RFP No. NIH-NIAID-DMID-96-11


Title:  "MATERNAL IMMUNIZATION FOR THE PREVENTION OF INFECTIOUS
         DISEASES IN NEONATES AND INFANTS"

Issued by:    Carl R. Henn
              Contracting Officer
              NIH/NIAID
              Contract Management Branch
              Solar Building, Room 3C07
              6003 Executive Boulevard MSC 7610
              Bethesda, Maryland 20982-7610


DATE ISSUED:   AUGUST 24, 1995

PROPOSAL DATE DUE:   JANUARY 12, 1996,  4:00 P.M. (EST)


Ladies and Gentlemen:

The National Institute of Allergy and Infectious Diseases (NIAID)
invites interested parties to submit competitive offers for
evaluation leading to the award of a contract for "Maternal
Immunization for the Prevention of Infectious Diseases in
Neonates and Infants."  The Government contemplates the award of
one (1), five (5) year, cost-reimbursement, level of effort type
contract as a result of this RFP. 

Listed below are the four attachments of this Electronic RFP
package.  These documents represent all the necessary information
required for the submission of a proposal for this acquisition.
Following proposal submission and review, additional information
will be requested by the Contracting Officer from all offerors
who comprise the competitive range.  

IMPORTANT NOTE:  All proposals submitted in response to this RFP
must contain a completed copy of the Representations and
Certifications.  Offerors may obtain a copy of this document via
the NIH Gopher (go to the "Instructions for Proposal Submission"
directory, and then to the "Forms Required for Proposal
Submission" sub-directory), or by contacting Sara Southard at the
internet address listed below.

Although these documents contain sufficient information for your
organization to submit a proposal, if you intend to submit a
proposal in response to this RFP, IT IS ESSENTIAL THAT YOU
IMMEDIATELY NOTIFY SARA SOUTHARD OF THE NIAID CONTRACTING OFFICE
AT THE FOLLOWING INTERNET ADDRESS:  

     ss63e@nih.gov

IF YOU DO NOT NOTIFY THE CONTRACTING OFFICE OF YOUR INTEREST, YOU
WILL NOT RECEIVE NOTIFICATION OF AMENDMENTS ISSUED TO THE RFP. 
HOWEVER, ALL AMENDMENT WILL BE POSTED ON THE NIH GOPHER AND/OR
GRANT LINE SYSTEMS.

The documents included with this electronic RFP package are as
follows:

1.    Introduction, Background and Work Statement, dated
      August 2, 1995  (Attachment A).

2.    Reporting Requirements, dated August 2, 1995
      (Attachment B).

3.    Evaluation Factors for Award, dated August 2, 1995
      (Attachment C).

4.    Proposal Instructions and Information, dated
      August 2, 1995  (Attachment D)


In addition to the information listed above, a listing of the
applicable Government clauses/provisions, sample contract format,
and terms and conditions which will be incorporated into the
eventual contract document may be obtained either through
accessing the NIH Gopher system or by sending a request to Sara
Southard, Contract Specialist, using the internet electronic mail
address listed above.  

The original and twenty (20) copies of your technical proposal
and the original and five (5) copies of your business proposal
must be received by the Contracting Officer no later than January 
12, 1996, at 4:00 p.m. local time at the address listed in
Attachment D, Item 7.

You are reminded that the "Technical Proposal Cover Sheet" must
be completed in full detail and used as the cover sheet for each
copy of your technical proposal (A copy of this form is contained
in this NIH Gopher under the directory entitled "Instructions for
Proposal Submission.").  New policies require submission of more
detailed information than has been previously required. It is
important that you list all professional personnel and
organizations named in the proposal who have any role in the
proposed work, including: staff of the primary organization
(offeror), subcontractors, and collaborating organizations; and
consultants.  Organizational affiliation(s) must be indicated for
every person named.  You may use additional sheets, as needed,
following the format shown in the Technical Proposal Cover Sheet. 
This information will be used to ensure that there will be no
conflict of interest when selecting review committee members.

