Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Control of Viremia and Prevention of Clinical AIDS in Rhesus Monkeys by Cytokine-Augmented DNA Vaccination
Dan H. Barouch,1*Sampa Santra,1Jörn E. Schmitz,1Marcelo J. Kuroda,1Tong-Ming Fu,2Wendeline Wagner,3Miroslawa Bilska,4Abie Craiu,1Xin Xiao Zheng,1Georgia R. Krivulka,1Kristin Beaudry,1Michelle A. Lifton,1Christine E. Nickerson,1Wendy L. Trigona,2Kara Punt,2Dan C. Freed,2Liming Guan,2Sheri Dubey,2Danilo Casimiro,2Adam Simon,2Mary-Ellen Davies,2Michael Chastain,2Terry B. Strom,1Rebecca S. Gelman,5David C. Montefiori,4Mark G. Lewis,3Emilio A. Emini,2John W. Shiver,2Norman L. Letvin1
With accumulating evidence indicating the importance of
cytotoxic T lymphocytes (CTLs) in containing human immunodeficiencyvirus-1 (HIV-1) replication in infected individuals, strategiesare
being pursued to elicit virus-specific CTLs with prototypeHIV-1
vaccines. Here, we report the protective efficacy of vaccine-elicitedimmune responses against a pathogenic SHIV-89.6P challenge inrhesus
monkeys. Immune responses were elicited by DNA vaccinesexpressing
SIVmac239 Gag and HIV-1 89.6P Env, augmented by theadministration of
the purified fusion protein IL-2/Ig, consistingof interleukin-2 (IL-2)
and the Fc portion of immunoglobulin G(IgG), or a plasmid encoding
IL-2/Ig. After SHIV-89.6P infection,sham-vaccinated monkeys developed
weak CTL responses, rapid lossof CD4+ T cells, no
virus-specific CD4+ T cell responses, high setpoint viral
loads, significant clinicaldisease progression, and death in half of
the animals by day 140after challenge. In contrast, all monkeys that
received the DNAvaccines augmented with IL-2/Ig were infected, but
demonstratedpotent secondary CTL responses, stable CD4+ T
cell counts, preserved virus-specific CD4+ T cell
responses, low to undetectable setpoint viral loads, andno evidence of
clinical disease or mortality by day 140 afterchallenge.
1 Department of Medicine, Beth Israel Deaconess
Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston,
MA 02215, USA.
2 Merck Research Laboratories, West
Point, PA 19486, USA.
3 Southern Research Institute,
431 Aviation Way, Frederick, MD 21701, USA.
4 Duke
University Medical Center, Durham, NC 27710, USA.
5 Department of Biostatistical Science, Dana-Farber
Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
*
To whom correspondence should be addressed. E-mail:
dan_barouch{at}hotmail.com
The editors suggest the following Related Resources on Science sites:
In Science Magazine
LETTERS
Miles B. Markus, John E. Fincham;, Dan H. Barouch, and Norman L. Letvin (5 January 2001) Science291 (5501), 46.
[DOI: 10.1126/science.10.1126/SCIENCE.291.5501.46] |Full Text »
PERSPECTIVES
Xuefei Shen and Robert F. Siliciano (20 October 2000) Science290 (5491), 463.
[DOI: 10.1126/science.290.5491.463] |Summary »|Full Text »
