PLoS ONE (Jan 2015)

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

  • Christian F Ockenhouse,
  • Jason Regules,
  • Donna Tosh,
  • Jessica Cowden,
  • April Kathcart,
  • James Cummings,
  • Kristopher Paolino,
  • James Moon,
  • Jack Komisar,
  • Edwin Kamau,
  • Thomas Oliver,
  • Austin Chhoeu,
  • Jitta Murphy,
  • Kirsten Lyke,
  • Matthew Laurens,
  • Ashley Birkett,
  • Cynthia Lee,
  • Rich Weltzin,
  • Ulrike Wille-Reece,
  • Martha Sedegah,
  • Jenny Hendriks,
  • Isabella Versteege,
  • Maria Grazia Pau,
  • Jerold Sadoff,
  • Yannick Vanloubbeeck,
  • Marc Lievens,
  • Dirk Heerwegh,
  • Philippe Moris,
  • Yolanda Guerra Mendoza,
  • Erik Jongert,
  • Joe Cohen,
  • Gerald Voss,
  • W Ripley Ballou,
  • Johan Vekemans

DOI
https://doi.org/10.1371/journal.pone.0131571
Journal volume & issue
Vol. 10, no. 7
p. e0131571

Abstract

Read online

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.