[Federal Register Volume 67, Number 45 (Thursday, March 7, 2002)]
[Notices]
[Pages 10420-10421]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-5504]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


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.

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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: 301/
496-2644, Fax: 301/402-7123; Electronic mail: [email protected].

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

[[Page 10421]]

requisite vaccine safety, immunogenicity, and efficacy studies in 
humans.

    Dated: February 28, 2002.
Michael R. Mowatt,
Director, Office of Technology Development, NIAID.
[FR Doc. 02-5504 Filed 3-6-02; 8:45 am]
BILLING CODE 4140-01-P