ESTABLISHMENT OF SPECIFIC PATHOGEN FREE RHESUS MACAQUE COLONIES

Release Date:  February 10, 2000
 
RFA:  RR-00-004  
 
National Center for Research Resources
 
Letter of Intent Receipt Date: March 15, 2000
Application Receipt Date: April 26, 2000
 
PURPOSE
 
Increased numbers of rhesus macaques of Indian ancestry are needed for 
AIDS vaccine and pathogenesis studies.  The purpose of this Request for 
Applications (RFA) is to solicit proposals from prospective grantees 
who can breed rhesus macaques that are Specific Pathogen Free (SPF) and 
provide them to NIH grantees for AIDS-related research.  The term SPF 
in the context of this solicitation is defined as animals free 
(antibody negative) of herpes B virus, simian immundeficiency virus 
(SIV), Type D simian retrovirus (SRV), and simian T-lymphotropic virus 
(STLV-1).  The presence of the retroviral infections makes the infected 
animals unsuitable for AIDS-related research projects.  Thus, for the 
purposes of testing potential AIDS vaccines as well as studies 
regarding the pathogenesis of AIDS, investigators must have animals 
free of viruses that might compromise their research findings.  
Although the herpes B virus does not appear to compromise AIDS-related 
investigations, the potential health risks for personnel dictates that 
the breeding colonies must be free of this virus as well.  Providing 
such animals for NIH grantees to do AIDS-related research is the 
topmost priority of this RFA.
 
HEALTHY PEOPLE 2010
 
The Public Health Service (PHS) is committed to achieving the health 
promotion and disease prevention objectives of "Healthy People 2010," a 
PHS-led national activity for setting priority areas.  This RFA, 
 Establishment of Specific Pathogen Free Rhesus Macaque Colonies , is 
related to several priority areas, including AIDS, cancer, heart 
disease and stroke, diabetes and chronic disability conditions, 
maternal and infant health, and others.  Potential applicants may 
obtain a copy of "Healthy People 2010" at 
http://odphp.osophs.dhhs.gov/pubs/hp2000.
 
ELIGIBILITY REQUIREMENTS
 
Applications may be submitted by domestic, for-profit and non-profit 
organizations, public and private, such as universities, colleges, 
hospitals, laboratories, units of State and local governments, and 
eligible agencies of the Federal government. Foreign institutions are 
not eligible.  Racial/ethnic minority individuals, women, and persons 
with disabilities are encouraged to apply as Principal Investigators.

MECHANISM OF SUPPORT
 
This RFA will use an  Animal Model and Animal and Biological Material 
Resource  Cooperative Agreement(U42)Grant mechanism.  Responsibility 
for the planning, direction, and execution of the proposed project will 
be solely that of the applicant.  The total project period for an 
application submitted in response to this RFA may not exceed 5 years.   
 
Because the nature and scope of the research proposed in response
to this RFA may vary, it is anticipated that the size of an award
will vary also.
 
This RFA is a one-time solicitation.  Future unsolicited competing
continuation applications will compete with all investigator-
initiated applications and be reviewed according to the customary
peer review procedures.   

The administrative and funding instrument to be used for this program 
will be an  Animal (Mammalian and Non-Mammalian) Model, and Animal and 
Biological Materials Resource Cooperative Agreement (U42), an 
 assistance  mechanism (rather than an  acquisition  mechanism), in 
which substantial NCRR scientific and/or programmatic involvement with 
the awardees is anticipated during the performance of the activity.  
Under the cooperative agreement, the NCRR’s purpose is to support 
and/or stimulate the recipient’s activity by involvement in, and 
otherwise working jointly with the award recipient in a partnership 
role, but it is not to assume direction, primary responsibility, or a 
dominant role in the activity.  Details of the responsibilities, 
relationships and governance of the activities to be funded under 
cooperative agreements are discussed later in this document.
 
FUNDS AVAILABLE
 
The NCRR anticipates making awards for three or four SPF colonies for 
project periods of up to five years.  Approximately $3.0 million total 
costs is expected to be set aside for funding these activities in the 
initial year.  The number of awards and the level of support will 
depend upon receipt of a sufficient number of applications of high 
scientific merit.  Although this program is provided for in the 
financial plans of the NCRR, awards pursuant to this RFA are contingent 
upon the availability of funds for this purpose in fiscal year 2000.  
The anticipated award date is September 29, 2000.   

