Safety, tolerability, and antibody responses in humans after sequential immunization with a PfCSP DNA vaccine followed by the recombinant protein vaccine RTS,S/AS02A

Vaccine. 2004 Apr 16;22(13-14):1592-603. doi: 10.1016/j.vaccine.2004.01.031.


Optimal protection against malaria may require induction of high levels of protective antibody and CD8(+) and CD4(+) T cell responses. In humans, malaria DNA vaccines elicit CD8(+) cytotoxic T cells (CTL) and IFNgamma responses as measured by short-term (ex vivo) ELISPOT assays, and recombinant proteins elicit antibodies and excellent T cell responses, but no CD8(+) CTL or CD8(+) IFNgamma-producing cells as measured by ex vivo ELISPOT. Priming with DNA and boosting with recombinant pox virus elicits much better T cell responses than DNA alone, but not antibody responses. In an attempt to elicit antibodies and enhanced T cell responses, we administered RTS,S/AS02A, a partially protective Plasmodium falciparum recombinant circumsporozoite protein (CSP) vaccine in adjuvant, to volunteers previously immunized with a P. falciparum CSP DNA vaccine (VCL-2510) and to naïve volunteers. This vaccine regimen was well tolerated and safe. The volunteers who received RTS,S/AS02A alone had, as expected, antibody and CD4(+) T cell responses, but no CD8(+) T cell responses. Volunteers who received PfCSP DNA followed by RTS,S/AS02A had antibody and CD8(+) and CD4(+) T cell responses (Wang et al., submitted). Sequential immunization with DNA and recombinant protein, also called heterologous prime-boost, led to enhanced immune responses as compared to DNA or recombinant protein alone, suggesting that it might provide enhanced protective immunity.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antibodies, Protozoan / analysis
  • Antibodies, Protozoan / biosynthesis*
  • B-Lymphocytes / immunology
  • Female
  • Hepatitis B Antibodies / biosynthesis
  • Hepatitis B Surface Antigens / immunology
  • Humans
  • Immunization Schedule
  • Malaria Vaccines / adverse effects
  • Malaria Vaccines / immunology*
  • Male
  • Plasmodium falciparum / immunology*
  • Spores, Protozoan / immunology
  • T-Lymphocytes / immunology
  • Vaccines, DNA / adverse effects
  • Vaccines, DNA / immunology*
  • Vaccines, Synthetic / adverse effects
  • Vaccines, Synthetic / immunology


  • Antibodies, Protozoan
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Malaria Vaccines
  • PfCSP DNA vaccine
  • Vaccines, DNA
  • Vaccines, Synthetic