[Federal Register Volume 76, Number 160 (Thursday, August 18, 2011)]
[Notices]
[Pages 51374-51375]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-21043]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-N-0012]


Direct Discovery of HLA Associated Influenza Epitopes Isolated 
From Human Cells for Vaccine and Therapeutic Evaluation and Development 
(U01)

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of grant funds for the support of a sole source 
cooperative agreement with the University of Oklahoma Health Sciences 
Center. The goal of the FDA, Center for Drug Evaluation and Research, 
Office of Chief Scientist, is to develop technology to molecularly 
characterize peptide epitopes that are processed and presented on 
soluble HLA (human leucocyte antigen) expressed by human cells. Initial 
studies will examine and characterize influenza peptides isolated from 
several different soluble Class I HLAs produced from influenza infected 
human lung cell lines. There is a growing interest in developing 
universal vaccines for influenza by targeting conserved internal 
proteins to stimulate cross-protective CTLs (cytolytic T lymphocyte) to 
provide long-lasting immunity. It is therefore critically important to 
identify which viral epitopes are generated by antigen processing in 
influenza infected lung cells, the target cells of cell mediated immune 
response to respiratory viruses. FDA seeks a collaboration to develop 
this technology for this purpose which can then be applied to 
identifying and characterizing other HLA-presented epitopes in viral 
infections, cancer, and immune toxicities.

DATES: Important dates are as follows:
    1. The application due date is September 1, 2011.
    2. The anticipated start date is November 1, 2011.
    3. The opening date is August 18, 2011.
    4. The expiration date is November 2, 2011.

FOR FURTHER INFORMATION AND ADDITIONAL REQUIREMENTS CONTACT:
    For Programmatic questions and concerns contact: Michael Norcross, 
Center for Drug Evaluation and Research, Food and Drug Administration, 
9000 Rockville Pike, N29B, Rm. 4NN (HFD 122), Bethesda, MD 20892, 
Telephone: 301-827-0793; E-mail: [email protected].
    For Financial and Administrative questions and concerns contact: 
Gladys M. Bohler, Food and Drug Administration, Office of Acquisitions 
and Grant Services, 5630 Fisher's Lane, Rm. 1078 (HFA 500), Rockville, 
MD 20857, Telephone: 301-827-7175, E-mail: [email protected].
    For more information on this funding opportunity announcement (FOA) 
and to obtain detailed requirements, please refer to the full FOA 
located at: http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm088761.htm.

SUPPLEMENTARY INFORMATION:

I. Funding Opportunity Description

Funding Opportunity Number: RFA-FD-12-001.
Catalog of Federal Domestic Assistance Number: 93.103.

A. Background

    Knowledge on how viral and self proteins are processed and 
presented in HLA molecules is important to understand how the body 
defends itself from infection and how immune responses can lead to 
tissue toxicities. Developing technology to allow direct identification 
of epitopes bound by HLA molecules is critical to vaccine and 
therapeutic immune strategies. FDA is interested in collaborative 
research to develop and implement this technology which will be 
valuable in evaluation and review of vaccines and therapeutics. Initial 
studies will address identifying epitopes from influenza that are 
presented by different HLA alleles in infected lung cells.
    Influenza virus infection affects a significant proportion of the 
population and is associated with serious morbidity and mortality. 
Although many epitopes can be predicted by computer programs and by 
screening peripheral blood cells with panels of viral peptides from 
influenza, the peptides that are presented on the infected target cells 
in the tissues and the infiltrating T cells that recognize the HLA-
peptide complexes are the critical elements to control and recover from 
infection. The technology of directly identifying viral epitopes in HLA 
can elucidate viral targets for T cells and provide the foundation for 
new approaches for rapid development of effective vaccines. More 
effective vaccines to prevent and control influenza infections will 
have broad public health benefits by reducing morbidity and mortality 
of this infectious disease.