Your attention is further directed to the "Proposal Intent" form
contained in the Gopher sub-directory entitled "Forms Required
for Proposal Submission."  Please complete this form and return
it to this office by December 16, 1995.

Funds are not presently available for this requirement.  The
Government's obligation under a resulting contract is contingent
upon availability of appropriated funds from which payment for
contract purposes can be made.

If you have any additional questions regarding this RFP, please
contact Sara M. Southard through the internet using the
electronic mail address listed above or by phone 301/402-6289,
or fax 301/480-5253.

Sincerely,

  /s/

Carl R. Henn
Contracting Officer
Contract Management Branch
National Institute of Allergy
  and Infectious Diseases

Attachments:  A-D 


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RFP-NIH-NIAID-DMID-96-11

ATTACHMENT  A                                                     
8/2/95


          MATERNAL IMMUNIZATION FOR THE PREVENTION OF INFECTIOUS
                   DISEASES IN NEONATES AND INFANTS

                             WORK STATEMENT
                             ______________

INTRODUCTION
------------

The objective of this project is to further evaluate maternal
immunization as a prevention strategy for infectious diseases in
neonates and infants.  The work in this contract encompasses
Phase I and Phase II clinical trials of candidate vaccines of
various types, and related vaccine biology studies.  It is
anticipated that one contract will be awarded to interested
parties having the expertise and capability of undertaking
maternal immunization studies in a clinical setting. 


BACKGROUND
----------

The capacity to evaluate new and improved vaccine candidates in
an efficient and expeditious manner is an essential element of
the efforts of the Division of Microbiology and Infectious
Diseases of the National Institute of Allergy and Infectious
Diseases (NIAID).  The Institute has supported efforts to
evaluate control measures for infectious diseases during past
decades, including maternal immunization studies. 

Passively acquired humoral immunity for protection of neonates
and young infants against a wide variety of bacterial and viral
pathogens is extremely important. Within the infant itself,
humoral immunity develops early in ontogeny but is relatively
inefficient. By birth the infant is capable of responding to a
large number of antigens, but there is little response to others.
While significant progress has been made in the development of
more immunogenic bacterial and viral vaccines, prophylaxis in the
vulnerable neonate and young infant remains problematic. 
Attempts at inducing early protection by immunizing newborns have
been generally disappointing.  Maternal immunization resulting in
passive transfer of antibodies to the neonate provides a
potentially powerful alternative strategy for protection during
the vulnerable neonatal and early infant periods.

Perhaps the best known example has been the worldwide impact of
maternal immunization during pregnancy against tetanus.  Neonatal
tetanus remains a major cause of infant mortality in much of the
developing world, and active maternal immunization with tetanus
toxoid vaccine has been shown to be the most cost effective
intervention to prevent tetanus neonatorum. 

Other pathogens cause significant disease incidence, mortality
and morbidity in neonates and young infants. These include group
B streptococci, pneumococci, B. pertussis, and respiratory
viruses such as influenza and respiratory syncytial virus (RSV). 
H. influenzae type b (Hib) is a major cause of severe bacterial
infection in infants throughout the world, and until recently,
had been the most common cause of bacterial meningitis in
children in the United States.  The licensure of Hib
polysaccharide conjugate vaccines for infants beginning at two
months of age offers tremendous benefits for young infants, but
infants with low levels of passive maternally-derived antibody
may have a "window" of susceptibility to Hib disease.  Although
some Hib conjugate vaccines induce a good antibody response to
the primary dose, even those vaccines will not protect infants
until three months of age.   In many developing countries where
immunization with Hib conjugates is not routine or affordable, a
high proportion of invasive disease occurs within the first six
months of life.  The only source of protection for these infants
is maternally derived antibody.     

