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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)-gamma-secreting CD4+ T cells. RTS,S-specific IFN-gamma-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-gamma 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 publication

DOI

10.1086/315074

Type

Journal article

Journal

J Infect Dis

Publication Date

11/1999

Volume

180

Pages

1656 - 1664

Keywords

Adult, Amino Acid Sequence, Animals, Antibodies, Protozoan, CD4-Positive T-Lymphocytes, Epitopes, Hepatitis B Surface Antigens, Humans, Interferon-gamma, Lymphocyte Activation, Malaria Vaccines, Malaria, Falciparum, Middle Aged, Molecular Sequence Data, Peptides, Plasmodium falciparum, Protozoan Proteins, T-Lymphocytes, Regulatory, Th1 Cells, Vaccination, Vaccines, Synthetic