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The Journal of Immunology, 1971, 106: 1191-1200.
Copyright © 1971 by The American Association of Immunologists, Inc.
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Regulation of the Immune System by Synthetic Polynucleotides

I. Characteristics of Adjuvant Action on Antibody Synthesis1

Jon R. Schmidtke2 and Arthur G. Johnson

From the Department of Microbiology, The University of Michigan, Ann Arbor, Michigan 48104

Abstract

Equimolar complexes of the synthetic polyribonucleotides, polyadenylic and polyuridylic acid (poly(A:U)), or polyinosinic and polycytidylic acid (poly(I:C)) were shown to be adjuvants for antibody formation in mice. A decreased induction period and increases in 19S and 7S antibody titers and in immunologic memory were noted. Poly(A:U) increased the antibody response to a variety of antigens including both soluble and particulate proteins, sheep red blood cells, and a polysaccharide, the Vi antigen of Escherichia coli. In addition, antibody formation to bovine {gamma} globulin was enhanced in mice, rabbits and guinea pigs. Antigenicity was increased considerably in that poly(A:U) was capable of rendering 1 ng of bovine {gamma} globulin immunogenic. When injected 0.5 to 1 day before antigen, poly(A:U) was found to be immunosuppressive. However, a second injection of poly(A:U) given with antigen abolished the immunosuppression induced by the first dose of poly(A:U). Study of various physical and chemical factors necessary for the adjuvant action of poly(A:U) revealed that no polynucleotide alone acted as an adjuvant nor were other known interferon-inducing polymers effective. Complexes composed of altered molar proportions were no more effective than an equimolar complex, and neither purine nor pyrimidine mono- and oligonucleotides could replace their respective polynucleotides in the poly(A:U) complex. Decreasing the hydrogen bonding in the complex through use of chemically modified poly A and poly U caused a reduction in the adjuvant action. In addition, neither repeated freeze-thawing nor prolonged incubation at room temperature minimized the adjuvant action of poly (A:U). Heat denaturation rendered the complex ineffective, as did treatment with ribonuclease or incubation in normal mouse serum.

Footnotes

1 This work was supported by United States Public Health Service Grants AI-1524 and AM-14273. Presented in part at the 68th and 69th Annual Meetings of the Society for Microbiology, Detroit, Michigan, May 1968, and Miami Beach, Florida, May 1969, respectively; and at the 53rd and 54th Annual Meetings of the American Association of Immunologists, Atlantic City, New Jersey, April 1969 and April 1970, respectively.

2 United States Public Health Service Predoctoral Fellow, No. 1 FI-GM 37,826. Present Address: Department of Experimental Pathology, Scripps Clinic and Research Foundation, La Jolla, California 92037.




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W. A. Carter and E. De Clercq
Viral Infection and Host Defense
Science, December 27, 1974; 186(4170): 1172 - 1178.
[Abstract] [PDF]


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