Pneumococcal infections are responsible for an estimated one
million deaths annually in children under five years of age in
the developing world.  A substantial proportion of this
pneumococcal disease occurs in infants under five months of age. 
Passive protection from maternally derived pneumococcal
antibodies has the potential for enormous economic impact in
developing countries.  Group B streptococci cause significant
mortality and devastating morbidity in neonates and young
infants.  The infant generally acquires the infection either in
utero or during the birth process, and is often profoundly ill by
24 hours of age.  Maternal immunization may be a highly effective
prevention strategy for neonatal GBS disease.

While much emphasis has been placed on bacterial pathogens, both
pregnant women and young infants have been documented to be
vulnerable to serious sequelae of viral infections.  Mortality
and serious morbidity resulting from influenza infection is
common for pregnant women and for infants.  Numerous studies have
shown that pregnant women will generate a normal response to
inactivated influenza vaccine and that a beneficial effect can be
generated by the passive transfer of specific influenza antibody
from mother to fetus. It is likely that passive antibody transfer
following maternal vaccination would be sufficient to protect
infants from developing influenza infection in the first months
of life.  Another potential source of protective antibodies is in
the breast milk of nursing mothers.  

A second viral respiratory pathogen of great significance in
infants and young children is RSV.  The greatest vulnerability to
life threatening disease caused by RSV occurs during the first
six months of life.  No vaccine is currently available which is
safe and immunogenic in very young infants.  The protective
effect of RSV-specific hyperimmune globulin has been demonstrated
in high risk infants.  Studies have also shown that naturally
acquired neutralizing antibodies against RSV will protect infants
from serious lower RSV infections.  However, only about 20
percent of women have titers high enough to protect their infants
through the first five months of life.  Immunization of pregnant
women with a safe and immunogenic RSV vaccine has the potential
to prevent or modify early infection with RSV in their infants. 

In summary, maternal immunization of the pregnant woman in the
third trimester of pregnancy can increase her antibody titers and
has the potential to provide her infant(s) with high levels of
protective antibody that could confer protection for the first
six months of life against relevant infections.  This approach
could eliminate that window of susceptibility of infants both in
the US and the developing world to Hib, pneumococcal, GBS,
pertussis and respiratory viral infections prior to the age when
protective, active antibody responses from active immunization
can be generated. 

This is a re-competition of a contract awarded to Baylor College
of Medicine in 1991 (N01 AI 15126).  Several Phase I and Phase II
trials of potential maternal vaccines have been initiated.  In
the previous contract, response to several candidate vaccines
(e.g. Hib conjugate vaccines, and a pneumococcal polysaccharide
vaccines) were examined, and the passive transfer of specific
antibodies evaluated.  A maternal immunization study evaluating a
decreased dose of Hib conjugate vaccine is currently underway. 
The contractor undertook a study evaluating the safety and
immunogenicity of a RSV subunit vaccine in post-partum women and
other healthy women of childbearing age.  A large study
evaluating immunization with Hib conjugate vaccines and
pneumococcal polysaccharide vaccine in women prior to pregnancy
was also undertaken in a Native American population.    

The Maternal Immunization Group (MIG) is intended to explore
research opportunities in maternal immunization with the goal
being the prevention of neonatal infectious disease.  Important
in the MIG is the epidemiologic surveillance of pathogens
circulating in the pregnant female population and neonatal
population that are of special interest to NIAID.  The MIG must
provide staff, expertise, a maternal and neonatal population, and
facilities to test a number of candidate vaccines developed by
industry and government/academic scientists. 


WORK STATEMENT
--------------

Independently and not as an agent of the Government, the
Contractor shall exert its best efforts to furnish all necessary
services, qualified professional and technical personnel,
materials, equipment, and facilities, not otherwise provided by
the Government under the terms of this contract as needed to
perform the work set forth below.

Specifically, the Contractor shall:

(1)   Establish and maintain the facilities and staff necessary to
      conduct prophylactic studies on candidate vaccines in
      pregnant human volunteers.  

