Potent induction of focused Th1-type cellular and humoral immune responses by RTS,S/SBAS2, a recombinant Plasmodium falciparum malaria vaccine

Ajit Lalvani, Phillipe Moris, Gerald Voss, Ansar A. Pathan, Kent E. Kester, Roger Brookes, Edwin Lee, Marguerite Koutsoukos, Magdalena Plebanski, Martine Delchambre, Katie L. Flanagan, Cecile Carton, Moncef Slaoui, Christian Van Hoecke, W. Ripley Ballou, Adrian V S Hill, Joe Cohen

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146 Citations (Scopus)

Abstract

The RTS,S/SBAS2 vaccine confers sterile protection against Plasmodium falciparum sporozoite challenge. The mechanisms underlying this are of great interest, yet little is known about the immune effector mechanisms induced by this vaccine. The immune responses induced by RTS,S/SBAS2 were characterized in 10 malaria-naive volunteers. Several epitopes in the circumsporozoite protein (CSP) were identified as targets of cultured interferon (IFN)-γ- secreting CD4+ T cells. RTS,S-specific IFN-γ-secreting effector T cells were induced in 8 subjects; this ex vivo response mapped to a single peptide in Th2R. CSP-specific CD8+ cytotoxic T lymphocytes were not detected. RTS,S- specific IFN-γ production was universal, whereas interleukin-4 and -5 production was rare. RTS,S-specific lymphoproliferative responses and antibodies to CSP were strongly induced in all volunteers. Responses waned with time but were boostable. Thus, RTS,S/SBAS2 is a potent inducer of Th1- type cellular and humoral immunity. These results highlight possible immune mechanisms of protection and have important implications for vaccine design in general.

Original languageEnglish
Pages (from-to)1656-1664
Number of pages9
JournalJournal of Infectious Diseases
Volume180
Issue number5
DOIs
Publication statusPublished - 1999
Externally publishedYes

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