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Recombinant HIV-1 Glycoprotein 120 Induces Distinct Types of Delayed Hypersensitivity in Persons With or Without Pre-Existing Immunologic Memory¹

Florian Hladik^*,, Sean Bender, Robert E. Akridge, YuXiang Hu, Christine Galloway, Don Francis and M. Juliana McElrath^2,*,,

^* Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; Departments of Medicine and Laboratory Medicine, University of Washington School of Medicine, Seattle, WA 98195; and VaxGen, South San Francisco, CA 94080

Induction of T cell help is critical in HIV-1 control and potentially in prevention by immunization. A practical approach is needed to identify HIV-1-specific helper activities in vivo. We explored the feasibility of measuring delayed-type hypersensitivity (DTH) following intradermal injection of recombinant soluble HIV-1_MN glycoprotein 120 in HIV-1-infected, vaccinated, and exposed individuals. DTH reactions were elicited within 48 h in 16 of 29 untreated, infected patients and in 24 of 30 uninfected vaccinees. Concomitant envelope-specific lymphoproliferation in vitro was undetectable among 9 infected patients tested with positive envelope-specific DTH. By contrast, no 48-h DTH reactions occurred among 25 high risk and 32 low risk, uninfected volunteers. However, 7–12 days after injection, 10 (40%) high risk and 11 (34%) low risk individuals developed induration resembling DTH, and the cellular infiltrates contained monocytes and T cells. Five of 18 examined also developed anti-gp120 Abs. The very delayed time course and lack of correlation with previous Ag exposure clearly distinguish this reaction from DTH. Thus, HIV-1 skin testing can identify persons with HIV-specific recall responses resulting from infection, in the absence of in vitro lymphoproliferation, and from vaccination. In contrast, very late reactivities may signify chemotactic properties of the envelope protein and/or herald the induction of primary HIV-specific Th1-type immunity.