03-11261. Primate Model for Studying the Pathogenesis of Measles Infections and for Development of Improved Measles Vaccines; Notice of Availability of Funds

Application Deadline: June 23, 2003.

A. Authority and Catalog of Federal Domestic Assistance Number

This program is authorized under the sections 301 and 317(k)(1) of the Public Health Service Act, as amended, [42 U.S.C. 241 and 247b(k)(1)]. The Catalog of Federal Domestic Assistance number is 93.283.

B. Purpose

The Centers for Disease Control and Prevention (CDC) announces the availability of fiscal year (FY) 2003 funds for a cooperative agreement program for a Primate Model for Studying the Pathogenesis of Measles Infections and for Development of Improved Measles Vaccines. This program addresses the “Healthy People 2010” focus area of Immunization and Infectious Diseases.

The purpose of the program is to define the genetic and immunologic basis for the pathogenesis of measles virus and to use this information to develop improved vaccines for worldwide measles control efforts.

Measurable outcomes of the program will be in alignment with one or more of the following performance goals for the National Center for Infectious Diseases (NCID): Protect Americans from infectious diseases.

Any research project involving the construction and/or handling of recombinant deoxyribonucleic acid (DNA) molecules or organisms or viruses containing recombinant DNA molecules will be subject to review and approval by the CDC Institutional Biosafety Committee using the National Institutes of Health (NIH) Guidelines: http://www4.od.nih.gov/​oba/​rac/​guidelines/​guidelines.html

C. Eligible Applicants

Applications may be submitted by public and private nonprofit organizations and by governments and their agencies, this includes:

• Universities
• Colleges
• Technical schools
• Research Institutions
• Hospitals
• Community-based organizations
• Faith-based organizations
• Federally recognized Indian tribal governments
• Indian Tribes
• Indian tribal organizations
• State and local governments or their bona fide agents (this includes the District of Columbia, the Commonwealth of Puerto Rico, the Virgin Islands, the Commonwealth of the Northern Mariana Islands, American Samoa, Guam, the Federated States of Micronesia, the Republic of the Marshall Islands, and the Republic of Palau)
• Political subdivisions of States (in consultation with States)

Note:

Title 2 of the United States Code section 1611 states that an organization described in section 501(c)(4) of the Internal Revenue Code that engages in lobbying activities is not eligible to receive Federal funds constituting an award, grant or loan.

D. Funding

Availability of Funds

Approximately $200,000 is available in FY 2003 to fund one award. It is expected that the award will begin on or about September 15, 2003, and will be made for a 12-month budget period within a project period of up to 3 years. The funding estimate may change.

Continuation awards within an approved project period will be made on the basis of satisfactory progress as evidenced by required reports and the availability of funds.

Recipient Financial Participation

Matching funds are not required for this program.

Funding Preferences

Applications for new studies are encouraged, however, funding preference may be given to the competing continuation application over applications for programs not already receiving support under the existing program. The current awardee has implemented vaccine research that requires continued support to become fully developed and to realize the benefits of an improved vaccine.

E. Program Requirements

In conducting activities to achieve the purpose of this program, the recipient will be responsible for the activities listed in 1. Recipient Activities, and CDC will be responsible for the activities listed in 2. CDC Activities.

1. Recipient Activities

(a) Develop a study design to accomplish the following research goals:

(1) Use the rhesus macaque as a primate model for measles infections. These studies which produce disease in rhesus that closely resembles measles in humans will describe the pathogenesis of measles in the primate model.

(2) Characterize the immune response to natural measles disease and measles vaccination. Studies should attempt to measure differences between the immune response in animals receiving measles vaccines to those experiencing infection with a virulent strain. Efforts should be aimed at providing a complete description of the humoral, and especially, the cellular immune responses. These studies should include and broaden our understanding of cell mediated immunity by mapping CD4 and CD8 T-cell reactive epitopes on measles antigens and by measuring the cytokine/chemokine responses following infection or vaccination.

(3) Develop improved measles vaccines. Research efforts should be directed at developing, testing and optimizing novel vaccine formulations that could be used to stimulate an immune response in the presence of maternal antibody. Such vaccines would be used to protect newborn humans from measles infection or disease during their first year of life. In addition, subunit or DNA vaccines that could be used to stimulate or boost immunity in immunocompromized individuals should also be considered. Using recombinant measles viruses as a vector to present other antigens should also be considered.