RESEARCH OBJECTIVES
 
Background
 
In response to the critical need for providing rhesus macaques with 
specific qualities, the NCRR will establish breeding colonies through a 
Cooperative Agreement Grant mechanism.  The rhesus macaques must be of 
Asian Indian desent.  In addition, these animals must be free of the 
following retroviruses: simian immunodeficiency virus (SIV), Type D 
simian retrovirus (SRV), and simian T-lymphoyte virus (STLV-1).  
Because of prospective health risks to personnel, a further requirement 
is for these animals to be free of Herpesvirus simiae (herpes B virus).   

It is also recognized that there is a special need for Major 
Histocompatability (MHC) defined rhesus macaques for certain types of 
AIDS-related research.  A major component of the evaluation of AIDS 
vaccines in non-human primates, and in humans, is the measurement of 
virus-specific T-cell immune responses.  The majority of immunogenic 
Cytotoxic T Lymphocytes (CTL) bind to MHC class I molecules.  Mamu-A 
*01 is an example of one MHC class I haplotype that is important in 
controlling viral replication.  Thus, although the screening of such 
animals is not within the purview of this RFA, special consideration 
will be given to those colonies whose programs are targeted toward 
selected pedigree breeding for these MHC type I haplotypes.  A specific 
example is if collaborative arrangements have been established for the 
screening of MHC-1 haplotype, such an arrangement would facilitate the 
genetic management of the colonies to provide genetically-defined 
animals for AIDS research.  Such animals could be invaluable for the 
AIDS research community.

SPECIAL REQUIREMENTS

The cooperative agreements (U42s) will require cooperation between the 
NCRR representative (NCRR Program Administrator) and the Principle 
Investigators (PIs) of the individual projects in order to assure 
smooth interactions among cooperating organizations.  The NCRR Program 
Administrator will assist in coordinating the activities of the 
awardees and in facilitating exchange of animals.

TERMS AND CONDITIONS OF AWARD

The following terms and conditions will be incorporated into the U42 
award statement, and will be provided to the PI and the awardee 
institutional official at the time of award.

These special Terms of Award are in addition to, and not in lieu of, 
otherwise applicable OMB administrative guidelines, HHS Grant 
Administration Regulations at 45 CFR Parts 74 and 92, and other HHS, 
PHS, and NIH Grant Administration policy statements.  (Part 92 applies 
when state and local governments are eligible to apply as a  domestic 
organization. )

1. COLLABORATIVE RESPONSIBILITIES

Coordinating Committee (CC)

The NCRR Program Administrator and awardees are responsible for forming 
a CC as defined below.  The CC is responsible for implementation 
oversight and coordination in the establishment and operation of the 
SPF colonies as proposed in the individual applications of the 
awardees.  They will develop uniform procedures for quality control in 
animal husbandry and in the maintenance of the animal facilities.  The 
CC will be responsible for the oversight to ensure standardization of 
the viral screening assays.  The CC will continually review and monitor 
the operating procedures proposed by individual awardee organizations 
in order to ensure that they are compatible with the overall goals of 
the RFA.

The CC will initially consist of the PI of each SPF colony and NCRR 
Program Administrator.  Additional members can be added by action of 
the CC.  The structure of the CC should be established at the first 
meeting as noted below.  The Chair of the CC will be responsible for 
coordinating the Committee activities, for preparing meeting agendas, 
and for scheduling and chairing meetings.  The NCRR Program 
Administrator attends and participates in all meetings of the CC and 
should be informed of any major interactions.  The CC must prepare an 
annual progress report which will include individual reports from each 
awardee.  Each awardee is responsible for timely preparation of this 
report.

At its initial meeting, the Committee will elect a chairperson (who may 
not be the NCRR Program Administrator).  The CC will determine whether 
additional CC representation is required.

The CC will meet three times in the first year to map strategies, to 
develop operating procedures and to evaluate progress.  The initial 
meeting will be held as soon as possible after funding.  Two additional 
meetings will be held during the first year of operation and there will 
be at least two meetings per year thereafter.  Meetings may be held at 
any of the participating organizations or at another convenient 
location.  These meetings are aimed at coordinating the activities of 
the participating facilities, establishing new policies and priorities, 
reviewing progress and providing oversight for the distribution of SPF 
animals to NIH grantees.  The NCRR Program Administrator will 
participate in the discussions at these meetings.

The NCRR Program Administrator, as a member of the CC, will assure that 
operating policies are acceptable to the NCRR.  An arbitration system, 
as detailed below, will be available to resolve disagreements between 
awardees and NCRR staff.

