Oral Abstract Session 01 - Global HIV Vaccine Enterprise

POSTERS
Posters
Topic 11: T Cell Immunity
P11.11
The Recognition of HIV-1 Consensus Group M Gag
and Nef Peptide Reagents in Mono- and Multi-clade
Epidemics: Implications for HIV Vaccine Design
L. Zembe 1 , M. Tongo 2 , E. Ebong 3 , E.M. Ngobe 3 , C. Williamson 2 ,
W. Burgers 2
1 University of Cape Town, Cape Town, South Africa; 2 Division
of Virology, University of Cape Town, Cape Town, South Africa;
3 Institute of Medical Research and Study of Medicinal Plants,
Younde, Cameroon
Background: The high level of genetic diversity of HIV-1 poses a
major challenge for global vaccine development. Vaccines based
on centralized sequences would minimize genetic distances
to multiple clades and potentially maximize cross-reactivity.
Whether reactivity of these centralized peptide reagents differs
in mono- and multi-clade epidemic is unknown.
Methods: In this study, full-length gag and nef gene sequences
(from Cameroon, 50 and 54, respectively and South Africa, 23 and
19, respectively) were characterized. HIV-specific T-cell responses
to group M consensus Gag and Nef peptide reagents were
characterized at the peptide level using the IFN-γ ELISpot assay.
Results: Viruses from Cameron exhibited a large degree of
genetic diversity; all subtypes were present excluding subtype
C, with CRF02_AG being dominating (49%). Contrary, sequenced
viruses from South Africa were all pure subtype C viruses.
Despite the greater diversity of viral clades in the Cameroonian
cohort, the genetic distances to the consensus M reagents
was similar for both cohorts (11% and 15% for Gag and Nef,
respectively). Whilst the magnitude and breadth of responses
to Con M Gag and Nef did not differ significantly between the
two cohorts, there was a greater frequency of responders in the
Cameroonian cohort compared to South Africans (95% versus
82%, respectively). For the Cameroonian cohort, 75/182 (41%)
of the consensus M peptides were targeted, while for the South
African cohort 66/182 (36%) of the peptides were targeted, with
the majority being recognized in only 1-2 participants (69% and
76%, respectively). Patterns of immunodominance and targeting,
however, differed dramatically between the two cohorts, with
only 36% and 39% of Gag and Nef peptides commonly recognized
between the two cohorts.
Conclusion: Although similarities in total magnitude and breadth
may be observed between different epidemics, patterns of
immunodominance of centralized immunogens may be different
which may have implications for vaccine development.
222
AIDS Vaccine 2012
P11.12
Programmed Death-1(PD-1), a Correlate of
Protection Against Disease Progression in HIV-1
Infected Long-Term Non-Progressors
J. Kyosiimire-Lugemwa 1
1 MRC/UVRI Uganda Research Unit on AIDS, Kampala, Uganda
Background: Long-Term Non-Progressors (LTNP) control HIV-
1 disease progression but correlates of control are not clear.
T-cell activation and expression of Programmed Death-1 (PD-1),
a marker of T-cell inhibition/exhaustion, have been suggested
as markers of progression to AIDS. We assessed levels of T-cell
activation and PD-1 in LTNP and Rapid progressors (RP).
Methods: We recruited 15 LTNP and 15 RP originally enrolled in
the Entebbe Cohort in Uganda. All were ART naïve and 29 were
women. HLADR, CD38 and PD-1 levels were assessed in CD4, CD8
and CD45RA T-cells by flow cytometry. HIV-1 disease progression
markers: plasma lipopolysaccharide (LPS) levels, HIV-1 RNA viral
load (VL), HIV-1 pro-viral DNA load (PVL) and CD4 counts at
enrollment were quantified. Comparisons between groups were
performed using the Mann-Whitney U test and correlations by
Spearman’s linear correlation coefficients.
Results: Activated (HLADR+CD38+) CD4+CD45RA+ were higher
in the LTNP (median 0.64% for LTNP and 0.18% for RP, p=0.03).
PD-1 expression in the CD4 and CD8 T-cell subsets was higher in
the LTNP (CD4+PD-1+ median 39.6% for LTNP and 1.0% for RP,
p=0.001; CD8+PD-1+ median 60.8% for LTNP and 13.5% for RP,
p=0.003). VL (p=0.05), PVL (p=0.03), LPS (p=0.005) were higher
in the RP and enrollment CD4 count (p=0.0002) was higher
in the LTNP. VL, PVL and LPS positively associated with each
other and all negatively associated with enrollment CD4 count.
CD4+PD-1+ correlated negatively with VL (rs=-0.40, p=0.03),
LPS (rs=-0.38, p=0.04) and positively with enrollment CD4 count
(rs=0.36, p=0.05). CD4+CD45RA+HLADR+CD38+ correlated
positively with enrollment CD4 counts (rs=0.38, p=0.04).
Positive correlations were observed between CD4+CD45RA+/-
HLADR+CD38+, CD8+CD45RA+HLADR+CD38+ and CD4+PD-1+
and CD8+PD-1+ T-cells.
Conclusion: Co-expression of PD-1 and activation markers was
higher in the LTNP compared to the RP, contrary to other studies.
PD-1 correlated with markers of protection against HIV-1 disease
progression, suggesting a beneficial role for PD-1.