B. Research Objectives

    For this purpose, a direct epitope elution approach is needed to 
allow milligram quantities of HLA-peptide complexes to be purified from 
influenza infected lung cells lines that express soluble HLA. Human 
lung cell lines engineered to secrete soluble HLA from three supertypes 
(A*01, A*03, and B*27) should be infected with at least two current 
influenza strains and HLA collected during infection. HLA will be 
purified and bound peptides eluted. Influenza peptides should be 
systematically identified by mass spectrometry analysis and sequencing. 
Synthetic viral peptides can then be tested for binding to recombinant 
HLA to verify binding specificity and affinity. Influenza epitopes 
identified in this initial phase of the project can be evaluated for 
immunogenicity and antigenicity in follow up studies.
    This project will provide the regulatory science to facilitate 
development and evaluation of direct discovery of HLA presented 
epitopes. The direct epitope methodology will be applied to current 
influenza strains initially, but has the flexibility to address novel 
pandemic strains and other pathological agents.
    Goal 1: Identify virus-encoded class I HLA peptides presented 
during influenza infection of human lung cells.
    Goal 2: In vitro validation of class I HLA-presented influenza 
peptides.
    Goal 3: Develop HLA-epitope direct-discovery technology for use in 
FDA laboratories.

C. Eligibility Information

    The technology requires extensive infrastructure for growing cells, 
purifying HLA from culture supernatants, and for mass spectrometry 
analysis. Staff at the University of Oklahoma Health Sciences Center 
are leaders in this technology and have published the first reports on 
applying this method to influenza. Support of this project will allow 
the extension of the methodology to examine other HLA types. FDA 
believes this is a novel and valuable methodology that should be 
implemented at FDA. Funding this collaborative initiative will allow 
FDA to acquire the proteomic expertise, training, and tissue culture 
support to establish a laboratory in the field of immunoproteomics. The 
direct

[[Page 51375]]

identification of viral epitopes is critically important to 
understanding immune responses to infection and vaccination, and there 
are currently no comparable methods besides the classic screening of 
vast arrays of overlapping viral peptides on blood lymphocytes. Peptide 
screening methods only identify possible target epitopes, but do not 
define which epitopes are expressed in lung tissue. The technology will 
be valuable for vaccine development and evaluation, and has the 
flexibility to allow rapid analysis of novel pandemic strains for 
immunogenic epitopes. The technology can be applied to other infectious 
diseases, cancer, and immunotoxicities.

II. Award Information/Funds Available

A. Award Amount

    Only one grant award will be made in fiscal year (FY) 2012. The 
application budget is not limited, but it needs to reflect the actual 
needs of the proposed project. However, presently for FY 2012, the 
funds are available in the amount of $400,000 (total cost), and are 
subject to change based on the availability of funds.

B. Length of Support

    The maximum period is 1 year with the option of 4 more years of 
budget support depending on the availability of funds.

III. Paper Application, Registration, and Submission Information

    To submit a paper application in response to this FOA, applicants 
should first review the full announcement located at http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm088761.htm. Persons 
interested in applying for a grant may obtain an application at http://grants2.nih.gov/grants/funding/phs398/phs398.html. For all paper 
application submissions, the following steps are required:
     Step 1: Obtain a Dun and Bradstreet (DUNS) Number.
     Step 2: Register With Central Contractor Registration.
     Step 3: Register With Electronic Research Administration 
(eRA) Commons.
    Steps 1 and 2, in detail, can be found at http://www07.grants.gov/applicants/organization_registration.jsp. Step 3, in detail, can be 
found at https://commons.era.nih.gov/commons/registration/registrationInstructions.jsp. After you have followed these steps, 
submit paper applications to: Gladys Bohler, Grants Management 
Specialist (see FOR FURTHER INFORMATION CONTACT section of this 
document).

    Dated: August 9, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-21043 Filed 8-17-11; 8:45 am]
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