final program.qxd - Parallels Plesk Panel

FP 3.1
An HIV-1 peptide-based vaccine inducing cross-subtype immunity in macaques
F.Diaz-Mitoma 1,2 , D.E. Anderson 1 , A.Azizi1, 2 , M.Ghorbani 1,2 , C.Soare 1,2 , A.Ogrel 1 ,
S.Aucoin 1,2 , R.Frost 1,2 , S.Ogrel 1 , and J.V.Torres 1
1
Variation Biotechnologies, Inc., 22 de Varennes, Suite 210, Gatineau, QC, CANADA;
2
Children's Hospital of Eastern Ontario, Regional Virology Laboratory, Ottawa, ON, CANA-
DA
Background
The unprecedented rate of mutation of HIV-1 and resulting antigenic heterogeneity among
the HIV viruses circulating throughout the world poses a significant challenge to vaccine
development. This study measures the immune response to a peptide-based vaccine
against variable regions of HIV with the belief that these regions represent areas in which
the virus is susceptible to immune recognition and elimination. We have synthesized and
evaluated the immunogenicity of a vaccine that contains a total of 176 lipidated and
non-lipidated peptide variants that represent 7 antigenically variable regions of the Env
and Gag proteins of HIV-1.
Objectives
To evaluate a vaccine strategy that targets only antigenically variable regions of HIV-1 Env
and Gag and to measure cellular immunity induced by the vaccine candidates.
Results
All animals had cellular immunity to naturally processed viral antigens. 3/6 animals had T
helper cell responses to Env proteins from multiple, divergent subtypes of HIV-1 (B, C, and
E); two additional animals recognized multiple distinct subtype B variants of HIV-1.
All animals had activated CD8+ T cells, measured both by intracellular IFN-g staining and
ELISPOT, that recognized naturally processed epitopes delivered by vaccinia constructs
encoding Env and Env/Gag/Pol proteins from multiple, divergent subtypes of HIV
(A, B, C, D, E. and F). Noteworthy was the ability of sera from one animal to neutralize
multiple, primary, T cell tropic isolates of HIV-1 (30% of the isolates tested). Vaccination of
HLA A*0201 transgenic mice with vaccine, followed by challenge with a recombinant
vaccinia vector expressing Env/Gag/Pol from a clade E strain of virus, resulted in a
two-log reduction in viral titers.
Conclusions
Our strategy is based on the belief that infection of humans with HIV-1 results in
immunity that while rarely protective, nonetheless creates strong negative pressure on
viral replication in vivo manifested as antigenic variation. This vaccine approach differs
starkly from current vaccine strategies that target conserved epitopes to achieve
cross-subtype immunological recognition of HIV-1.
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