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Journal of Virology, November 2000, p. 10514-10522, Vol. 74, No. 22
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Effective Induction of Simian Immunodeficiency Virus-Specific Systemic and Mucosal Immune Responses in Primates by Vaccination with Proviral DNA Producing Intact but Noninfectious Virions

Shainn-Wei Wang,1 Pamela A. Kozlowski,1 Gretchen Schmelz,1 Kelledy Manson,2 Michael S. Wyand,2 Rhona Glickman,3 David Montefiori,4 Jeffrey D. Lifson,5 R. Paul Johnson,3,6 Marian R. Neutra,1 and Anna Aldovini1,*

Department of Medicine, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts1; Primedica, Worcester, Massachusetts2; Duke University, Durham, North Carolina4; Retroviral Pathogenesis Laboratory, AIDS Vaccine Program, SAIC Frederick, NCI-FCRDC, Frederick, Maryland5; New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts3; and Partners AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Charlestown, Massachusetts6

Received 28 April 2000/Accepted 15 August 2000

We report a pilot evaluation of a DNA vaccine producing genetically inactivated simian immunodeficiency virus (SIV) particles in primates, with a focus on eliciting mucosal immunity. Our results demonstrate that DNA vaccines can be used to stimulate strong virus-specific mucosal immune responses in primates. The levels of immunoglobulin A (IgA) detected in rectal secretions of macaques that received the DNA vaccine intradermally and at the rectal mucosa were the most striking of all measured immune responses and were higher than usually achieved through natural infection. However, cytotoxic T lymphocyte responses were generally low and sporadically present in different animals. Upon rectal challenge with cloned SIVmac239, resistance to infection was observed, but some animals with high SIV-specific IgA levels in rectal secretions became infected. Our results suggest that high levels of IgA alone are not sufficient to prevent the establishment of chronic infection, although mucosal IgA responses may have a role in reducing the infectivity of the initial viral inoculum.

* Corresponding author. Mailing address: Children's Hospital, Enders 609, 300 Longwood Ave., Boston, MA 02115. Phone: (617) 355-8426. Fax: (617) 355-8387. E-mail: anna.aldovini{at}tch.harvard.edu.

Journal of Virology, November 2000, p. 10514-10522, Vol. 74, No. 22
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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