J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/04/1153/10 $2.00
Volume 185, Number 7, April 7, 1997 1153-1162

Early HIV-1 Envelope-specific Cytotoxic T Lymphocyte Responses in Vertically Infected Infants

By 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.

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