Betts, MR

Carnathan, D

Casimiro, DR

Cox, K

Dubey, S

Ertl, HC

Hutnick, N

Ratcliffe, S

Robertson, MN

English

PubMed

N Hutnick

D Carnathan

S Dubey

K Cox

S Ratcliffe

MN Robertson

DR Casimiro

HC Ertl

MR Betts

Crossref

BioMed Central
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Retrovirology
Open AccessPoster presentation
P16-09. Adenovirus 5 vector HIV vaccination does not affect 
mucosal homing markers on Ad5-specific CD4+ T-cells in humans
N Hutnick*1, D Carnathan1, S Dubey2, K Cox2, S Ratcliffe1, MN Robertson2, 
DR Casimiro2, HC Ertl3 and MR Betts1
Address: 1Microbiology, University of Pennsylvania, Philadelphia, PA, USA, 2Merck Research Laboratories, West Point, PA, USA and 3Wistar 
Institute, Philadelphia, PA, USA
* Corresponding author    
Background
The reasons for the recent failure of the Merck STEP trial,
wherein Ad5-seropositive subjects demonstrated
increased susceptibility to HIV infection, remain unclear.
One potential hypothesis is that expansion and mucosal
trafficking of Ad5-specific CD4+ T cells following Ad-vec-
tor immunization possibly rendered vaccinees more sus-
ceptible to HIV infection.
Methods
Ad-specific T cell responses were characterized in five sero-
positive and seronegative subjects from the Merck phase I
016 trial, the immediate STEP trial predecessor. Subjects
received 3 × 1011 vector particles Merck Ad5 gag/pol/nef
at weeks 0, 4 and 30. PBMC samples were obtained at
weeks 0, 4, 8,18, 26, 30, 42, 52 and 78 relative to vaccina-
tion. T-cell responses to Ad were measured by stimulating
PBMCs overnight with whole Ad vector before measuring
functionality (IFN-γ, TNF-α, IL-2) memory phenotype
(CD45RO, CCR7) and mucosal homing markers (α4, β7,
CCR10, αE) by multicolor flow cytometry.
Results
There was no difference in the % of total or Ad-specific
α4+β7+ CD4+ T-cells between seronpositive and seroneg-
ative subjects. There was also no increase in total or Ad-
specific α4+β7+ CD4+ T-cells following vaccination. Ad-
specific CD4+ T-cells comprised only 1–2% of total
α4+β7+ cells in the blood. The memory phenotype of
α4+β7+ was mixed between central memory, effector
memory and effector CD4+ T-cells in both serogroups
with no change in memory phenotype observed upon
vaccination. CCR10 and CD103 were expressed at mar-
ginal levels on Ad-specific CD4+ T cells.
Conclusion
This data suggests that vaccination does not induce a dif-
ferential measurable effect on mucosal trafficking in circu-
lating Ad-specific CD4+ T cells between the serogroups
and therefore contradicts a role for Ad-specific T-cells in
the possible increased risk of HIV infection observed dur-
ing the STEP trial.
from AIDS Vaccine 2009
Paris, France. 19–22 October 2009
Published: 22 October 2009
Retrovirology 2009, 6(Suppl 3):P238 doi:10.1186/1742-4690-6-S3-P238
<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/P238
© 2009 Hutnick et al; licensee BioMed Central Ltd. 


P16-09. Adenovirus 5 vector HIV vaccination does not affect mucosal homing markers on Ad5-specific CD4+ T-cells in humans

Ertl HC

Casimiro DR

Robertson MN

Ratcliffe S

Cox K

Dubey S

Carnathan D

Hutnick N

Betts MR

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P16-09. Adenovirus 5 vector HIV vaccination does not affect mucosal homing markers on Ad5-specific CD4+ T-cells in humans

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