Person: Alpert, Michael
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Publication AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges
(2015) Gardner, Matthew R.; Kattenhorn, Lisa M.; Kondur, Hema R.; von Schaewen, Markus; Dorfman, Tatyana; Chiang, Jessica; Haworth, Kevin G.; Decker, Julie M.; Alpert, Michael; Bailey, Charles C.; Neale, Ernest S.; Fellinger, Christoph H.; Joshi, Vinita R.; Fuchs, Sebastian P.; Martinez-Navio, Jose M.; Quinlan, Brian D.; Yao, Annie Y.; Mouquet, Hugo; Gorman, Jason; Zhang, Baoshan; Poignard, Pascal; Nussenzweig, Michel C.; Burton, Dennis R.; Kwong, Peter D.; Piatak, Michael; Lifson, Jeffrey D.; Gao, Guangping; Desrosiers, Ronald; Evans, David T.; Hahn, Beatrice H.; Ploss, Alexander; Cannon, Paula M.; Seaman, Michael; Farzan, MichaelLong-term in vivo expression of a broad and potent entry inhibitor could circumvent the need for a conventional vaccine for HIV-1. Adeno-associated virus (AAV) vectors can stably express HIV-1 broadly neutralizing antibodies (bNAbs)1,2. However even the best bNAbs neutralize 10–50% of HIV-1 isolates inefficiently (IC80 > 5 μg/ml), suggesting that high concentrations of these antibodies would be necessary to achieve general protection3–6. Here we show that eCD4-Ig, a fusion of CD4-Ig with a small CCR5-mimetic sulfopeptide, binds avidly and cooperatively to the HIV-1 envelope glycoprotein (Env) and is more potent than the best bNAbs (geometric mean IC50 < 0.05 μg/ml). Because eCD4-Ig binds only conserved regions of Env, it is also much broader than any bNAb. For example, eCD4-Ig efficiently neutralized 100% of a diverse panel of neutralization-resistant HIV-1, HIV-2, and SIV isolates, including a comprehensive set of isolates resistant to the CD4-binding site bNAbs VRC01, NIH45-46, and 3BNC117. Rhesus macaques inoculated with an AAV vector stably expressed 17 to 77 μg/ml of fully functional rhesus eCD4-Ig for 40 weeks, and these macaques were protected from multiple infectious challenges with SHIV-AD8. Rhesus eCD4-Ig was also markedly less immunogenic than rhesus forms of four well characterized bNAbs. Our data suggest that AAV-delivered eCD4-Ig can function like an effective HIV-1 vaccine.
Publication Virtual Reality, Telemedicine, Web and Data Processing Innovations in Medical and Psychiatric Education and Clinical Care
(Springer Nature, 2006) Hilty, Donald; Alverson, Dale; Alpert, Michael; Tong, Lowell; Sagduyu, Kemal; Boland, Robert; Mostaghimi, Arash; Leamon, Martin; Fidler, Don; Yellowlees, PeterObjective This article highlights technology innovations in psychiatric and medical education, including applications from other fields.
Method The authors review the literature and poll educators and informatics faculty for novel programs relevant to psychiatric education.
Results The introduction of new technologies requires skill at implementation and evaluation to assess the pros and cons. There is a significant body of literature regarding virtual reality and simulation, including assessment of outcomes, but other innovations are not well studied.
Conclusions Innovations, like other uses of technology, require collaboration between parties and integration within the educational framework of an institution.