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No impact of humoral immune responses on controlling viremia during rhesus macaque infection with SIVsmm
Presented by Thaidra Gaufin, United States.
Gaufin T.1, Gautam R.1, Kasheta M.2, Barnes M.1, Carter A.C.1, Pattison M.1, Marx P.A.1, Kaur A.2, Pandrea I.1, Apetrei C.1
1Tulane National Primate Research Center, Covington, United States, 2New England Primate Research Center, Harvard Medical School, Southborough, United States
Objectives: Our group identified and characterized a SIVsmm strain (SIVsmmD215) that is highly susceptible to neutralization by autologous and heterologous sera and causes infection mimicking HIV-1 pathogenesis. We investigated the impact of humoral immune responses on SIVsmmD215 replication.
Methods: Eight Rh were inoculated with 100 TCID50 of SIVsmD215. Four were treated with 50 mg/kg of an anti-CD20 antibody (Rituxan, gift from Genentech, CA) at days –7, 14, 35, and 56 post-SIVsmmD215 infection. The others received only SIVsmmD215. The dynamics of viral load (VL) and major lymphocyte subsets were measured in peripheral blood, lymph nodes (LNs) and intestine. Serology was performed comparing the differences in the emergence of anti-SIV antibodies.
Results: The Rituxan group was successfully depleted of CD20 cells in the peripheral blood for 180 days post SIVsmmD215 infection. CD20 depletion affected the entire B cell lineage, illustrated by the low levels of CD79a in the blood, LN, and intestine. Two animals only partially depleted CD20 cells in the LNs and intestine. No significant differences in VLs were observed during either the acute or chronic phases: peak VLs ranged from 8 x 10^5 to 3 x 10^7 SIV RNA copies/ml in the CD20-depleted Rh and from 8 x 10^6 to 9 x 10^7 SIV RNA copies/ml in control Rh; while set point values ranged from 10^2 to 10^3 SIV RNA copies/ml. There was a tendency for lower set-point VLs in the CD20-depleted Rh compared to the control group. Seroconversion was delayed in animals having complete CD20 depletion in the LN and intestine.
Conclusions: 1. CD20 depletion plays no significant role in SIV viral replication control during the chronic stage of infection. 2. Although depletion is complete in the periphery in all the animals, the lack of antibody production is predicted by the efficacy of CD20 depletion at the main site of viral replication.
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