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Wilson Progress Report Abstracts continued 

 
Submitted July 1, 2010

The goal of this project is to (a) understand the biology of gut-associated lymphocytes (GALT) in the human gastro-intestinal tract with respect to their reactivity to adenovirus antigens, especially as it pertains to gay men and (b) to model the fate of GALT (in macaques) following vaccination with adenovirus vaccines using adenoviruses obtained from macaques in order to determine whether this might lead to a possible increased susceptibility to HIV infection. In the first part of the study, we have shown that GALT obtained from normal healthy macaques show a measurable albeit low memory response to adenovirus antigens. An important goal of this project is to create an SIV challenge model in macaques where the immunizing vector is a macaque adenovirus (and not a human adenovirus vector, as has been done before) because the T-cell response to a macaque adenovirus against which a recall reaction may be mounted may be different than when using an adenovirus that the macaque has not previously “seen”. We have isolated and sequenced 12 adenoviruses from macaques and are currently creating vectors. In a second part of the study we have vaccinated 12 rhesus macaques with an adenovirus vector that was constructed from a macaque adenovirus (and 5 macaques with a conventional HAdV-5 vector) with the intent to obtain serial rectal mucosal biopsies in order to study the status of the T-cells in the gut with respect to their reactivity to adenoviral antigens. We have obtained samples from the first few weeks and have observed a large increase in adenovirus-reactive T cells in the rectal mucosa. We are continuing to obtain mucosal biopsies from these animals to delineate the kinetics of the responses and determine differences if any in responses to the macaque and the human adenovirus vector.

 
Submitted October 16, 2009 (Interim Report)

The goal of this project is to (a) understand the biology of gut-associated lymphocytes (GALT) in
the human gastro-intestinal tract with respect to their reactivity to adenovirus antigens,
especially as it pertains to gay men and (b) to model the fate of GALT (in macaques) following
vaccination with adenovirus vaccines using adenoviruses obtained from macaques in order to
determine whether this might lead to a possible increased susceptibility to HIV infection.
In the first part of the study, we have obtained GI tissues from eight macaques and have
extensively defined the status of GALT with respect to their ability to be stimulated by
adenovirus antigens, using an adenovirus that we have found to be endemic in captive
macaque colonies in the US. Additionally, we have analyzed the mononuclear cells present in
the blood from twenty-five macaques and have analyzed their capacity to be stimulated by a
selection of adenoviruses belonging to different species originally isolated from humans,
chimpanzees, and macaques. Both these data sets have shown that macaques show a
measurable albeit low memory response to adenovirus antigens. Importantly, we have also
validated the reagents and assays that were part of this determination because they will be
used to determine the change in reactivity that may occur following vaccination.
An important goal of this project is to create an SIV challenge model in macaques where the
immunizing vector is a macaque adenovirus (and not a human adenovirus vector, as has been
done before) because the T-cell response to a macaque adenovirus against which a recall
reaction may be mounted may be different than when using an adenovirus that the macaque
has not previously “seen”. We have previously observed that macaques chronically shed
adenovirus DNA in their stools, although the frequency with which these viruses can be cultured
is quite low. In this project we aim to isolate and sequence 12 macaque adenoviruses from stool
cultures and to construct vectors using three of them. We have so far obtained 6 adenoviruses
in this manner that may be vectored and have begun to sequence 3 additional adenoviruses.

 
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