2. AWARDEE RIGHTS AND RESPONSIBILITIES

o  Awardees will have primary and lead responsibilities for the project 
as a whole, including selection and maintenance of rhesus macaques, 
husbandry, microbiological and genetic monitoring, data quality control 
and reporting to the CC, any research to enhance the resource, 
preparation of publications, as well as collaboration with the other 
awardees with assistance from the NCRR Program Administrator.

o  Awardees must comply with the operating policies and procedures 
developed by the CC.

o  Awardees will retain custody of, and have primary rights to, the 
data developed under these awards, subject to Government rights of 
access consistent with current HHS, PHS, and NIH policies.  
Investigators conducting biomedical research frequently develop unique 
research resources.  The policy of the PHS is to make available to the 
public the results and accomplishments of the activities that it funds.  
All awardees must adhere to PHS policy for the distribution of unique 
research resources produced with PHS funding and is available at the 
following internet address:  
http://grants.nih.gov/grants/policy/nihgps/policy_stmt.htm

3. NCRR PROGRAM ADMINISTRATOR RESPONSIBILITIES

o  The NCRR Program Administrator will coordinate and facilitate the 
programs supported by these cooperative agreements, will attend and 
participate as a voting member in all meetings of the CC and SPF Colony 
Directors, and will provide liaison between them and the NCRR.
o  The NCRR Program Administrator will ensure that there is effective 
communication between the CC and NCRR.

o  The NCRR Program Administrator will assist the CC in developing and 
drafting operating policies and procedures for dealing with recurring 
situations that require coordinated action, e.g., standardized genetic 
and microbiological monitoring.

o  The NCRR Program Administrator in conjunction with CC activities 
will play a significant role in ensuring the equitable distribution of 
SPF animals to NIH grantees.

o  The NCRR Program Administrator may review the operations of 
individual U42 grants for compliance with the operating policies 
developed by the CC and may recommend withholding of support, 
suspension, or termination of an award for lack of progress or failure 
to adhere to policies established by the CC.

4. ARBITRATION PROCEDURES

An arbitration panel of external consultants will be created as needed 
to resolve any irreconcilable differences of opinion related to 
scientific/programmatic matters between the NCRR Program Administrator 
and the CC with respect to implementation of a proposed operating 
policy.  The panel will include one member selected by the CC, one 
member selected by NCRR, and a third member chosen by the other two 
members of the arbitration procedures in no way affect the awardee’s 
right to appeal an adverse determination in accordance with PHS 
regulations at 42 CFR Part 50, subpart D and HHS regulations at 45 CFR 
Part 16.
 
LETTER OF INTENT
 
Prospective applicants are asked to submit, by March 15, 2000, a
letter of intent that includes a descriptive title of the proposed
project, the name, address, and telephone number of the Principal
Investigator, the identities of other key personnel and participating 
institutions, and the number and title of this RFA in response to which 
the application may be submitted.  Although a letter of intent is not 
required, is not binding, and does not enter into the review of a 
subsequent application, the information that it contains allows NCRR 
staff to estimate the potential review workload and avoid conflict of 
interest in the review.
 
The letter of intent is to be sent to:
 
Jerry A. Robinson, Ph.D.
Comparative Medicine
National Center for Research Resources
One Rockledge Centre, Room 6164
6705 Rockledge Drive
Bethesda, MD  20892
Telephone:  (301) 435-0744
FAX:  (301) 480-3819
e-mail: [email protected]
 
APPLICATION PROCEDURES
 
The research grant application form PHS 398 (revised 4/98)is to be used 
in applying for this grant.  These forms are available at most 
institutional offices of sponsored research, from the Division of 
Extramural Outreach and Information Resources, NIH, 6701 Rockledge 
Drive, MSC 7910, Bethesda, MD 20892-7910, telephone (301) 710-0267 or 
E-mail [email protected], and from the program administrator listed 
under INQUIRIES.
 
The RFA label available in the PHS 398 application
form must be affixed to the bottom of the face page of the
application.  Failure to use this label could result in delayed
processing of the application such that it may not reach the review
committee in time for review.  In addition, the RFA title and
number must be typed on line 2a of the face page of the application
form and the YES box must be marked.

The sample RFA label available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been 
modified to allow for this change.  Please note this is in pdf format.
 
Submit a signed, typewritten original of the application,
including the Checklist, and three signed, photocopies, in one
package to:
 
Center for Scientific Review (CSR)
National Institutes of Health
Suite 1040
6701 Rockledge Drive MSC 7710
Bethesda, MD   20892-7710

Applicants who wish to use express mail or courier service should 
change the zip code to 20817.