      [NOTES TO OFFEROR: 
      A.    A well trained, committed and balanced team of staff to
            fulfill the requirements of this work statement is
            required.  The PI should have an M.D. and/or Ph.D.
            degree and have demonstrated experience in the clinical
            evaluation of vaccines and capacity to organize and
            administer a clinical study.  The team of professional
            personnel, including the nursing staff, should have
            composite expertise in pediatrics, neonatal infectious
            diseases, maternal immunization, obstetrics,
            immunology, clinical trials, host response to pathogens
            and vaccines, surveillance, immunodiagnostics and
            biostatistics. Effective nursing staff are critical to
            the success of vaccine trials and a designated Research
            Nurse Coordinator/Supervisor is desirable.  Individuals
            to be responsible for coordination of regulatory issues
            should be identified.  The technical personnel should
            be trained and experienced in performing assay and
            laboratory procedures. 

      B.    The NIAID Blue Ribbon Panel on Vaccine Research
            identified a need to train investigators in vaccine
            related clinical research. It is both feasible and
            desirable to provide training opportunities for
            suitable individuals through effort expended on the
            activities of this contract.  If appropriate and
            relevant, the offeror is free to propose inclusion of
            training opportunities for international and/or
            domestic scientists and clinicians.   

      C.    A summary curriculum vitae of each proposed
            professional and technical personnel should be included
            in the proposal. 

      D.    The offeror should describe how an existing clinical
            and laboratory facility can support the various
            studies, or describe the establishment of such
            facilities or collaborations to support the various
            studies.]  


(2)   Provide patients as required for Phase I and Phase II
      vaccine studies.  The target population for the vaccines is
      pregnant females. Test healthy adult non-pregnant female
      volunteers before progressing into the target population for
      candidate vaccines which have not been evaluated previously
      in adult volunteers. 

      [NOTES TO OFFEROR:  
      E.    It is anticipated that testing in healthy volunteers in
            different age groups will be performed by
            NIAID-supported Vaccine Evaluation Units, before
            progressing to the target population. However,
            depending on the vaccine or the study, there may be a
            need within the MIG for testing some candidate vaccines
            in seropositive or seronegative adult non-pregnant
            female volunteers. The anticipated number is 50 women
            per year.] 

      F.    For contracts dealing with clinical research, it is NIH
            policy that women and members of minority groups and
            their sub-populations must be included in all NIH
            supported biomedical and behavioral research projects
            involving human subjects, unless a clear and compelling
            rationale and justification is provided that inclusion
            is inappropriate with respect to the health of the
            subjects or the purpose of the research.  This new
            policy results from the NIH Revitalization Act of 1993
            (Section 492B of Public Law 103-43) and supersedes and
            strengthens the previous policies (Concerning the
            Inclusion of Women in Study Populations, and Concerning
            the Inclusion of Minorities in Study Populations) which
            have been in effect since 1990. The new policy contains
            some new provisions that are substantially different
            from the 1990 policies.  All investigators proposing
            research involving human subjects should read the "NIH
            Guidelines For Inclusion of Women and Minorities as
            Subjects in Clinical Research", which were published in
            the Federal Register of March 28, 1994 (FR 59, #59,
            pages 14508-14513).] 

(3)   Conduct Phase I and Phase II clinical trials to determine
      vaccine safety, reactogenicity, transplacental transfer of
      antibody, breast milk transfer of antibody, optimal dose,
      timing, immunogenicity and isotyping, depending on the
      vaccine being tested.

      [NOTES TO OFFEROR: 
      G.    Examples of the vaccines to be tested include, but are
            not restricted to:

                 i.   Vaccines for Group B Streptococci
                ii.   Respiratory syncytial virus vaccines
               iii.   Haemophilus influenzae type b conjugate and
                      polysaccharide vaccines
                iv.   Pneumococcal polysaccharide and conjugate
                      vaccines
  
      H.    There is interest not only in passive transfer through
            the placenta but also secretion of specific IgA
            antibodies in the milk. 

      I.    Issues of interest and importance include immunization
            schedules, dose, and transfer of
            functional/neutralizing antibodies.

