Chitraporn Karnasuta, Wannee Kantakamalakul, Chaisuree Suphavilai3 and Mark S.
de Souza Department of Retrovirology, USAMC-AFRIMS, Bangkok; Department of Virology,
Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok; and Research Institute for
Health Sciences,Chiangmai University, Chiangmai, Thailand.
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Millions of people worldwide are currently infected with
HIV-1. Despite recent advances in antiretroviral therapy, HIV-1 infections
are still on the rise particularly in less developed countries. In response
to this epidemic, preventive HIV vaccines have been developed and several
HIV vaccine trials have been implemented. Amongst HIV subtype E vaccine
candidates, canarypox HIV (ALVAC-HIV) vaccine candidate - vCP1521,
expressing the products of gp120 envelope gene derived from HIV-1 subtype E
(TH023) and the gag and pol genes of HIV-1 subtype B (HIV-LAI) was
immunologically evaluated in volunteers in Thailand. Prior to the evaluation of
safety and immunogenicity of the vaccine in a phase I/II double-blinded study,
acute safety and tolerability of some components in the vaccine were evaluated.
Fifteen low-risk HIV seronegative Thai adults, comprising of 9 males and
6 females aged between 20 - 45 years, were intramuscularly administered
with either vCP1521 at 106.53 CCID50 (N=10) or oligomeric gp160 TH023/LAI-DID
at 50mg (N=5) at weeks 0, 4, 12 and 24. Cytotoxic T-lymphocyte (CTL) assays
were performed on the peripheral blood mononuclear cells (PBMCs) collected
from the volunteers at weeks 0, 6, 14 and 26 (visits 1, 3, 5 and 7 respectively).
Effectors used in the CTL assay were prepared from PBMCs after a two-week
in vitro stimulation period using vaccinia constructs expressing HIV subtype
E envelope (vP1536) and B gag/pol (vVK1). Targets were prepared from autologous
EBV-transformed B lymphocytes infected with either vP1536 or vVK1. Radioactive
chromium release was used to determine CTL activity. Four out of ten volunteers
demonstrated CTL activity following immunisation with ALVAC-HIV at various
visits and none of the five volunteers responded following immunisation
of oligomeric gp160. CTL assays using positive effectors depleted of CD4+
and CD8+ cells were also conducted on the CTL-positive responders. The results
confirmed that the CTL assay was specific to the CD8+ cell population. Apart
from the acute safety and tolerability shown with the vaccines, ALVAC-HIV
was capable of inducing CTL specific activity in a proportion of these subjects
similar to that seen in other canarypox HIV vaccine trials.
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