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

Abstract

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. (Blood. 2009; 113:4250-4261)

Effect of B-Cell Depletion on Viral Replication and Clinical Outcome of Simian Immunodeficiency Virus Infection in a Natural Host

“…In our previous study of CD20 ϩ B-cell depletion in RMs infected with SIVsmmD215, we observed that the ablation of humoral immune responses was predicted by the efficacy of B-cell depletion in tissues (18). We therefore examined the changes in the B-cell populations in tissues in rituximab-infused and control AGMs.…”

“…However, these studies used strains that are highly resistant to neutralization (SIVmac251 and SIVmac239), making it difficult to assess the role that antibodies have in controlling SIV replication and disease progression. Moreover, our recent results suggested a limited impact of humoral immune responses in controlling replication of a neutralization-sensitive SIVsmm strain in rhesus macaques (18).…”

T-bet+ B cells are induced by human viral infections and dominate the HIV gp140 response

“…An important question remaining is the degree to which T-bet + B cells and derived antibodies contribute to control of viremia during HIV and other viral infections. Indeed, while a murine study demonstrated the requirement of T-bet + B cells to control chronic LCMV viremia to low levels (6), the role of B cells and Ig in ongoing control of HIV/SIV remains controversial (74)(75)(76)(77)(78). However, it is highly likely that an efficacious HIV vaccine will need to induce HIV Env-specific broadly neutralizing antibodies.…”

Mucosal Simian Immunodeficiency Virus Transmission in African Green Monkeys: Susceptibility to Infection Is Proportional to Target Cell Availability at Mucosal Sites

“…Cells were filtered through nylon bags and washed with RPMI medium (Cellgro, Manassas, VA) containing 5% heat-inactivated newborn calf serum, 0.01% penicillin-streptomycin, 0.01% L-glutamine, and 0.01% HEPES buffer, as previously described (48,51). Lymphocyte separation from pinch biopsy specimens was done as previously described (17,50,51,55). Briefly, intestinal biopsy specimens were digested using EDTA followed by collagenase, and cells were then isolated using Percoll density gradient centrifugation (50,51,55).…”