      J.    The range of studies anticipated requires a minimum of
            120 subjects total per year.

      K.    Three sample protocols and consent forms should be
            submitted with the proposal and should demonstrate a
            thorough understanding of testing of the vaccines
            anticipated. For these protocols, particular attention
            should be paid to rationale for the study design and
            the development of optimized strategies.
      
      L.    Award of the contract does not commit the Government to
            approve the studies outlined and protocols presented in
            the proposal. The Project Officer will determine which
            studies are actually undertaken.] 

      M.    Although Phase III studies for vaccine efficacy may be
            considered in the event vaccines under study warrant
            it, a protocol for a Phase III trial should not be
            submitted with this proposal, nor should the costs for
            such a trial be included in the budget estimations.]

(4)   Conduct assays for antigens and antibodies (including
      antibody sub-classes) to determine volunteer eligibility,
      their baseline antigen/antibody levels on entry into a
      study, their response and the infant's response to the
      maternally-administered candidate vaccine, and if
      appropriate, the infant's response to active immunization. 

      [NOTE TO OFFEROR:  
      N.    Assays for antigens/antibodies to bacterial and viral
            vaccines will preferably be conducted by the contractor
            unless otherwise directed by the Project Officer. To
            ensure standardization, assays on selected sera samples
            may be undertaken by other contractors or employees of
            the Government, or by vaccine manufacturers. Should
            non-routine or "special" assays for antigens/antibodies
            be necessary, testing may be arranged by the
            Government, and the offeror will be asked to ship
            specimens to the appropriate site for assay.]

(5)   Collect and appropriately store sera and other body fluids
      from study participants. Amounts and type will depend upon
      individual protocols.

      [NOTE TO OFFEROR:  
      O.    Studies may require collection of blood by venipuncture
            from infants.]

(6)   Follow vaccinees and their infants for up to three years to
      document duration of antibody or immune response, resistance
      to infection in the event of natural infection within the
      community, and any potential hazards of immunization as
      requested by the Project Officer. 

      [NOTES TO OFFEROR:  
      P.    It is likely that all of the studies will require this
            type of follow-up.

      Q.    Consideration should be given to establishing a group
            to formally monitor the infants of vaccinated mothers
            for adverse events.  This may range from a safety
            monitor to the establishment of a Data and Safety
            Monitoring Board.]

(7)   Initiate or maintain an etiologic surveillance system to
      monitor relevant bacterial and viral infections in the
      populations proposed for study, in order to aid in the
      interpretation of the volunteers' and infants response to
      vaccination. 

      [NOTE TO OFFEROR:  
      R.    The pathogens of interest may change during the course
            of the contract.  The surveillance system should be
            flexible to allow for these changes.]

(8)   Prepare protocols, consent forms and other IND information
      for submission to the Project Officer and local
      Institutional Review Board (IRB) for approval and for NIAID
      to submit to the FDA as part of an Investigational New Drug
      (IND) package.  Amend as necessary after comments by the
      Project Officer, local IRB, the DMID Clinical and Regulatory
      Affairs Branch, and regulatory authorities.

(9)   Organize and administer the clinical and associated
      laboratory research activities of the contract. 
      a.    Plan, conduct, and report on the proposed clinical
            research and associated laboratory studies.  This shall
            include developing the specifics of experimental
            design, receiving and shipping of reagents and samples,
            coding of patients, reagents, and samples, and
            coordinating all of the subcontractors' activities (if
            applicable).  This shall also include conducting all
            clinical studies in compliance with DMID/NIAID policy
            and in coordination with the Clinical and Regulatory
            Affairs Branch, DMID/NIAID.
      b.    Manage the information generated, including
            transmission, storage, confidentiality, retrieval,
            validation, analysis, and publication.
      c.    Coordinate the preparation of all manuscripts and
            presentations involving data from the studies. 
            Establish a publication policy for results of
            multicenter studies, if applicable.  All publications
            shall acknowledge NIAID support and be submitted to the
            Project Officer for review, prior to publication.  The
            Project Officer shall have access to all data generated
            with the support of this contract.  
      d.    Establish and manage laboratory facility(ies) to
            support the various studies. 
      e.    Supervise, coordinate, and perform the project(s)


(10)  Attend and participate in one 2-day meeting per year in
      Bethesda to discuss results and future plans. 