(4) Conduct studies to evaluate the safety and efficacy of standard measles vaccines given by alternate routes. In particular, studies to evaluate the safety and efficacy of measles vaccines given as aerosols or dry powders via the intranasal route should be conducted in normal and immunosuppressed animals. Evaluation of immune response to individual measles virus antigens.

(5) Conduct studies to determine the genetic basis for virulence of measles virus in the rhesus macaque. Studies should include experimental infections with recombinant measles viruses that have defined genetic characteristics. Another important goal will be the maintenance and genetic characterization of viral stocks which can reliably produce disease in rhesus by the intranasal route. Conduct detailed analysis of these stocks to help understand the genetic basis for the pathogenesis of measles virus.

(b) Perform all inoculations of research animals. Maintain records of clinical observations and obtain samples for laboratory analysis.

(c) Perform specialized tests on specimens obtained from study animals and coordinate shipment of specimens to CDC for additional testing.

(d) Provide routine veterinary care, housing and other support for rhesus macaques to be used in experiments. Comply fully with PHS policies regarding research on animal subjects.

(e) Maintain sufficient numbers of rhesus macaques so that experiments can be completed in a timely manner.

(f) Develop experimental measles vaccines and evaluate them in the animal model.

(g) Analyze data and manuscripts describing results of research investigations.

2. CDC Activities

(a) Collaborate on the design and conduct of the research.

(b) Collaborate in the development of various preparations of measles virus antigens, recombinant viruses, rescued viruses or complementary DNA (cDNA) clones for use as experimental vaccines.

(c) Provide Direct Assistance for specialty reagents, such as monoclonal and polyclonal antiserum, and PCR primers as needed.

(d) Conduct specialized analysis of samples obtained from test animals and assist with genetic characterization of viruses used in the study.

(e) Collaborate in data analysis, manuscript preparation and presentation.

F. Content

Letter of Intent (LOI)

An LOI is optional for this program. The Program Announcement title and number must appear in the LOI. The narrative should be no more than two pages, single-spaced, printed on one side, with one-inch margins, and unreduced 12-point font. Your letter of intent will be used to enable CDC to determine the level of interest in the announcement and should include the following information, a brief description of the proposed study, the business address of the organization, and the name and phone number of the Principal Investigator.

Applications

The Program Announcement title and number must appear in the application. Use the information in the Program Requirements, Other Requirements, and Evaluation Criteria sections to develop the application content. Your application will be evaluated on the criteria listed, so it is important to follow them in laying out your program plan. The narrative should be no more than ten pages, double-spaced, printed on one side, with one-inch margins, and unreduced 12-point font.

The narrative should consist of Background and Need, Capacity, Objectives and Technical Approach, Measures of Effectiveness, Budget, and Animal Subjects.

G. Submission and Deadline

Letter of Intent (LOI) Submission

On or before May 22, 2003, submit the LOI to the Grants Management Specialist identified in the “Where to Obtain Additional Information” section of this announcement.

Application Forms

Submit the signed original and two copies of PHS 398 (OMB Number 0920-0001). Adhere to the instructions on the Errata Instruction Sheet (posted on the CDC website) for PHS 398. Forms are available at the following Internet address: www.cdc.gov/​od/​pgo/​forminfo.htm

If you do not have access to the Internet, or if you have difficulty accessing the forms on-line, you may contact the CDC Procurement and Grants Office Technical Information Management Section (PGO-TIM) at: 770-488-2700. Application forms can be mailed to you.

Submission Date, Time, and Address

The application must be received by 4 p.m. Eastern Time June 23, 2003. Submit the application to: Technical Information Management—PA03068, CDC Procurement and Grants Office, 2920 Brandywine Road, Atlanta, GA 30341-4146. Applications may not be submitted electronically.

CDC Acknowledgment of Application Receipt

A postcard will be mailed by PGO-TIM, notifying you that CDC has received your application.

Deadline

Applications shall be considered as meeting the deadline if they are received before 4 p.m. Eastern Time on the deadline date. Any applicant who sends their application by the United States Postal Service or commercial delivery services must ensure that the carrier will be able to guarantee delivery of the application by the closing date and time. If an application is received after closing due to (1) carrier error, when the carrier accepted the package with a guarantee for delivery by the closing date and time, or (2)significant weather delays or natural disasters, CDC will upon receipt of proper documentation, consider the application as having been received by the deadline.

Any application that does not meet the above criteria will not be eligible for competition, and will be discarded. The applicant will be notified of their failure to meet the submission requirements.

