QS-21 synergizes with recombinant interleukin-12 to create a potent adjuvant formulation for the fusion protein of respiratory syncytial virus.
In the murine model of respiratory syncytial virus (RSV) infection, recombinant interleukin-12 (rIL-12) was previously demonstrated to be most effective as an adjuvant for fusion (F) protein-based vaccines after adsorption to alum adjuvant. Alum, however, is a potent inducer of polarized T-cell responses and the type 2 phenotype. In addition, studies in human cancer patients demonstrated that rIL-12 was toxic when administered systemically at high doses. Because of these issues, we investigated whether the saponin QS-21 could facilitate a reduction in dose of rIL-12 when F protein was prepared in the absence of alum (F/rIL-12). The results demonstrated that a suboptimal dose (0.8 microg) of QS-21 enhanced the capacity of F/rIL-2 to elicit antigen-dependent killer cell precursors and complement-assisted neutralizing antibodies in spleens and sera respectively of BALB/c mice. The killer cell activity of mice vaccinated with F/rIL-12 (0.1 microg) plus 0.8 microg QS-21 was equivalent to that elicited after vaccination by experimental infection, or with an optimal dose of QS-21. The neutralizing titers generated by F/rIL-12 (0.01 to 1.0 microg) were also significantly elevated in the presence of 0.8 microg QS-21. Thus, rIL-12 and QS-21 together form a potent adjuvant for eliciting functional cell-mediated and humoral immune responses against F protein.
Hancock
G E
GE
Department of Immunology Research, Wyeth-Lederle Vaccines, West Henrietta, New York 14586-9728, USA. Hancocg@war.wyeth.com
Heers
K M
KM
Smith
J D
JD
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D004357:Drug Synergism; D006801:Humans; D007117:Immunization, Secondary; D018664:Interleukin-12 / Q000008:administration & dosage / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D012503:Saponins / Q000008:administration & dosage / Q000276:immunology*; D014611:Vaccination; D014764:Viral Proteins / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D011994:Recombinant Proteins; D022261:Respiratory Syncytial Virus Vaccines; D012503:Saponins; D014764:Viral Proteins; D018664:Interleukin-12; C078785:saponin QA-21V1; D003165:Complement System Proteins