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Hurwitz: Vaccine development

We are engaged in two different vaccine studies. In each case our goal is to activate immune responses toward vaccines that mimic the structure of natural pathogens. Each of our studies represents a collaborative effort among researchers from the disciplines of immunology, virology and infectious diseases.

1) Respiratory virus vaccine development:  Respiratory syncytial virus (RSV) and human parainfluenza viruses (hPIV) are the most important causes of hospitalization for viral respiratory tract diseases in infants and young children. Unfortunately, there are currently no licensed vaccines for prevention of these infections. We are now developing Sendai virus, a natural respiratory pathogen of mice, as a Jennerian vaccine for hPIV-1, and as a vaccine backbone for the prevention of RSV and other hPIVs. Unmodified Sendai virus is currently being tested in the clinic. Thus far, the vaccine has been well-tolerated in human volunteers. Pre-clinical studies also continue and have demonstrated that Sendai virus expressing an RSV antigen can activate high-magnitude RSV-specific neutralizing B- and T-cell activities that prevent RSV infection. As clinical safety studies progress, we are also working with our collaborators to formulate a Sendai virus-based cocktail vaccine designed to prevent both hPIV and RSV infections in humans.

2) HIV-1 vaccine development: HIV-1 poses a unique challenge to researchers because of the substantial heterogeneity of envelope (Env), its outer coat protein. Immune responses elicited toward one Env will block viruses sharing that Env, but often fail to recognize or block other HIV-1 isolates. Thus, single or double-Env vaccines have not proven protective in clinical trials. At St. Jude, we acknowledge and attack HIV-1 diversity by designing Env vaccine "cocktails" that contain:

  1. Env obtained during longitudinal sampling of HIV-1 infected individuals
  2. Env from distinct subtypes worldwide, and
  3. Env that show unique binding patterns in panels of monoclonal and polyclonal antibodies.

We are currently studying the activation, maintenance and function of B-cell and T-cell responses elicited by our Env-based vaccines.