Project 1 will focus on the optimization of the next generation polyvalent Env HIV vaccine formulations using the multi-gene, polyvalent DMA prime - protein boost technology platform. Our first HIV vaccine formulation, DP6-001, was developed several years ago for a proof-of-concept trial to demonstrate the immunogenicity of the DMA prime - protein boost approach in human volunteers. The primary Env antigens isolated from HIV infected patients in mid-1990s were selected randomly based on their genetic clades. Rapid progress in the HIV vaccine field now provides us with a much larger selection of primary Env antigens, especially those Env proteins from clades less studied in the past and those Env proteins with more detailed information about the patients from whom the viruses were isolated. In addition, the recently developed pseudotyped neutralization assay and newly established target HIV-1 primary virus panel ("the Tiers System") provides a measurable standard to guide our selection of more relevant primary Env antigens for the development of HIV vaccines focusing on the induction of neutralizing antibody responses. By taking advantage of the above progress, we have identified a group of primary Env antigens that were able to elicit much broader neutralizing antibodies than those included in our previous formulation DP6-001. In the current Project 1 of this IPCAVD program, the following studies will be conducted:
Aim 1 To finalize the selection of next generation polyvalent Env formulation to further improve the quality of neutralizing antibody activities.
Aim 2 To select an immunogenic adjuvant to be used as part of the protein boost for the next generation polyvalent Env formulation.
Aim 3 To test the immunogenicity of next generation polyvalent Env formulation when the DMA priming is delivered by the electroporation method.
Aim 4 To examine the epitope profiles in immune sera elicited by DMA prime-protein boost approach and identify the epitope specificities of antibodies responsible for the neutralizing activities.
|Suschak, John J; Wang, Shixia; Fitzgerald, Katherine A et al. (2015) Identification of Aim2 as a sensor for DNA vaccines. J Immunol 194:630-6|
|Pouliot, Kimberly; Buglione-Corbett, Rachel; Marty-Roix, Robyn et al. (2014) Contribution of TLR4 and MyD88 for adjuvant monophosphoryl lipid A (MPLA) activity in a DNA prime-protein boost HIV-1 vaccine. Vaccine 32:5049-56|
|Chen, Yuxin; Vaine, Michael; Wallace, Aaron et al. (2013) A novel rabbit monoclonal antibody platform to dissect the diverse repertoire of antibody epitopes for HIV-1 Env immunogen design. J Virol 87:10232-43|
|Buglione-Corbett, Rachel; Pouliot, Kimberly; Marty-Roix, Robyn et al. (2013) Serum cytokine profiles associated with specific adjuvants used in a DNA prime-protein boost vaccination strategy. PLoS One 8:e74820|
|Pan, Ruimin; Sampson, Jared M; Chen, Yuxin et al. (2013) Rabbit anti-HIV-1 monoclonal antibodies raised by immunization can mimic the antigen-binding modes of antibodies derived from HIV-1-infected humans. J Virol 87:10221-31|
|Marty-Roix, Robyn; Lien, Egil (2013) (De-) oiling inflammasomes. Immunity 38:1088-90|
|Wang, Zheng; Zhang, Mingshun; Wang, Yan et al. (2011) A versatile vector for the production of pseudotyped viruses expressing gp120 antigens from different clades of primary HIV-1 isolates. J Virol Methods 171:183-9|
|Vaine, Michael; Duenas-Decamp, Maria; Peters, Paul et al. (2011) Two closely related Env antigens from the same patient elicited different spectra of neutralizing antibodies against heterologous HIV-1 isolates. J Virol 85:4927-36|
|Zolla-Pazner, Susan; Kong, X-P; Jiang, Xunqing et al. (2011) Cross-clade HIV-1 neutralizing antibodies induced with V3-scaffold protein immunogens following priming with gp120 DNA. J Virol 85:9887-98|
|Vaine, Michael; Wang, Shixia; Hackett, Anthony et al. (2010) Antibody responses elicited through homologous or heterologous prime-boost DNA and protein vaccinations differ in functional activity and avidity. Vaccine 28:2999-3007|
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