      [NOTE TO OFFEROR:  
      S.    Travel, lodging and meal costs for the Principal
            Investigator and one co-investigator to attend this
            meeting should be included in the business proposal.]

(11)  Attend and participate in one 2 day meeting per year in
      Bethesda to discuss clinical trial coordination, and
      regulatory issues related to clinical trials.  

      [NOTE TO OFFEROR:  
      T.    Travel, lodging and meal costs for the individual
            serving as the research nurse coordinator or clinical
            trial coordinator and one other staff member to attend
            this meeting should be included in the business
            proposal.]

(12)  Organize and attend one 2-day meeting per year for purposes
      of protocol and study development and/or evaluation.

      [NOTE TO OFFEROR:  
      U.    This meeting will usually be held at the contractor's
            site.  Travel, lodging, meal and honoraria costs for
            five external scientific protocol/study
            developers/evaluators to attend this meeting should be
            included in the business proposal.  The individuals
            will be invited after consultation with the Project
            Officer.  For cost purposes, assume that two
            individuals will travel from Los Angeles, two will
            travel from Boston, and one will travel from Chicago.]

(13)  Report to the DMID Clinical and Regulatory Affairs Branch
      and to the Project Officer all adverse reactions to comply
      with FDA regulations.

[GENERAL NOTES TO OFFEROR:   
      V.    There may be occasion over the span of the proposed
            contract for multi-center efforts involving other DMID
            contractors so that protocols can be expeditiously
            completed.  The Project Officer will determine the
            necessity of this. 

      W.    Award of the contract does not commit the Government to
            approve ANY of the studies presented in the proposal. 
            The Project Officer will determine which studies are
            actually undertaken.  The Project Officer will also
            determine the necessity of arranging and attending
            meetings related to contract activities.] 


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RFP-NIH-NIAID-DMID-96-11

ATTACHMENT  B
8/2/95


                     REPORTING REQUIREMENTS
                     ______________________


The Contractor shall submit to the Contracting Officer and to the
Project Officer technical progress reports covering the work
accomplished during each reporting period.  These reports are
subject to the technical inspection and requests for clarification
by the Project Officer.  These shall be brief and factual and
prepared in accordance with the following format:

A.    Technical Reports

      In addition to those reports required by SECTION I and other
      terms of this contract, the Contractor shall prepare and
      submit the following reports in the manner stated below:

      (1)   Semi-Annual Technical Progress Reports - by the
            fifteenth working day of the month following the
            end of each six month period, the Contractor shall
            submit five (5) copies of a semi-annual Technical
            Progress Report, comprising four (4) copies to the
            Project Officer and one (1) copy to the Contracting
            Officer.  Such reports shall include the following
            specific information:

            a.    A cover page that lists the contract number and
                  title, the period of performance being reported,
                  the contractor's names and address, the author(s),
                  and the date of submission;

            b.    SECTION I - An introduction covering the purpose
                  and scope of the contract effort;

            c.    SECTION II - A description of overall progress plus
                  a separate description for each task or other
                  logical segment of work on which effort was
                  expended during the report period.  The description
                  shall include pertinent data and/or graphs in
                  sufficient detail to explain any significant
                  results achieved and preliminary conclusions
                  resulting from analysis and scientific evaluation
                  of data accumulated to date under the project;

            d.    SECTION III - Substantive performance; a
                  description of current technical or substantive
                  performance and any problems encountered and/or
                  which may exist along with proposed corrective
                  action.  Each clinical study should be reported
                  separately according to the number assigned by the
                  Project Officer.  An explanation of any difference
                  between planned progress and actual progress, why
                  the differences have occurred, and if behind
                  planned progress what corrective steps are planned.

            e.    An anticipated work plan for the following six
                  months.
            
            f.    A table reporting the numbers of women and minority
                  subjects enrolled in each clinical trial.  The
                  table should list the total number of subjects
                  enrolled and provide separate subtotals according
                  to ethnic descriptions (i.e., American Indian or
                  Alaskan Native; Asian or Pacific Islander; Black,
                  not of Hispanic origin; Hispanic; White, not of
                  Hispanic origin; and Other or unknown) and gender. 

            g.    Preprints, reprints, and abstracts shall be
                  submitted along with the report.

