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

PLoS One. 2015 Jul 6;10(7):e0131571. doi: 10.1371/journal.pone.0131571. eCollection 2015.


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.

Trial registration: NCT01366534.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antibodies, Protozoan / immunology
  • Antibody Formation / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Double-Blind Method
  • Humans
  • Immunization, Secondary / methods
  • Immunoglobulin G / immunology
  • Immunologic Tests / methods
  • Interferon-gamma / immunology
  • Malaria / immunology*
  • Malaria / prevention & control*
  • Malaria Vaccines / immunology*
  • Sporozoites / immunology*
  • Vaccination / methods


  • Antibodies, Protozoan
  • Immunoglobulin G
  • Malaria Vaccines
  • Interferon-gamma

Associated data