The long term objective of this research is to produce an effective vaccine to protect humans from HIV-1 infection. HIV-1 presents several challenges to vaccine design: (1) high mutation rates result in tremendous diversity of virus envelope, the target of neutralizing antibody, such that antibody elicited to one envelope may not protect from virus with a distinct envelope; (2) envelope directly from infected persons differ from envelopes obtained from T-cell line cultures, the usual source of envelope for vaccines; (3) envelope glycoprotein exists as oligomers on the virion surface, not as monomers in previous vaccines. To address these challenges we proposed to deliver diverse, oligomeric, patient-derived envelopes to induce multiple type-specific responses capable of recognizing native envelope on natural variants. To recruit these array of long-lived B and T cells we propose a 3- tiered sequential vaccine strategy: () DNA vaccine priming-> (2) live vector vaccination->(3) purified protein boosting. These 3 alternate moieties are selected to trigger helper T cells, cytotoxic T cells and B cells, each considered important correlates of protection. Studies proposed here focus first on Phase I trials on a multi-envelope recombinant vaccinia virus vaccine (PolyEnv1) which is central to this approach (aims 1-3) followed by introduction of DNA priming and protein boosting (aim 4).
Specific aims are:
Aim 1. Determine the safety of PolyEnv1, a novel multi-envelope recombinant vaccinia virus vaccine.
Aim 2. Characterize the envelope-specific humoral response induced in the Phase I study of PolyEnv1.
Aim 3 : Characterize the envelope-specific cellular immune responses elicited in the Phase I study of PolyEnv1.
Aim 4. Determine the safety and immunogenicity of a multi-envelope DNA vaccine and a recombinant gp140 protein vaccine.

Project Start
2002-05-01
Project End
2003-04-30
Budget Start
Budget End
Support Year
4
Fiscal Year
2002
Total Cost
Indirect Cost
Name
St. Jude Children's Research Hospital
Department
Type
DUNS #
067717892
City
Memphis
State
TN
Country
United States
Zip Code
38105
Sealy, Robert E; Jones, Bart G; Surman, Sherri L et al. (2016) Murine Monoclonal Antibodies for Antigenic Discrimination of HIV-1 Envelope Proteins. Viral Immunol 29:64-70
Jones, Bart G; Sealy, Robert E; Zhan, Xiaoyan et al. (2012) UV-inactivated vaccinia virus (VV) in a multi-envelope DNA-VV-protein (DVP) HIV-1 vaccine protects macaques from lethal challenge with heterologous SHIV. Vaccine 30:3188-95
Hurwitz, Julia L (2011) Respiratory syncytial virus vaccine development. Expert Rev Vaccines 10:1415-33
Surman, Sherri L; Rudraraju, Rajeev; Woodland, David L et al. (2011) Clonally related CD8+ T cells responsible for rapid population of both diffuse nasal-associated lymphoid tissue and lung after respiratory virus infection. J Immunol 187:835-41
Surman, Sherri L; Brown, Scott A; Jones, Bart G et al. (2010) Clearance of HIV type 1 envelope recombinant sendai virus depends on CD4+ T cells and interferon-gamma but not B cells, CD8+ T cells, or perforin. AIDS Res Hum Retroviruses 26:783-93
Brown, Scott A; Surman, Sherri L; Sealy, Robert et al. (2010) Heterologous Prime-Boost HIV-1 Vaccination Regimens in Pre-Clinical and Clinical Trials. Viruses 2:435-467
Sealy, Robert; Zhan, Xiaoyan; Lockey, Timothy D et al. (2009) SHIV infection protects against heterologous pathogenic SHIV challenge in macaques: a gold-standard for HIV-1 vaccine development? Curr HIV Res 7:497-503
Sealy, Robert; Slobod, Karen S; Flynn, Patricia et al. (2009) Preclinical and clinical development of a multi-envelope, DNA-virus-protein (D-V-P) HIV-1 vaccine. Int Rev Immunol 28:49-68
Surman, Sherri L; Sealy, Robert; Jones, Bart G et al. (2009) HIV-1 vaccine design: harnessing diverse lymphocytes to conquer a diverse pathogen. Hum Vaccin 5:268-71
Sealy, Robert; Jones, Bart G; Surman, Sherri L et al. (2009) Short communication: The dead cell: a potent escort for HIV type 1 transinfection. AIDS Res Hum Retroviruses 25:1123-8

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