Abstract

The long term objective of this project is to develop a vaccine to protect humans from antigenically different forms of HIV-1 found in nature. Such protection will require elicitation of immune responses against diverse HIV- 1 envelop proteins. We submit that multiple HIV-1 envelope proteins must be presented in a vaccine to induce immunological memory against the range of HIV-1 variants. We further proposed that the magnitude of diverse responses may be optimized by utilization of more than one vaccine delivery system. Our pre-clinical studies evaluation a three-tired vaccine delivery system with (i) recombinant DNA vaccine followed by (ii) recombinant vaccinia virus vaccine followed by (iii) purified protein vaccine (D-V-P) demonstrate high levels of HIV-1 neutralizing antibodies in mice. The goal of this project is to translate this vaccine strategy to human application. A multi-envelope recombinant vaccinia virus vaccine (PolyEnv1) is currently in clinical trial (Project 4). Accordingly, in this project we will prepare DNA and purified proteins fro use in humans. The first two aims of this project describe the design and production of clinical grade material. While technically driven these two aims are critical for the conduct of small scale human trials (Project 4).
The third aim tests the hypothesis that these aims are critical for the conduct of small scale human trials (Project).
The third aim tests the hypothesis that our 3-tiered, multi- envelope vaccine strategy can protect non-human primates from heterologous virus. The implementation of this aim is critical for clinical advanced of the vaccine approach.
Specific aims developed in this project are:
Aim 1 : To prepare a multi-envelope DNA vaccine that is safe, immunogenic and suitable for use in humans.
Aim 2 : To prepare a multi-envelope protein vaccine that is safe, immunogenic and suitable for use in humans.
Aim 3 : To determine whether a three-tiered multi-envelope vaccine protects non-human primates from heterologous virus challenge.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI045142-03
Application #
6455342
Study Section
Project Start
2001-05-01
Project End
2002-04-30
Budget Start
Budget End
Support Year
3
Fiscal Year
2001
Total Cost
Indirect Cost

  Institution

Name
St. Jude Children's Research Hospital
Department
Type
DUNS #
067717892
City
Memphis
State
TN
Country
United States
Zip Code
38105

  Publications

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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