At the time of submission, two additional copies of the application
must be sent to:
 
Jerry A. Robinson, Ph.D.
Comparative Medicine
National Center for Research Resources
One Rockledge Centre, Room 6164
6705 Rockledge Drive, MSC 7965
Bethesda, MD  20892 
(Zip Code 20817 for express mail)
 
Applications must be received by April 26, 2000.  If an application
is received after that date, it will be returned to the applicant
without review. The CSR will not accept any application in response to 
this RFA that is essentially the same as one currently pending initial 
review, unless the applicant withdraws the pending application.  The 
CSR will not accept any application that is essentially the same as one 
already reviewed.  This does not preclude the submission of substantial
revisions of applications already reviewed, but such applications
must include an introduction addressing the previous critique.
 
REVIEW CONSIDERATIONS
 
Upon receipt, applications will be reviewed for completeness by CSR and 
for responsiveness by the NCRR.  Incomplete or non-responsive 
applications will be returned to the applicant without further 
consideration.   
Applications that are complete and responsive will be evaluated for 
scientific and technical merit by an NCRR peer review committee 
convened in accordance with NIH peer review procedures.  As part of the 
initial merit review, all applications will receive a written critique 
and may undergo a process in which only those applications deemed to 
have the highest scientific merit, generally the top one half of 
applications under review, will be discussed, assigned a priority 
score, and receive a second level review by the National Advisory 
Research Resources Council, NCRR. 

Review Criteria
 
o  Significance.  What will be the impact of this resource on the AIDS 
biomedical research community?
 
o  Approach.  Are the conceptual framework, design, methods, and 
analyses adequately developed, well-integrated, and appropriate to the 
aims of the project?  Is the resource designed to effectively provide 
the required service to the research community?  Is the approach 
sufficient to ensure that the types of animals specified with the 
appropriate  SPF  validation will be made available.  Does the 
applicant acknowledge potential problem areas and consider alternative 
tactics?  Timelines and available number projections will be review 
considerations.  Documentation of the animal’s housing history will 
also be required.    
 
o  Innovation.  Is the design of the resource and the method of 
providing service innovative?
 
o  Investigator.  Is the investigator appropriately trained and well 
suited to carry out this work?  Is the work proposed appropriate to the 
experience level of the principal investigator and other researchers?

o   Environment.  Does the environment contribute to the probability of 
success of the resource?  Is there evidence of institutional support 
for the resource?
 
In addition to the above criteria, in accordance with NIH policy, all 
applications will be reviewed with respect to the following:
 
o   The reasonableness of the proposed budget and duration in relation 
to the proposed research.

o   The adequacy of the proposed protection for animals or the 
environment, to the extent they may be adversely affected by the 
project proposed in the application.

Schedule

Letter of Intent Receipt Date:    March 15, 2000
Application Receipt Date:         April 26, 2000
Peer Review Date:                 June 2000
Council Review:                   September 2000
Earliest Anticipated Start Date:  September 29, 2000
  
AWARD CRITERIA
 
Award criteria that will be used to make award decisions include:

o  scientific merit (as determined by peer review)
o  availability of funds
o  programmatic priorities

INQUIRIES
 
Inquiries concerning this RFA are encouraged.  The opportunity to
clarify any issues or questions from potential applicants is welcome.   
Direct inquiries regarding programmatic issues to:
 
Jerry A. Robinson, Ph.D.
Comparative Medicine
National Center for Research Resources
One Rockledge Centre, Room 6164
6705 Rockledge Drive
Bethesda, MD  20892
Telephone:  (301) 435-0744
FAX:  (301) 480-3819
e-mail: [email protected]
 
Direct inquiries regarding fiscal matters to:

Paul Karadbil
Office of Grants Management
National Center for Research Resources
6705 Rockledge Drive, Room 6086
Bethesda, MD   20892-7965
Telephone: (301) 435-0840
Email:  [email protected]
 
AUTHORITY AND REGULATIONS
 
This program is described in the Catalog of Federal Domestic
Assistance No. 93.849.  Awards are made under authorization of the 
Public Health Service Act, Title IV, Part A (Public Law 78-410, as 
amended by Public Law 99-158, 42 USC 241 and 285) and administered 
under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR 
Part 74.  This program is not subject to the intergovernmental review 
requirements of Executive Order 12372 or Health Systems Agency review.
 
The PHS strongly encourages all grant recipients to provide a smoke-
free workplace and promote the non-use of all tobacco products.  In 
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits 
smoking in certain facilities (or in come cases, any portion of a 
facility) in which regular or routine education, library, day care, 
health care, or early childhood development services are provided to 
children.  This is consistent with the PHS mission to protect and 
advance the physical and mental health of the American people.

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