Potent induction of focused Th1-type cellular and humoral immune responses by RTS,S/SBAS2, a recombinant Plasmodium falciparum malaria vaccine
| Autor: | A. V. S. Hill, Gerald Voss, Katie L. Flanagan, C. Carton, Magdalena Plebanski, Joe Cohen, M. Koutsoukos, Ansar A. Pathan, Ajit Lalvani, Moncef M. GlaxoSmithKline Slaoui, Philippe Moris, Martine Delchambre, Roger H. Brookes, Kent E. Kester, Edwin A. M. Lee, C. Van Hoecke, William Ripley Ballou |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Molecular Sequence Data Plasmodium falciparum Protozoan Proteins Antibodies Protozoan Lymphocyte Activation T-Lymphocytes Regulatory behavioral disciplines and activities Epitopes Interferon-gamma Immune system Antigen Malaria Vaccines parasitic diseases Immunology and Allergy Cytotoxic T cell Animals Humans Amino Acid Sequence Malaria Falciparum Vaccines Synthetic Hepatitis B Surface Antigens biology Malaria vaccine Vaccination RTS S Middle Aged Th1 Cells Virology Circumsporozoite protein Infectious Diseases Humoral immunity Immunology biology.protein Antibody Peptides |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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