Anti-HFRS Human IgG Produced in Transchromosomic Bovines Has Potent Hantavirus Neutralizing Activity and Is Protective in Animal Models.

We explored an emerging technology to produce anti-Hantaan virus (HTNV) and anti-Puumala virus (PUUV) neutralizing antibodies for use as pre- or post-exposure prophylactics. The technology involves hyperimmunization of transchomosomic bovines (TcB) engineered to express human polyclonal IgG antibodies with HTNV and PUUV DNA vaccines encoding GG glycoproteins. For the anti-HTNV product, TcB was hyperimmunized with HTNV DNA plus adjuvant or HTNV DNA formulated using lipid nanoparticles (LNP).

Lymphoid and Myeloid Recovery in Rhesus Macaques Following Total Body X-Irradiation.

Recovery from severe immunosuppression requires hematopoietic stem cell reconstitution and effective thymopoiesis to restore a functional immune cell repertoire. Herein, a model of immune cell reconstitution consequent to potentially lethal doses of irradiation is described, which may be valuable in evaluating potential medical countermeasures. Male rhesus macaques were total body irradiated by exposure to 6.

Immune cell reconstitution after exposure to potentially lethal doses of radiation in the nonhuman primate.

Delayed immune reconstitution remains a major cause of morbidity associated with myelosuppression induced by cytotoxic therapy or myeloablative conditioning for stem cell transplant, as well as potentially lethal doses of total- or partial-body irradiation. Restoration of a functional immune cell repertoire requires hematopoietic stem cell reconstitution for all immune cells and effective thymopoiesis for T cell recovery. There are no medical countermeasures available to mitigate damage consequent to high-dose, potentially lethal irradiation, and there are no well characterized large animal models of prolonged immunosuppression to assess efficacy of potential countermeasures.

Filgrastim improves survival in lethally irradiated nonhuman primates.

Treatment of individuals exposed to potentially lethal doses of radiation is of paramount concern to health professionals and government agencies. We evaluated the efficacy of filgrastim to increase survival of nonhuman primates (NHP) exposed to an approximate mid-lethal dose (LD(50/60)) (7.50 Gy) of LINAC-derived photon radiation.

A nonhuman primate model of the hematopoietic acute radiation syndrome plus medical management.

The development of medical countermeasures against the hematopoietic subsyndrome of the acute radiation syndrome requires well characterized and validated animal models. The model must define the radiation dose- and time-dependent relationships for mortality and major signs of morbidity to include other organ damage that may contribute to morbidity and mortality. Herein, the authors define these parameters for a nonhuman primate exposed to total body radiation and administered medical management.