St. Jude Children's Research Hospital (SJCRH) initiated an HIV-1 vaccine program five years ago with the conviction that his complex issue would be most effectively addressed through a coordinated, multi-disciplinary approach; the program thus currently involves investigators from SJCRH departments of Immunology , Virology, Infectious Diseases and Structural Biology. The central problem in developing an effective HIV-1 vaccine lies in the antigenic diversity of the virus. The SJCRH HIV-1 vaccine program is unique in explicitly acknowledging this antigenic complexity, by matching the diversity of the pathogen with a diversity of vaccine structures. Thus far, work within the program has resulted in the initiation of an FDA-approved, phase I clinical trial of PolyEnv1, the first HIV vaccine to encompass more than one or two HIV envelope protein structures. The ongoing clinical trial with PolyEnv1 has employed an attenuated live virus vehicle to deliver the vaccine. Preliminary data indicate that modification of the vaccination regime to deliver the cocktail of envelope protein structures represented in PolyEnv1 in a sequential combination of three different immunogenic forms (DNA, attenuated virus and native protein) may result in the generation of neutralizing antibodies at a much increased titer.
Specific Aims i n Projects 1 (P. Doherty) and 2 (R. Webster) use mouse models to explore the nature of the immune response to combinations of immunogenic forms, to optimize vaccination schemes and to determine the relationship between immunogen complexity and vaccine efficiency. Project 3 (J. Hurwitz) implements the findings of Projects 1 and 2 in a primate (macaques) model of vaccination against immunodeficiency virus infection, as well as developing optimal vaccine manufacturing schemes. Project 4 (K. Slobod) builds on these studies, initiating clinical trials of the safety and effectiveness of vaccines comprised of combinations of immunogenic envelopes.
|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|
|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|
|Hurwitz, Julia L (2011) Respiratory syncytial virus vaccine development. Expert Rev Vaccines 10:1415-33|
|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|
|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|
|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|
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