiliation: Crucell Holland BV, Leiden, Netherlands.
authors.forename: Jerold
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authors.lastname: Sadoff
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Vanloubbeeck
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Lievens
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Dirk
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authors.lastname: Heerwegh
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moris
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Guerra Mendoza
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: Jongert
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Gerald
authors.initials: G
authors.lastname: Voss
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: W Ripley
authors.initials: WR
authors.lastname: Ballou
authors.affiliation: GSK Vaccines, Rixensart, Belgium.
authors.forename: Johan
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authors.lastname: Vekemans
mesh_terms: D000913:Antibodies, Protozoan / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004311:Double-Blind Method; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D007074:Immunoglobulin G / Q000276:immunology; D007159:Immunologic Tests / Q000379:methods; D007371:Interferon-gamma / Q000276:immunology; D008288:Malaria / Q000276:immunology* / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000276:immunology*; D034101:Sporozoites / Q000276:immunology*; D014611:Vaccination / Q000379:methods
chemical_list: D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D007371:Interferon-gamma