Susceptibility to SIV Infection After Adenoviral Vaccination in a Low Dose Rhesus Macaque Challenge Model.

Authors:
Irene Bukh Brody
Irene Bukh Brody
Perelman School of Medicine
Philadelphia | United States
Roberto Calcedo
Roberto Calcedo
University of Pennsylvania
United States
Mary J Connell
Mary J Connell
School of Medicine
United States
Diane G Carnathan
Diane G Carnathan
University of Pennsylvania School of Medicine
United States
Martha Nason
Martha Nason
National Institutes of Health
United States
Benton O Lawson
Benton O Lawson
Emory Vaccine Center and Yerkes National Primate Research Center
Lawrenceville | United States
Surina Boyd
Surina Boyd
University of Pennsylvania
United States

Pathog Immun 2019 29;4(1):1-20. Epub 2019 Jan 29.

Department of Microbiology; Perelman School of Medicine, University of Pennsylvania; Philadelphia, Pennsylvania.

Background: Vaccination with the Merck human adenovirus serotype-5 (HAdV-5) vectored HIV-1 subtype B gag/pol/nef vaccine was unexpectedly associated with enhanced susceptibility to HIV-1 infection in uncircumcised HAdV-5 seropositive men. It has been hypothesized that vaccination may have resulted in activated CD4+ T lymphocytes trafficking to mucosal sites thereby increasing targets for HIV infection. We have previously shown that AdV-vector vacci-nation in rhesus macaques resulted in an increase in the frequency of activated mucosal CD4+ T cells. However, whether this increase in activation is sufficient to increase susceptibility to HIV/SIV infection is unclear.

Methods: To examine this scenario, we developed a preliminary, proof-of-concept vaccination-challenge model in order to examine vaccine-induced SIV susceptibility in rhesus macaques. Rhesus macaques (n = 10/group) were vaccinated with a simian AdV-7 (SAdV-7)-vector encoding an irrelevant insert (SARS spike) and challenged 5 weeks post-prime in an escalating dosing regimen starting with sub-infectious doses (1:10,000 or 2TCID) of SIVmac251.

Results: In contrast to our previous study, the SAdV-7 vaccine regimen did not induce detectable mucosal CD4+ T cell activation at the time points assessed in animals obtained from a different vendor and housed in a different facility. Within the power of the study, we did not observe significantly increased SIV acquisition in SAdV-7-vaccinated (5/10) versus placebo-vaccinated (3/10) macaques after repeated low-dose intra-rectal SIVmac251 challenge ( < 0.2).

Conclusions: These results lay groundwork for future experiments to assess vaccine-induced SIV susceptibility in rhesus macaques. Further larger-scale studies are necessary to confirm the AdV-vector vaccination associated trend towards increased SIV/HIV acquisition and clarify associated mechanisms.

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Source
http://dx.doi.org/10.20411/pai.v4i1.241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457171PMC
January 2019
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