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Blood, 30 April 2009, Vol. 113, No. 18, pp. 4250-4261.
Prepublished online as a Blood First Edition Paper on January 23, 2009; DOI 10.1182/blood-2008-09-177741.


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IMMUNOBIOLOGY

Limited ability of humoral immune responses in control of viremia during infection with SIVsmmD215 strain

Thaidra Gaufin1,*, Rajeev Gautam1,*, Melissa Kasheta2, Ruy Ribeiro3, Erin Ribka4, Mary Barnes1, Melissa Pattison1, Coty Tatum1, Jeanne MacFarland1, David Montefiori5, Amitinder Kaur2, Ivona Pandrea6,7, and Cristian Apetrei1,8

1 Division of Microbiology, Tulane National Primate Research Center, Covington, LA; 2 Division of Immunology, New England Primate Research Center, Southborough, MA; 3 Theoretical Biology and Biophysics, Los Alamos National Laboratory, NM; 4 Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, LA; 5 Department of Surgery, Duke University, Durham, NC; 6 Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA; 7 Department of Pathology, School of Medicine, and 8 Department of Tropical Medicine, School of Public Health, Tulane University, New Orleans, LA

We investigated the impact of rhesus macaque (RM) B-cell depletion before inoculation with the isolate SIVsmmD215. Seven RMs were treated every 3 weeks with 50 mg/kg of an anti-CD20 antibody (rituximab) starting 7 days before inoculation for 2 (n = 4) and 5 (n = 3) months. Four control animals received no antibody. Three animals were completely depleted of CD20+ B cells, but 4 were only partially depleted of CD20 cells in the LNs and intestine. The decrease in antibody production was consistent with the efficacy of tissue CD20 depletion. Seroconversion and neutralizing antibody production was significantly delayed in animals showing complete tissue CD20 depletion and remained at low titers in all CD20-depleted RMs. Surprisingly, there was no significant difference in acute or chronic viral loads between CD20-depleted and control animal groups. There was a tendency for lower viral set points in CD20-depleted animals. At 6 weeks after inoculation, cellular immune responses were significantly stronger in CD20-depleted animals than in controls. There was no significant difference in survival between CD20-depleted and control animals. Our data suggest that a deficiency of Ab responses did not markedly affect viral replication or disease progression and that they may be compensated by more robust cellular responses.


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T. Gaufin, M. Pattison, R. Gautam, C. Stoulig, J. Dufour, J. MacFarland, D. Mandell, C. Tatum, M. H. Marx, R. M. Ribeiro, et al.
Effect of B-Cell Depletion on Viral Replication and Clinical Outcome of Simian Immunodeficiency Virus Infection in a Natural Host
J. Virol., October 15, 2009; 83(20): 10347 - 10357.
[Abstract] [Full Text] [PDF]



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