TY - JOUR
T1 - Resistance to human immunodeficiency virus type 1 in vitro as a surrogate of vaccine-induced protective immunity
AU - Castillo, Renan C.
AU - Arango-Jaramillo, Silvio
AU - John, Rohan
AU - Weinhold, Kent
AU - Kanki, Phyllis
AU - Carruth, Lucy Minnich
AU - Schwartz, David H.
N1 - Funding Information:
Received 19 April 1999; revised 1 November 1999; electronicallypublished 20 March 2000. Presented in part: 5th Conference on Retroviruses and Opportunistic Infections, Chicago, February 1998 (session 16; paper 91). Informed consent was obtained from all subjects participating in this study. This study conformed to human experimentation guidelines of the US Department of Health and Human Services and was approved by the Johns Hopkins University Institutional Review Board. Financial support: NIH (grant AI-40898; contract AI-45207). a These authors contributed equally to the work. Reprints or correspondence: Dr. David H. Schwartz, Dept. of Molecular Microbiology and Immunology, School of Hygiene and Public Health, Johns Hopkins University, 615 N. Wolfe St., Baltimore, MD 21205 (dschwart@jhsph.edu).
PY - 2000
Y1 - 2000
N2 - An in vitro assay developed as a correlate of vaccine-induced protection from human immunodeficiency virus (HIV) was validated in populations with relative resistance to HIV-1 as well as in HIV vaccine recipients. Cultures of peripheral blood mononuclear cells (PBMC) were challenged with 10 TCID50 of HIV-1(MN) or HIV-1(BaL), titered in PBMC from normal controls (n = 57). PBMC from HIV-1-infected persons with low viremia (n = 17), exposed uninfected persons (n = 23), and HIV-2-infected Senegalese prostitutes (n = 9) were significantly resistant to HIV-1(BaL) and/or HIV-1(MN) (P < .001). Among 34 HIV vaccine recipients of live canarypox vector expressing multiple HIV-1 gene products with or without rgp120 booster, PBMC from postvaccination samples were significantly resistant to both strains (P < .001), and cytotoxic T lymphocyte precursor-positive samples were significantly more resistant than were precursor-negative samples (P < .03). This is the first evidence of the induction by vaccination of a validated correlate of protection. This assay should serve as a useful criterion for assessing experimental HIV vaccines before phase III efficacy trials.
AB - An in vitro assay developed as a correlate of vaccine-induced protection from human immunodeficiency virus (HIV) was validated in populations with relative resistance to HIV-1 as well as in HIV vaccine recipients. Cultures of peripheral blood mononuclear cells (PBMC) were challenged with 10 TCID50 of HIV-1(MN) or HIV-1(BaL), titered in PBMC from normal controls (n = 57). PBMC from HIV-1-infected persons with low viremia (n = 17), exposed uninfected persons (n = 23), and HIV-2-infected Senegalese prostitutes (n = 9) were significantly resistant to HIV-1(BaL) and/or HIV-1(MN) (P < .001). Among 34 HIV vaccine recipients of live canarypox vector expressing multiple HIV-1 gene products with or without rgp120 booster, PBMC from postvaccination samples were significantly resistant to both strains (P < .001), and cytotoxic T lymphocyte precursor-positive samples were significantly more resistant than were precursor-negative samples (P < .03). This is the first evidence of the induction by vaccination of a validated correlate of protection. This assay should serve as a useful criterion for assessing experimental HIV vaccines before phase III efficacy trials.
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U2 - 10.1086/315300
DO - 10.1086/315300
M3 - Article
C2 - 10720510
AN - SCOPUS:0034073361
SN - 0022-1899
VL - 181
SP - 897
EP - 903
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 3
ER -