This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This program will design and develop a series of potent and highly selective protein-based topical microbicides. The unifying theme of the program is the use of non-pathogenic mucosal bacteria, lactobacilli, to deliver these proteins to mucosal surfaces within the vagina and rectum. The administration of genetically modified vaginal isolates of lactobacilli, expressing protein microbicides, is anticipated to prevent access or entry of HIV into host cells and tissues, thereby reducing infection. The product development projects are supported by central core facilities, including administrative, microbiology, and primate safety study cores. In addition to product safety studies conducted in macaques, optimization of colonization conditions and histological evaluation of Lactobacillus association with the vaginal mucosal will be carried out. Determination of an adequate dosing regimen for the bioengineered Lactobacillus will be essential for determining the safety profile of the microbicides, and will address whether there are any unexpected effects of microbicides produced by lactobacilli on vaginal epithelia. Importantly the three unique product development projects highlighted in this application have already completed key 'proof-of-concept' studies that set the stage for advanced research and development activities. Furthermore, all three approaches target conserved functional mechanisms used by HIV to achieve a productive infection of its host. As such, these approaches are less likely to be circumvented by the high mutability of viral proteins, an important property of HIV that has impaired the development of effective preventative vaccines.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
2P51RR000166-46
Application #
7562726
Study Section
Special Emphasis Panel (ZRR1-CM-8 (02))
Project Start
2007-07-05
Project End
2008-04-30
Budget Start
2007-07-05
Budget End
2008-04-30
Support Year
46
Fiscal Year
2007
Total Cost
$434,134
Indirect Cost
Name
University of Washington
Department
Type
Other Domestic Higher Education
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Pham, Amelie; Carrasco, Marisa; Kiorpes, Lynne (2018) Endogenous attention improves perception in amblyopic macaques. J Vis 18:11
Zanos, Stavros; Rembado, Irene; Chen, Daofen et al. (2018) Phase-Locked Stimulation during Cortical Beta Oscillations Produces Bidirectional Synaptic Plasticity in Awake Monkeys. Curr Biol 28:2515-2526.e4
Choi, Hannah; Pasupathy, Anitha; Shea-Brown, Eric (2018) Predictive Coding in Area V4: Dynamic Shape Discrimination under Partial Occlusion. Neural Comput 30:1209-1257
Shushruth, S; Mazurek, Mark; Shadlen, Michael N (2018) Comparison of Decision-Related Signals in Sensory and Motor Preparatory Responses of Neurons in Area LIP. J Neurosci 38:6350-6365
Raghanti, Mary Ann; Edler, Melissa K; Stephenson, Alexa R et al. (2018) A neurochemical hypothesis for the origin of hominids. Proc Natl Acad Sci U S A 115:E1108-E1116
Wool, Lauren E; Crook, Joanna D; Troy, John B et al. (2018) Nonselective Wiring Accounts for Red-Green Opponency in Midget Ganglion Cells of the Primate Retina. J Neurosci 38:1520-1540
Hasegawa, Yu; Curtis, Britni; Yutuc, Vernon et al. (2018) Microbial structure and function in infant and juvenile rhesus macaques are primarily affected by age, not vaccination status. Sci Rep 8:15867
Oleskiw, Timothy D; Nowack, Amy; Pasupathy, Anitha (2018) Joint coding of shape and blur in area V4. Nat Commun 9:466
Eberle, R; Jones-Engel, L (2017) Understanding Primate Herpesviruses. J Emerg Dis Virol 3:
McAdams, Ryan M; McPherson, Ronald J; Kapur, Raj P et al. (2017) Focal Brain Injury Associated with a Model of Severe Hypoxic-Ischemic Encephalopathy in Nonhuman Primates. Dev Neurosci 39:107-123

Showing the most recent 10 out of 320 publications