The immunomodulating properties of human respiratory syncytial virus and immunostimulating complexes containing Quillaja saponin components QH-A, QH-C and ISCOPREP703.
A successful vaccine against human RSV (HRSV) is likely to induce a Th1 or a balanced Th1/TH2 cytokine response. We tested a panel of HRSV immunostimulating complexes (ISCOMs) containing different Quillaja saponin fractions (QH-A, QH-C, and 703: a mixture of 70% QH-A and 30% QH-C) with different immunological properties for their capacity of inducing innate and acquired immune responses. The HRSV 703 ISCOMs induced the strongest innate and acquired immune responses, followed by RSV QH-C and QH-A ISCOMs. All three formulations induced various degrees of Th1 bias response with prominent production of IFN-gamma being 10-50 times higher than that of IL-4 and IL-5. The HRSV specific IgG isotype profile correlated with the predominant secretion of Th1 cytokines, with strong induction of IgG2a antibodies. The 703 ISCOMs induced the most pronounced Th1 profile followed by QH-C and QH-A ISCOMs. The high incorporation of F protein in these ISCOMs compared to G protein combined with the Th1 biased nature of ISCOM are likely to be the causes to promote a Th1 type of profile. The prospect to formulate an RSV ISCOM formulation with an optimal Th1/Th2 balance is in reach particularly in view of the versatile properties of the ISCOM concept.
Hu
Ke-Fei
KF
Section of Virology, Department of Veterinary Microbiology, College of Veterinary Medicine, Swedish University of Agricultural Sciences, Biomedical Center, Box 585, S-751 23 Uppsala, Sweden. kefeihu@yahoo.com
Regner
Matthias
M
Siegrist
Claire-Anne
CA
Lambert
Paul
P
Chen
Margaret
M
Bengtsson
Karin Lövgren
KL
Morein
Bror
B
D000276:Adjuvants, Immunologic; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D016882:ISCOMs / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D051379:Mice; D031990:Quillaja / Q000737:chemistry* / Q000276:immunology*; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D014764:Viral Proteins / Q000276:immunology
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D016882:ISCOMs; D007074:Immunoglobulin G; D015848:Interleukin-5; D022261:Respiratory Syncytial Virus Vaccines; D014764:Viral Proteins; D015847:Interleukin-4; D007371:Interferon-gamma