      SEMI-ANNUAL TECHNICAL PROGRESS REPORTS ARE NOT DUE FOR
      PERIODS IN WHICH AN ANNUAL OR FINAL REPORT IS DUE.

      (2)   Annual Reports - On the anniversary date of the contract,
            the Contractor shall submit eight (8) copies of an Annual
            Technical Progress Report, as above, comprising seven (7)
            copies to the Project Officer and one (1) copy to the
            Contracting Officer.  Such reports shall detail,
            document, and summarize the results of the entire
            contract work for the period covered.  These reports
            shall be in sufficient detail to explain comprehensively
            the results achieved.  Also to be included in the report
            is a summary of work proposed for the next reporting
            period.  Specific requirements, if any, are set forth in
            ARTICLES C:1, Work Statement.  A one page summary of each
            ongoing and completed protocol shall be submitted at this
            time.  An annual report will not be required for the
            period when the final report is due.  Preprints and
            reprints of papers and abstracts not submitted in the
            semi-annual report shall be submitted.  

      (3)   Final Report - By the expiration date of the contract,
            the Contractor shall submit eight (8) copies of a
            comprehensive Final Report, as above, comprising seven
            (7) copies to the Project Officer and one (1) copy to the
            Contracting Officer.  This final report shall detail,
            document and summarize the results of the entire contract
            work for the period covered.  This report shall be in
            sufficient detail to explain comprehensively the results
            achieved.  Additional specific requirements are set forth
            in ARTICLE C:1.  Preprints and reprints not included
            previously submitted shall be submitted.  

      (4)   Summary of Salient Results - With the annual/final
            reports the Contractor shall submit a summary (not to
            exceed 200 words) of salient results achieved during the
            performance of the contract. 

      (5)   Other Reports - The Contractor shall submit seven (7)
            copies of: a) a one page summary of each ongoing and
            completed protocol one year and thirty days after an
            individual IND goes into effect and b) yearly IRB
            approvals and supporting documents.  

B.    If the Contractor becomes unable to deliver the reports
      specified hereunder within the period of performance because
      of unforeseen difficulties, notwithstanding the exercise of
      good faith and diligent efforts in performance of the work,
      the Contractor shall give the Contracting Officer immediate
      written notice of anticipated delays with reasons, therefore.

C.    Technical Report Distribution
 
      Copies of the technical reports shall be submitted as follows:
      
 
      Type of   # of 
      Report   Copies   Addressee                       Due Dates
      ______   ______   _________                       _________

      Semi-       4     Project Officer                Semi-Annually
      Annual            DMID, NIAID, NIH               (Dates to be
      Progress          Solar Building, Room ____       specified 
                        6003 Executive Blvd. MSC 7630   in contract)
                        Bethesda, MD 20892-7630                    


      Semi-       1     Contracting Officer            Same as above
      Annual            CMB, NIAID, NIH
      Progress          Solar Building, Room 3C07
                        6003 Executive Blvd. MSC 7610
                        Bethesda, MD  20892-7610

      Annual      7     Same as P.O. above             Annually
                                                       (Dates to be
                                                        specified
                                                        in contract)
                                                                   
      Annual      1     Same as C.O. above             Same as above
      
      Final       7     Same as P.O. above             Expiration
                                                        date
      
