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Barouch: Replicating Adenovirus Vectors

OVERVIEW

The consortia led by Dr. Dan Barouch at the Beth Israel Deaconess Medical Center will address the hypothesis that replicating adenovirus (Ad) vectors can induce potent HIV-specific mucosal immune responses as well as fundamentally different qualities of immune responses when compared with non-replicating Ad vectors. The impact of vector replication on the magnitude, durability, and quality of vaccine-elicited HIV-specific immune responses as compared to non-replicating Ad vectors will be evaluated in Phase 1 studies in healthy volunteers. The replicating Ad vectors will include the “mosaic” HIV-1 Env antigen, which is an in silico recombined antigen sequence aimed at optimizing immunologic coverage of global virus diversity.

The work done by the consortia will lead to the development of an HIV vaccine using a replicating adenovirus vector based on either serotype 26 or 35 and expressing the HIV mosaic antigens. Ad35 and Ad26 are subtypes of adenovirus that are less prevalent in human populations and biologically substantially different than Ad5. These serotypes therefore may offer important advantages over Ad5.

Dr Barouch has extensive experience with preclinical-to-clinical development of novel HIV-1 vaccines, including the recent successful development of non-replicating Ad26 and Ad35 vectors into Phase 1 clinical trials. This program builds upon the productive ongoing collaborations among the investigators within the consortia.

RESEARCH OBJECTIVES

  1. Perform preclinical evaluation of replicating simian Ad vectors to determine their immunogenicity and efficacy in the non-human primate (NHP) challenge model.
  2. Complete GMP manufacturing and release of Ad35 or Ad26 mosiac HIV vaccine for use in Phase 1 studies.
  3. Complete a toxicology study of the Ad mosaic HIV vaccine and obtain regulatory clearance to initiate a Phase 1 clinical study.
  4. Conduct a Phase 1 study to evaluate the immunogenicity of replicating and non-replicating Ad mosaic HIV vectors in healthy volunteers.

PROGRESS

Replicating and nonreplicating simian adenovirus vectors have been constructed for preclinical studies.  Clinical-grade pre-master virus seed stocks of replicating Ad26 expressing mosaic HIV-1 Env have been produced, and process development and scale-up activities are in progress.

 

Grant at a Glance

Principal Investigator

Dan H. Barouch, M.D., Ph.D.

Grantee Institution

Beth Israel Deaconess Medical Center, Boston, USA

Project Title

Replicating Adenovirus Mosaic HIV-1 Vaccine

Grant Award

$11.9 million over 4 years, awarded October 2011

Collaborating Institutions

  • Batavia Bioservices
  • Brigham and Women's Hospital
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