In:
Journal of Virology, American Society for Microbiology, Vol. 77, No. 24 ( 2003-12-15), p. 13348-13360
Abstract:
Given
the current difficulties generating vaccine-induced neutralizing antibodies to human immunodeficiency virus (HIV), the focus of the
vaccine community has shifted toward creating cytotoxic-T-lymphocyte (CTL)-based vaccines. Recent reports of CTL-based vaccine trials in
macaques challenged with simian/human immunodeficiency virus SHIV-89.6P have supported the notion that such vaccines can
ameliorate the course of disease. However, almost all of these studies included Env as an immunogen and since SHIV-89.6P is sensitive to
neutralizing antibodies it is difficult to determine the mechanism(s) of protection. Consequently, SHIV-89.6P challenge of macaques may be a
poor model for determining vaccine efficacy in humans. To ascertain the effect of vaccine-induced multispecific mucosal CTL, in the absence of
Env-specific antibody, on the control of an immunodeficiency virus challenge, we vaccinated Mamu-A*01 + macaques with
constructs encoding a combination of CTL epitopes and full-length proteins (Tat, Rev, and Nef) by using a DNA prime/recombinant modified
vaccinia virus Ankara (rMVA) boost regimen. The vaccination induced virus-specific CTL and CD4 + helper T lymphocytes
with CTL frequencies as high as 20,000/million peripheral blood mononuclear cells. The final rMVA vaccination, delivered intravenously,
engendered long-lived mucosal CTL. At 16 weeks after the final rMVA vaccination, the vaccinees and naive, Mamu-A*01 + controls were challenged intrarectally with
SIVmac239. Massive early anamnestic cellular immune responses controlled acute-phase viral replication; however, the three
vaccinees were unable to control virus replication in the chronic phase. The present study suggests that multispecific mucosal CTL, in
the absence of neutralizing antibodies, can achieve a modicum of control over early viral replication but are unable to control
chronic-phase viral replication after a high-dose mucosal challenge with a pathogenic simian immunodeficiency
virus.
Type of Medium:
Online Resource
ISSN:
0022-538X
,
1098-5514
DOI:
10.1128/JVI.77.24.13348-13360.2003
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2003
detail.hit.zdb_id:
1495529-5
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