02-5504. Opportunity for a Cooperative Research and Development Agreement (CRADA) To Develop Live Attenuated Dengue Viruses for Use as Vaccines in Humans

AGENCY:

National Institutes of Health, HHS.

ACTION:

Notice.

SUMMARY:

The National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) is seeking Capability Statements from parties interested in entering into a Cooperative Research and Development Agreement (CRADA) on a project to develop live attenuated dengue viruses for use as vaccines to prevent dengue hemorrhagic fever and dengue shock syndrome in humans. This project is part of ongoing vaccine development activities in the Laboratory of Infectious Diseases (LID), Division of Intramural Research, NIAID.

DATES:

Only written CRADA Capability Statements received by the NIAID on or before April 18, 2002, will be considered.

ADDRESSES:

Capability Statements should be submitted to Dr. Michael R. Mowatt, Office of Technology Development, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 31 Center Drive MSC 2137, Building 31, Room 3B62, Bethesda, MD 20892-2137; Tel: [phone], Fax: [phone]; Electronic mail: [e-mail].

SUPPLEMENTARY INFORMATION:

The CRADA will employ attenuated dengue virus strains (types 1 through 4) developed in LID using recombinant DNA methodologies to (1) identify and characterize the mutations responsible for attenuation, (2) engineer viral strains suitably attenuated for use as human vaccines, and (3) evaluate the attenuated viruses as live vaccines in animals, including rhesus monkeys, and humans. The Public Health Service (PHS) has filed patent applications both in the U.S. and internationally related to these technologies.

The LID has extensive experience in evaluating the safety, immunogenicity and efficacy of various human viral pathogens and vaccines thereof both in experimental animals and human volunteers. The LID has identified two approaches to produce attenuated dengue virus vaccine candidates each incorporating a stable, clinically tested deletion mutation capable of attenuating dengue viruses for humans. In addition, a large set of additional attenuating mutations have been identified that will be available to further attenuate vaccine candidates that prove to be incompletely attenuated in human trials. The Collaborator in this endeavor is expected to commit several scientists off-site to support the activities defined by the CRADA Research Plan. These scientists, in collaboration with investigators in the LID, would coordinate the production and release testing of the candidate vaccines, generate monoclonal antibodies or other antibodies needed for production and characterization of clinical lots, and use molecular virologic techniques to generate attenuating mutations suitable for use in live vaccine candidates. The LID and Collaborator will identify the best candidate dengue virus attenuated derivatives for each of the four dengue virus serotypes to formulate a tetravalent vaccine. In addition, it is expected that the Collaborator will provide funds to supplement LID's research budget for the project and would make a major funding commitment to support the safety, immunogenicity and efficacy studies for candidate vaccines developed under the CRADA.

The capability statement must address, with specificity and providing appropriate examples, each of the following selection criteria: (1) The technical expertise of the Collaborator's Principal Investigator and laboratory group in molecular virology; (2) The number of personnel that the Collaborator plans to assign to this project; (3) Ability of Collaborator to manufacture experimental vaccine lots for parenteral administration under Good Manufacturing Practices (GMP) conditions and the number of lots that could be produced annually, (4) Access to a qualified bank of cells for vaccine manufacture, specifically Vero cells or DBS FRhL-2 cells, (5) Capability to manage regulatory affairs attendant to licensure by FDA and international regulatory bodies, and (6) Ability to provide adequate and sustained funding to support pre-clinical development at NIH and at collaborator's site and for the requisite vaccine safety, immunogenicity, and efficacy studies in humans.

Dated: February 28, 2002.

Michael R. Mowatt,

Director, Office of Technology Development, NIAID.