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Article

Cheryl A. Pikora^*, John L. Sullivan^*, Dennis Panicali, and Katherine Luzuriaga^*

From the ^* Department of Pediatrics, Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester, Massachusetts 01605; and Therion Biologics Corporation, Cambridge, Massachusetts 02142

High frequencies of cytotoxic T lymphocyte precursors (CTLp) recognizing HIV-1 laboratory strain gene products have been detected in adults within weeks of primary infection. In contrast, HIV-1–specific CTLp are uncommonly detected in infants younger than 6 mo. To address the hypothesis that the use of target cells expressing laboratory strain env gene products might limit the detection of HIV-1 env-specific CTLp in early infancy, recombinant vaccinia vectors (vv) expressing HIV-1 env genes from early isolates of four vertically infected infants were generated. The frequencies of CTLp recognizing target cells infected with vv-expressing env gene products from early isolates and HIV-1 IIIB were serially measured using limiting dilution followed by in vitro stimulation with mAb to CD3. In one infant, the detection of early isolate env-specific CTLp preceded the detection of IIIB-specific CTLp. CTLp recognizing HIV-1 IIIB and infant isolate env were detected by 6 mo of age in two infants. In a fourth infant, HIV-1 IIIB env and early isolate env-specific CTLp were simultaneously detected at 12 mo of age. These results provide evidence that young infants can generate HIV-1–specific CTL responses and provide support for the concept of neonatal vaccination to prevent HIV-1 transmission. However, the early predominance of type-specific CTL detected in some young infants suggests that the use of vaccines based on laboratory strains of HIV-1 may not protect against vertical infection.

Support for this work was provided by National Institutes of Health (NIH) grants AI-32907, AI-32391, AI26507, and NIH training grant 5T32-AI07349.

¹Abbreviations used in this paper: CM, complete media; CTLp, cytotoxic T lymphocyte precursors; LCMV, lymphocyte choriomeningitis; m.o.i., multiplicity of infection; vv, vaccinia vectors.

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