The development of an effective AIDS vaccine remains one of the highest priorities in HIV-research. Because increasing evidence suggests that an effective vaccine will require both humoral and cellular immunity, this HIV-RAD project proposes to induce and measure both cellular and humoral immunity using plasmid DMAconstructs expressing SIV gag,-pol-env genes plus novel chemokine DNA plasmids to address mucosal cellular and humoral immunity. This proposal describes a new approach to inducing systemic and mucosal immunity. The overall objective of project #3 is to evaluate the potential of intramuscular (IM) delivery of chemokines to enhance mucosal immunity in the SIVmac model. The hypothesis to be tested is that chemokine-induced redirected trafficking of mucosal-homing immune cells to the systemic compartment leads to cellular and humoral mucosal immune responses without mucosal immunization. Mucosal-expressed chemokines CTACK, MECK, TECK will be tested for their individual potential to enhance the mucosal immune response of a systemically delivered SIV DNA vaccine. The vaccination approach will be IM co-immunization of macaques with an optimized SIVgag/pol/env plus each plasmid form of the mucosal-expressed chemokines.
The specific aims are: 1 A. To measure antigen specific cell mediated immune responses systemically in blood as well as in the mucosa following intramuscular plasmid co-immunization of rhesus macaques with 3 individual chemokines plus pSIVgag/pol/env.
This aim i s expanded to test 5 monkeys per group compared to 3 per group in the previous submission. 1B. To measure antigen specific antibody mediated immune responses systemically in blood and lymph node tissues as well as in the mucosa following IM co-immunization of rhesus macaques with individual chemokines plus pSIVgag/pol/env. Samples from animals in 1Awill also be provided to the University of Alabama Birmingham (DAB) group headed by Dr. Jiri Mestecky. 2. To carry out animal efficacy studies using the SIVmac-rhesus model to evaluate a) 1 selected chemokine adjuvant, b) pSIVgag/pol/env plus the control plasmid and c) a 3rd group of 8 will receive control plasmids only. All animals will be inoculated by the rectal route with pathogenic SIVmac251. Materials will be provided to investigators at the TNPRC, University of Pennsylvania (UPenn) and UAB.
This aim i s expanded to 8 animals per group to increase the statistical power of the experiment.
|Kutzler, M A; Wise, M C; Hutnick, N A et al. (2016) Chemokine-adjuvanted electroporated DNA vaccine induces substantial protection from simian immunodeficiency virus vaginal challenge. Mucosal Immunol 9:13-23|
|Villarreal, Daniel O; Weiner, David B (2015) IL-33 isoforms: their future as vaccine adjuvants? Expert Rev Vaccines 14:489-92|
|Wu, Stephan J; Villarreal, Daniel O; Shedlock, Devon J et al. (2015) Synthetic DNA approach to cytomegalovirus vaccine/immune therapy. Adv Exp Med Biol 848:131-48|
|Villarreal, Daniel O; Wise, Megan C; Siefert, Rebekah J et al. (2015) Ubiquitin-like Molecule ISG15 Acts as an Immune Adjuvant to Enhance Antigen-specific CD8 T-cell Tumor Immunity. Mol Ther 23:1653-62|
|Bukh, Irene; Calcedo, Roberto; Roy, Soumitra et al. (2014) Increased mucosal CD4+ T cell activation in rhesus macaques following vaccination with an adenoviral vector. J Virol 88:8468-78|
|Villarreal, Daniel O; Weiner, David B (2014) Interleukin 33: a switch-hitting cytokine. Curr Opin Immunol 28:102-6|
|Kalams, Spyros A; Parker, Scott D; Elizaga, Marnie et al. (2013) Safety and comparative immunogenicity of an HIV-1 DNA vaccine in combination with plasmid interleukin 12 and impact of intramuscular electroporation for delivery. J Infect Dis 208:818-29|
|Shedlock, Devon J; Aviles, Jenna; Talbott, Kendra T et al. (2013) Induction of broad cytotoxic T cells by protective DNA vaccination against Marburg and Ebola. Mol Ther 21:1432-44|
|Bao, Huihui; Ramanathan, Aarti A; Kawalakar, Omkar et al. (2013) Nonstructural protein 2 (nsP2) of Chikungunya virus (CHIKV) enhances protective immunity mediated by a CHIKV envelope protein expressing DNA Vaccine. Viral Immunol 26:75-83|
|Reuter, Morgan A; Yuan, Sally; Marx, Preston A et al. (2012) DNA-based HIV vaccines do not induce generalized activation in mucosal tissue T cells. Hum Vaccin Immunother 8:1648-53|
Showing the most recent 10 out of 26 publications