SPECIAL NOTICE
A -- Development of HIV candidate vaccines that elicit broadly cross-reactive HIV neutralizing antibodies
- Notice Date
- 12/10/2002
- Notice Type
- Special Notice
- Contracting Office
- Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Bldg 427 Room 12, Frederick, MD, 21702
- ZIP Code
- 21702
- Archive Date
- 1/30/2003
- Description
- The National Cancer Institute seeks partners to participate in a Cooperative Research and Development Agreement (CRADA) to develop the following technology. This technology encompasses tethered HIV envelope glycoprotein (Env) constructs where gp120 and the ectodomain of gp41 are joined by flexible linkers. Tethered Envs with long linkers (longer than 15 aa but shorter than 30 aa) were stable and recognized by conformationally dependent anti-gp120 and anti-gp41 monoclonal antibodies (mAbs). Surprisingly, these proteins potently inhibited membrane fusion mediated by R5, X4 and R5X4 Envs. Compared to uncleaved soluble Env tethered Envs which exhibited increased binding to anti-gp41 cluster II mAbs but not to cluster I mAbs. Cluster II mAbs but not cluster I, IV or V mAbs reversed their inhibitory effect, suggesting the mechanism of inhibition might be due to exposed conserved gp41 structures. These findings suggest the existence of conserved gp41 structures that are important for HIV-1 entry and can be stably exposed in the native environment of the Env even in the absence of receptor-mediated activation. Thus tethered Envs with long linkers may be important for the development of novel vaccine immunogens. Preliminary experiments with DNA immunization of mice suggest that tethered Envs elicit antibodies that neutralize heterologous isolates about 10-fold better than sera from mice immunized with gp120. NCI is seeking collaborators to further develop and characterize the tethered Envs as candidate vaccines and eventually perform clinical trials. The NCI has a variety of assays for in vitro evaluation of the sera, and can engineer different modifications of the tethered Envs for enhancement of the their immunogenicity. Potential Areas of Application: ? HIV preventive vaccines ? Therapeutic HIV vaccines ? Research reagents Main Advantages of the Technology: ? Novel concept for elicitation of broadly cross-reactive HIV neutralizing antibodies ? Can be used as DNA vaccines that are more stable State of Development: ? Lead molecules developed and characterized in vitro, and to some extent in vivo Further R&D Required: ? Preclinical development ? Animal studies ? Preclinical and clinical analyses The role of the NCI in the CRADA may include, but not be limited to: 1. Providing intellectual, scientific, and technical expertise and experience in developing broadly neutralizing antibodies. 2. Providing the CRADA collaborator with information and data relating to the methods developed to assess the activity ofa variety of assays for validating the sera. 3. Planning research studies and interpreting research results. 4. Develop additional validation methods for selected immunogens in preclinical, diagnostic and clinical settings. 5. Publish research results. The role of the CRADA Collaborator may include, but not be limited to: 1. Providing significant intellectual, scientific, and technical expertise or experience in vaccine development. 2. Providing technical and/or financial support to facilitate scientific goals and for further design of applications of the technology outlined in the agreement. 3. Publish research results. Terms/Licensing Potential/Patent Status: ? Typical term of the CRADA will be five (5) years ? No funding from the Government is available ? Option to an exclusive license to the collaborator for CRADA Subject Inventions ? Non-exclusive license option available for background rights ? One patent application filed (March 2002) Selection Criteria: The NCI seeks a collaborator with experience in conducting preclinical studies and early phase clinical trials with vaccines. The collaborator should have demonstrated capability to produce candidate vaccines in quantities and conduct clinical trials. The collaborator should also have demonstrated capability to scale up production of candidate vaccines. ? Appropriate Technical/Scientific Expertise ? Solid Company Reputation in the field ? Sufficient Physical Resources References: Chow, Y.-H., Wei, O.L., Phogat, S., Sidorov, I.A., Fouts, T.R., Broder, C.C., Dimitrov, D.S. Conserved structures exposed in HIV-1 envelope glycoproteins stabilized by flexible linkers as potent entry inhibitors and potential immunogens. Biochemistry, 41(22): 6256-6262, 2002 - describes the development and characterization of the tethered Envs Biragyn, A., Belyakov, I.M., Chow, Y.H., Dimitrov, D.S., Berzofsky, J.A., Kwak, L.W. DNA vaccines encoding HIV-1 gp120 fusions with proinflammatory chemo-attractants induce systemic and mucosal immune responses. Blood, 100(4):1153-1159, 2002 - describes preliminary data from mice immunization with tethered Envs fused with chemokines. Also see: http://www-lecb.ncifcrf.gov/~dimitrov/dimitrov.html Submission Dates: ? Interested parties are asked to submit a written statement of interests in this CRADA opportunity by Wednesday, January 15, 2003. Contact Information: Dr. Charmaine Richman Technology Transfer Specialist Technology Transfer Branch National Cancer Institute 1003 West Seventh Street Suite 500 Frederick, Maryland 21701 telephone: 301-846-5465 fax 301-846-6820 e-mail: richmanc@mail.nih.gov
- Web Link
-
Link to FedBizOpps document.
(http://www.eps.gov/spg/HHS/NIH/FCRF/Reference-Number-CR01/listing.html)
- Record
- SN00221167-F 20021212/021211053303 (fbodaily.com)
- Source
-
FedBizOpps.gov Link to This Notice
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