Increased mucosal CD4+ T cell activation in rhesus macaques following vaccination with an adenoviral vector.
The possibility that vaccination with adenovirus (AdV) vectors increased mucosal T cell activation remains a central hypothesis to explain the potential enhancement of HIV acquisition within the Step trial. Modeling this within rhesus macaques is complicated because human adenoviruses, including human adenovirus type 5 (HAdV-5), are not endogenous to macaques. Here, we tested whether vaccination with a rhesus macaque-derived adenoviral vector (simian adenovirus 7 [SAdV-7]) enhances mucosal T cell activation within rhesus macaques. Following intramuscular SAdV-7 vaccination, we observed a pronounced increase in SAdV-7-specific CD4(+) T cell responses in peripheral blood and, more dramatically, in rectal mucosa tissue. Vaccination also induced a significant increase in the frequency of activated memory CD4(+) T cells in SAdV-7- and HAdV-5-vaccinated animals in the rectal mucosa but not in peripheral blood. These fluctuations within the rectal mucosa were also associated with a pronounced decrease in the relative frequency of naive resting CD4(+) T cells. Together, these results indicate that peripheral vaccination with an AdV vector can increase the activation of mucosal CD4(+) T cells, potentially providing an experimental model to further evaluate the role of host-vector interactions in increased HIV acquisition after AdV vector vaccination.


OBJECTIVE
The possibility that vaccination with a human adenovirus 5 vector increased mucosal T cell activation remains a central hypothesis to explain the potential enhancement of human immunodeficiency virus (HIV) acquisition within the Step trial. In this study, we tested whether vaccination with a rhesus macaque-derived adenoviral vector in rhesus macaques enhances mucosal CD4(+) T cell activation, the main cell target of simian immunodeficiency virus (SIV)/HIV. The results showed that vaccination with an adenoviral vector indeed increases activation of mucosal CD4(+) T cells and potentially increases susceptibility to SIV infection.
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Irene
I
Bukh
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Roberto
R
Calcedo
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Soumitra
S
Roy
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Diane G
DG
Carnathan
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Rebecca
R
Grant
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Qiuyue
Q
Qin
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Surina
S
Boyd
Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Sarah J
SJ
Ratcliffe
University Laboratory Animal Resources, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Christin L
CL
Veeder
Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Scarlett L
SL
Bellamy
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Michael R
MR
Betts
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA wilsonjm@mail.med.upenn.edu.
James M
JM
Wilson
D000261:Adenoviruses, Simian / Q000276:immunology*; D000818:Animals; D001769:Blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005822:Genetic Vectors / Q000276:immunology*; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000276:immunology; D008253:Macaca mulatta; D012007:Rectum / Q000276:immunology; D014611:Vaccination / Q000379:methods