ADJUVANTICITY OF STEARYL-TYROSINE--SUBUNIT & HIV SYSTEM

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Stearyl-tyrosine (ST) is a naturally occuriring saturated fatty alcohol esterified with a naturally occurring amino acid. It has the capacity to adsorb antigen and release it slowly. Preliminary studies have shown that ST like alum can enhance immune responses. Usage of ST as an adjuvant may represent an advantage since, it lacks the side effects observed in the case of Alum, long chain ethyl amine substances and other adjuvants. During the past two years evidence has been provided that stearyl-tyrosine is a stable and safe synthetic compound exhibiting a stronger adjuvant activity than Alum ith respect to the enhancement of antibody response elicited by tetanus toxoid, poliovirus vaccine, hepatitis B surface antigen and two synthetic peptides derived from the HIV gpl2O protein. Various toxicity tests showed that this compound is - safe. The major goal of this project is to evaluate the adjuvant activity of stearyl-tyrosine which appears to be acceptable for human use. The specific aims of our proposal are as follows: 1. To study the enhancement of antibody response against various antigens by ST. These studies will include antigens representing a protatype for the development of new generation of vaccines which tend to be poor immunagens such as subunit vaccines. synthetic peptides and idiotype vaccines. 2. To study the effect of ST adjuvant on the antibody response in monkeys immunized with synthetic peptides corresponding to four epitopes borne by gp160 envelope protein of HIV virus. 3.To study the effect of ST on cell mediated immune response elicited by HIV gpl2O protein or synthetic peptides. 4. To study the side effects of ST with respect to immunogenicity and the activation of autoreactive clones. 5. To develop new naturally occurring fatty alcohol derivatives of amino acids with the goal of establishing a new derivative having stronger adjuvanticity and devoid of side effects. The ultimate goal of this project is to develop an adjuvant which is suitable for human use in the vaccination against HIV.rr