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Journal of Virology, November 2000, p. 10514-10522, Vol. 74, No. 22
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.
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
*
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.
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