H. Evaluation Criteria

Applicants are required to provide Measures of Effectiveness that will demonstrate the accomplishment of the various identified objectives of the [grant or cooperative agreement]. Measures of Effectiveness must relate to the performance goals stated in the purpose section of this announcement. Measures must be objective and quantitative and must measure the intended outcome. These measures of effectiveness must be submitted with the application and will be an element of evaluation.

An independent review group appointed by CDC will evaluate each application against the following criteria:

1. Capacity (45 total points). (a) Extent to which applicant demonstrates experience with viral pathogenesis and immunology in rhesus macaques or other primate system. Extent to which the applicant can demonstrate previous or ongoing experience with measles infections of primates. Extent to which the applicant can produce a measles infection that is similar to measles infections in humans in rhesus macaques following intranasal inoculation. (30 points)

(b) Extent to which applicant documents that professional personnel involved in the project are qualified and have past experience and achievements in research related to that proposed in this cooperative agreement as evidenced by curriculum vitae, publications, etc. Extent to which the applicant demonstrates experience with virology, particularly the virology of measles virus. (10 points)

(c) Extent to which applicant describes adequate resources and facilities for conducting the project. Extent to which facilities for the safe handling of infectious agents are available. (5 points)

2. Objectives and Technical Approach (40 total points). (a) Extent to which the plan clearly describes applicant's technical approach/methods for conducting the proposed studies. Extent to which applicant describes specific study protocols or plans for the development of study protocols that are appropriate for achieving project objectives. (20 points)

(b) Extent to which applicant provides a detailed plan for evaluating study results and for evaluating progress towards achieving project objectives. (15 points)

(c) Extent to which applicant describes objectives of the proposed project which are consistent with the purpose and program requirements of this cooperative agreement and which are measurable and time-phased. (5 points)

3. Background and Need (10 points). Extent to which applicant demonstrates a clear understanding of the purpose and objectives of this proposed cooperative agreement.

4. Measures of Effectiveness (5 points). Does the applicant provide Measures of Effectiveness that will demonstrate the accomplishment of the various identified objectives of the grant? Are the measures objective/quantitative and do they adequately measure the intended outcome?

5. Budget (Not Scored). Extent to which the proposed budget is reasonable, clearly justifiable, and consistent with the intended use of cooperative agreement funds.

6. Animal Subjects (Not Scored). Extent to which the application adequately addresses the requirements of Public Health Policy on Humane Care and Use of Laboratory Animals.

I. Other Requirements

Technical Reporting Requirements

Provide CDC with original plus two copies of:

1. Interim progress report, no less than 90 days before the end of the budget period. The progress report will serve as your non-competing continuation application, and must contain the following elements:

a. Current Budget Period Activity Objectives.

b. Current Budget Period Financial Progress.

c. New Budget Period Program Proposed Activity Objectives.

d. Detailed Line-Item Budget and Justification.

e. Additional Requested Information.

2. Financial status report, no more than 90 days after the end of the budget period.

3. Final financial and performance reports, no more than 90 days after the end of the project period.

Send all reports to the Grants Management Specialist identified in the “Where to Obtain Additional Information” section of this announcement.

Additional Requirements

The following additional requirements are applicable to this program. For a complete description of each, see Attachment I of the program announcement, as posted on the CDC website.

AR-3—Animal Subjects Requirements

AR-7—Executive Order 12372

AR-10—Smoke Free Work Place Requirements

AR-11—Healthy People 2010

AR-12—Lobbying Restrictions

AR-15—Proof of Non-Profit Status

AR-22—Research Integrity

J. Where To Obtain Additional Information

This and other CDC announcements, the necessary applications, and associated forms can be found on the CDC web site, Internet address: http://www.cdc.gov Click on “Funding” then “Grants and Cooperative Agreements.”

For general questions about this announcement, contact: Technical Information Management, CDC Procurement and Grants Office, 2920 Brandywine Road, Atlanta, GA 30341-4146, Telephone: [phone].

For business management and budget assistance, contact: Jeff Napier, Grants Management Specialist, Procurement and Grants Office, Centers for Disease Control and Prevention, 2920 Brandywine Road, Atlanta, GA 30341-4146, Telephone: [phone], E-mail Address: [e-mail].

For program technical assistance, contact: Paul A. Rota, Ph.D., Supervisory Microbiologist, National Center for Infectious Diseases, Centers for Disease Control and Prevention, MS-C-22, 1600 Clifton Road, NE., Atlanta, GA 30333, Telephone: [phone], E-mail: [e-mail].

Dated: May 1, 2003.

Edward Schultz,

Acting Director, Procurement and Grants Office, Centers for Disease Control and Prevention.