Evidence for persistence of the SHIV reservoir early after MHC haploidentical hematopoietic stem cell transplantation.

Allogeneic transplantation (allo-HCT) has led to the cure of HIV in one individual, raising the question of whether transplantation can eradicate the HIV reservoir. To test this, we here present a model of allo-HCT in SHIV-infected, cART-suppressed nonhuman primates. We infect rhesus macaques with SHIV-1157ipd3N4, suppress them with cART, then transplant them using MHC-haploidentical allogeneic donors during continuous cART.

Combined OX40L and mTOR blockade controls effector T cell activation while preserving T reconstitution after transplant.

A critical question facing the field of transplantation is how to control effector T cell (T) activation while preserving regulatory T cell (T) function. Standard calcineurin inhibitor-based strategies can partially control T, but breakthrough activation still occurs, and these agents are antagonistic to T function. Conversely, mechanistic target of rapamycin (mTOR) inhibition with sirolimus is more T-compatible but is inadequate to fully control T activation.

Systems analysis uncovers inflammatory Th/Tc17-driven modules during acute GVHD in monkey and human T cells.

One of the central challenges of transplantation is the development of alloreactivity despite the use of multiagent immunoprophylaxis. Effective control of this immune suppression-resistant T-cell activation represents one of the key unmet needs in the fields of both solid-organ and hematopoietic stem cell transplant (HCT). To address this unmet need, we have used a highly translational nonhuman primate (NHP) model to interrogate the transcriptional signature of T cells during breakthrough acute graft-versus-host disease (GVHD) that occurs in the setting of clinically relevant immune suppression and compared this to the hyperacute GVHD, which develops in unprophylaxed or suboptimally prophylaxed transplant recipients.

Neither the HIV protease inhibitor lopinavir-ritonavir nor the antimicrobial trimethoprim-sulfamethoxazole prevent malaria relapse in plasmodium cynomolgi-infected non-human primates.

Plasmodium vivax malaria causes significant morbidity and mortality worldwide, and only one drug is in clinical use that can kill the hypnozoites that cause P. vivax relapses. HIV and P.

Using infective mosquitoes to challenge monkeys with Plasmodium knowlesi in malaria vaccine studies.

Background: When rhesus monkeys (Macaca mulatta) are used to test malaria vaccines, animals are often challenged by the intravenous injection of sporozoites. However, natural exposure to malaria comes via mosquito bite, and antibodies can neutralize sporozoites as they traverse the skin. Thus, intravenous injection may not fairly assess humoral immunity from anti-sporozoite malaria vaccines.