Berkley, AM

Compton, AA

Connors, M

Duerr, A

Joshi, RP

McElrath, J

Migueles, SA

Rood, JE

English

PubMed

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Retrovirology
Open AccessOral presentation
0A07-01. HIV-specific CD8+ T-cells of vaccinees exhibit proliferative 
and cytotoxic capacities comparable to those of progressors
JE Rood*1, SA Migueles1, AM Berkley1, AA Compton1, RP Joshi1, A Duerr2, 
J McElrath2 and M Connors1
Address: 1NIH, Bethesda, MD, USA and 2Vaccine and Infectious Diseases Unit, Fred Hutchinson Cancer Research, Seattle, WA, USA
* Corresponding author    
Background
HIV-specific CD8+ T-cells of long-term nonprogressors
(LTNP) exhibit extraordinary per-cell cytotoxic capacity.
To adapt cytotoxicity assays for vaccine trials, we com-
pared HIV-specific CD8+ T-cell cytotoxic capacity with
proliferation and perforin expression using cells from
LTNP, viremic progressors, antiretroviral recipients with
<50 HIV RNA copies/ml plasma (Rx<50) and seronegative
individuals who had or had not received the Merck Ad5
trivalent vaccine.
Methods
HIV-specific CD8+ T-cell cytotoxic responses to HIVSF162-
infected CD4+ T-cell targets were measured at 1 hour by
flow cytometric detection of granzyme (Gr) B delivery to
live targets or infected CD4 elimination (ICE). Cytotoxic-
ity, IFN-γ production, perforin expression, and prolifera-
tion of HIV-specific CD8+ T-cells were examined following
a 6-day stimulation with HIVSF162-infected CD4+ T-cell tar-
gets.
Results
The HIV-specific CD8+ T-cell cytotoxic responses of vac-
cinees (medians 16.8% GrB activity, 37.2% ICE) were
clearly distinguishable from those of seronegative con-
trols (1.7% GrB activity, p < 0.001; 0.3% ICE, p < 0.001),
but were comparable to those of progressors (16.6% GrB
activity, p > 0.5; 37.4% ICE, p > 0.5). Among vaccinees,
those with the protective alleles HLA B*27, B*57, or B*58
tended to have higher responses. Vaccinee responses were
significantly less than those of LTNP (50.7% GrB activity,
p < 0.001; 82.5% ICE, p < 0.001). GrB activity and ICE
were strongly correlated with HIV-specific CD8+ T-cell
proliferation (R = 0.85, p < 0.001 and R = 0.87, p < 0.001,
respectively) and perforin expression (R = 0.86, p < 0.001
and R = 0.9, p < 0.001, respectively). When measured on
a per-cell basis, cytotoxicity of most vaccinees remained at
the level of progressors, even with higher effector:target
ratios.
Conclusion
GrB activity and ICE correlate strongly with CD8+ T-cell
proliferation and perforin expression in expanded cells
suggesting these parameters are reasonable surrogate
measurements of CD8+ T-cell-mediated killing requiring
fewer cells. GrB activity and ICE of vaccinees were similar
to those of progressors, suggesting these low responses
might contribute to suboptimal control in cases of HIV
infection following vaccination.
from AIDS Vaccine 2009
Paris, France. 19–22 October 2009
Published: 22 October 2009
Retrovirology 2009, 6(Suppl 3):O49 doi:10.1186/1742-4690-6-S3-O49
<supplement> <title> <p>AIDS Vaccine 2009</p> </title> <editor>Anna Laura Ross</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S3-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2105-10-S12-info.pdf</url> </supplement>
This abstract is available from: http://www.retrovirology.com/content/6/S3/O49
© 2009 Rood et al; licensee BioMed Central Ltd. 


0A07-01. HIV-specific CD8 T-cells of vaccinees exhibit proliferative and cytotoxic capacities comparable to those of progressors

JE Rood

SA Migueles

AM Berkley

AA Compton

RP Joshi

A Duerr

J McElrath

M Connors

Crossref

0A07-01. HIV-specific CD8+ T-cells of vaccinees exhibit proliferative and cytotoxic capacities comparable to those of progressors

McElrath J

Duerr A

Joshi RP

Compton AA

Berkley AM

Migueles SA

Rood JE

Connors M

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0A07-01. HIV-specific CD8+ T-cells of vaccinees exhibit proliferative and cytotoxic capacities comparable to those of progressors

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