This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. E2DISP, an engineered protein domain from Geobacillus stearothermophilus pyruvate dehydrogenase subunit E2, can be used to express N-terminal fusions of heterologous peptides or proteins. E2DISP self-assembles into 24 nm virus like particles (VLPs) displaying up to 60 copies of a foreign antigen.
The aims are to: (1) Design HIV-E2 Envelope (Env) fusion proteins with conserved neutralization determinants and determine their effectiveness in eliciting neutralizing antibodies (NAbs);(2) Explore immunization strategies to elicit long lasting Th1 CD4, CTL memory responses while preserving sustained antibody responses; (3) Explore optimal presentation and co-administration of E2DISP VLPs with recombinant C3d-based adjuvants;and (4) Optimize the use of pure and hybrid E2-HIV VLPs in prime-boost regimens with other vaccine delivery systems effective in boosting cellular immunity and NAb responses. In the last year, we have developed effective methods for purifying and stabilizing pure and hybrid particles and have shown that mice immunized with the Gag-E2 and Env-E2 VLPs elicit CD8+ T cell responses. In experiments in rabbits using HIV Env fusion protein 60-mer particles, we have been successful in showing the development of high titers of neutralizing antibodies within only six weeks, after two immunizations with DNA and E2 protein VLPs. Both the V3 region as well as portions of the gp41 protein elicit neutralizing antibodies in rabbits, and we are exploring the breadth of this response. We are also exploring the delivery of these fusion proteins with microneedle delivery to the mucosal antigen-presenting cells.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000163-52
Application #
8357780
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
52
Fiscal Year
2011
Total Cost
$194,877
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Su, Weiping; Foster, Scott C; Xing, Rubing et al. (2017) CD44 Transmembrane Receptor and Hyaluronan Regulate Adult Hippocampal Neural Stem Cell Quiescence and Differentiation. J Biol Chem 292:4434-4445
Lima, Fernanda B; Leite, Cristiane M; Bethea, Cynthia L et al. (2017) Progesterone increased ?-endorphin innervation of the locus coeruleus, but ovarian steroids had no effect on noradrenergic neurodegeneration. Brain Res 1663:1-8
Slayden, Ov Daniel (2016) Translational In Vivo Models for Women's Health: The Nonhuman Primate Endometrium--A Predictive Model for Assessing Steroid Receptor Modulators. Handb Exp Pharmacol 232:191-202
Chadderdon, S M; Belcik, J T; Bader, L et al. (2016) Vasoconstrictor eicosanoids and impaired microvascular function in inactive and insulin-resistant primates. Int J Obes (Lond) 40:1600-1603
Dufour, Brett D; McBride, Jodi L (2016) Intravascular AAV9 Administration for Delivering RNA Silencing Constructs to the CNS and Periphery. Methods Mol Biol 1364:261-75
Meyer, Thomas J; Held, Ulrike; Nevonen, Kimberly A et al. (2016) The Flow of the Gibbon LAVA Element Is Facilitated by the LINE-1 Retrotransposition Machinery. Genome Biol Evol 8:3209-3225
Pleil, Kristen E; Helms, Christa M; Sobus, Jon R et al. (2016) Effects of chronic alcohol consumption on neuronal function in the non-human primate BNST. Addict Biol 21:1151-1167
Mohiuddin, Muhammad M; Singh, Avneesh K; Corcoran, Philip C et al. (2016) Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft. Nat Commun 7:11138
Sylwester, Andrew; Nambiar, Kate Z; Caserta, Stefano et al. (2016) A new perspective of the structural complexity of HCMV-specific T-cell responses. Mech Ageing Dev 158:14-22
Laws, L H; Parker, C E; Cherala, G et al. (2016) Inflammation Causes Resistance to Anti-CD20-Mediated B Cell Depletion. Am J Transplant 16:3139-3149

Showing the most recent 10 out of 481 publications