Abraham Research

Patton, J.B., S. Bonne-Année, J. Deckman, J.A. Hess, A. Torigian, T.J. Nolan, Z. Wang, S.A. Kliewer, A.C. Durham, J.J. Lee, M.L. Eberhard, D. J. Mangelsdorf, J. B. Lok, and D. Abraham. (2018) Methylprednisolone acetate induces, and Δ7-dafachronic acid suppresses, Strongyloides stercoralis hyperinfection in NSG mice. Proceedings of the National Academy of Sciences of the United States of America. 115: 204–209.

NSG mice, which have a reduced innate immune response and lack adaptive immunity, develop a complete infection with S. stercoralis and hyperinfection if treated with steroids. Treatment with Δ7-dafachronic acid, an agonist of the parasite nuclear receptor Ss-DAF-12, significantly reduced the worm burden in mice undergoing hyperinfection with S. stercoralis.

Patton, J.B., S. Bennuru, M.L. Eberhard, J.A. Hess, A. Torigian, S. Lustigman, T.B. Nutman and D. Abraham. (2018) Development ofOnchocerca volvulus in humanized NSG mice and detection of parasite biomarkers in urine and serum. PLOS Neglected Tropical Diseases. 12: e0006977.

We hypothesized that the addition of human cells to highly immunodeficient NSG mice would enhance parasite survival and development. In each of the humanized mouse models tested, worms matured and increased in length by up to 4-fold. O. volvulus proteins were observed in the serum and urine and represent potential biomarkers of infection and disease. 

Ryan, N.M., J.A. Hess, F. Pardo-Manuel de Villena, B. E. Leiby, A. Shimada, L. Yu, A. Yarmahmoodi, N. Petrovsky, B. Zhan, M.E. Bottazzi, B. L. Makepeace, S. Lustigman and D. Abraham. (2021) Onchocerca volvulus bivalent subunit vaccine induces protective immunity in genetically diverse Collaborative Cross recombinant inbred intercross mice. npj Vaccines. 6:17. DOI 10.1038/s41541-020-00276-2.

An Onchocerca volvulus vaccine, consisting of two recombinant antigens was evaluated in genetically diverse Collaborative Cross recombinant inbred intercross mice (CC-RIX). Equal and significant reductions in parasite survival were observed in 7 of 18 CC-RIX lines. Each line of mice had a unique set of immune responses to the vaccine, suggesting that the vaccine is polyfunctional. Vaccine efficacy in genetically diverse mice suggests that it will also be effective in genetically complex human populations.

Hess, J.A., M.L. Eberhard, M. Segura‑Lepe, K. Grundner‑Culemann, B. Kracher, J. Shryock, J. Harrington and D. Abraham. (2023) A rodent model for Dirofilaria immitis, canine heartworm: parasite growth, development, and drug sensitivity in NSG mice.Scientific Reports. 13: 976.

Immunodeficient NSG mice were susceptible to infection with Dirofilaria immitis, sustaining parasites for at least 15 weeks. Proteomic analysis of host responses to the infection revealed a complex pattern of changes after infection.  A susceptible isolate of D. immitis was killed by ivermectin whereas the resistant isolate had improved survival. NSG mice provide an ideal model for monitoring host responses to the infection and for testing parasites in vivo for susceptibility to direct chemotherapeutic activity.

Ryan, N.M., J.A. Hess, E.J. Robertson, N. Tricoche, C. Turner, J. Davis, N. Petrovsky, M. Ferguson, W.J. Rinaldi, V.M. Wong, A. Shimada, B. Zhan, M.E. Bottazzi, B.L. Makepeace, S.A. Gray, D. Carter, S. Lustigman, and D. Abraham. (2023) Adjuvanted fusion protein vaccine induces durable immunity to Onchocerca volvulus in mice and non-human primates. Vaccines, 11, 1212.

Mice and cynomolgus macaque non-human primates (NHPs) were immunized with a vaccine consisting of a fusion of two Onchocerca volvulus antigens and one of three different adjuvants. All vaccine formulations induced high antigen-specific antibody titers in both mice and NHPs. Passive transfer of sera from both mice and NHPs immunized with the fusion protein and the adjuvant AdvaxCpG transferred protection to naïve mice. These results demonstrate that the fusion protein with the adjuvant Advax-CpG induces durable protective immunity against O. volvulus in mice and NHPs that is mediated by vaccine-induced humoral factors.