      Final       1     Same as C.O. above             Same as above



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RFP-NIH-NIAID-DMID-96-11                                          

ATTACHMENT  C 
8/2/95


                    EVALUATION FACTORS FOR AWARD
                    ____________________________
 

A.    GENERAL

      The technical proposal will receive paramount consideration
      in the selection of the contractor for this acquisition. The
      evaluation will be based on the demonstrated capabilities of
      the prospective contractors in relation to the needs of the
      project as set forth in the RFP. The merit of each proposal
      will be evaluated carefully, based on responsiveness to the
      RFP and thoroughness and feasibility of the technical
      approach taken. Offerors must submit information sufficient
      to evaluate their proposals based on the detailed criteria
      listed below. Failure to provide the information required to
      evaluate the proposal may result in rejection of that
      proposal without further consideration.

B.    COMPARATIVE IMPORTANCE OF PROPOSALS

      You are advised that paramount consideration shall be given
      to the evaluation of the technical proposals, but not to the
      exclusion of cost considerations.  While high competency is
      sought, capabilities that exceed those needed for successful
      performance of the contract work/statement are not
      requested. In the event that the technical evaluation
      reveals that two or more offerors are approximately equal in
      technical ability, then the estimated cost of performance
      will become paramount. In any event, the Government reserves
      the right to make an award to the best advantage of the
      Government, cost and other factors considered.

C.    MANDATORY QUALIFICATIONS FOR FACILITIES

      Prior to award the offeror must document the adequacy and
      suitability of facilities for performing all of the
      requirements of the Work Statement. 

D.    TECHNICAL EVALUATION CRITERIA

      Proposals submitted in response to this RFP will be
      evaluated based on the following factors which are listed
      and weighted in order of their relative importance.
      Proposals will be judged solely on the written material
      provided by the offeror. 


Criterion Element                                          Weight

1. TECHNICAL APPROACH .....................................  80   

Documented technical adequacy and feasibility of the
proposed plans for Phase I and Phase II studies on
candidate vaccines, epidemiologic surveillance for
vaccine-relevant pathogens, performance of assays and
laboratory procedures. Adequacy, suitability and
availability of necessary populations as documented in
the proposal and demonstrated ability to recruit,
retain and follow appropriate samples of the study
populations.                 

      a)  Phase I and II trials:  This includes the               
      comprehensive approach for evaluating the vaccines
      cited as relevant examples in the Work Statement,
      suitability and originality of the sample clinical
      protocols, demonstrated ability to recruit, retain
      and follow appropriate populations, strategies for
      follow-up of vaccinees, appropriateness of consent
      forms and data collection forms, and handling of
      data, as required in the protocols and as
      requested in the Work Statement...................
      ........................ 50

      b) Associated laboratory studies: This includes                   
      plans for transporting and storing clinical
      specimens, performing assays on sera and other
      body fluids, and for other relevant laboratory
      procedures as required in the protocols and as
      requested in the Work Statement...................
      ........................ 20 

      c) Epidemiologic surveillance:  This includes                     
      the proposed methods and approaches for collecting
      focused epidemiologic data to support trials of
      vaccines, and evaluating risk factors for
      infection.........................................
      ........................ 10


2. PERSONNEL..............................................   20
                                                                              
Documented adequacy and relevance of expertise, experience,
education, and availability of personnel who will be assigned to
perform the requirements.  

      The PI should have an M.D. and/or Ph.D. degree and
      should provide documented evidence of experience in
      the clinical evaluation of vaccines in child-bearing
      aged women and pregnant women, and capacity to organize
      and administer a clinical study.  The team of professional
      personnel, including the nursing staff, should have
      composite expertise in pediatrics, neonatal infectious
      diseases, maternal immunization, obstetrics,
      immunology, clinical trials, host response to pathogens
      and vaccines, surveillance, immunodiagnostics and
      biostatistics.  The technical personnel should have
      documented training and experience in performing assay
      and laboratory procedures. The support staff should
      possess the requisite experience to perform their
      clerical and administrative duties. 


TOTAL POSSIBLE POINTS...................................... 100



E.   EVALUATION OF MINORITY GROUP AND GENDER REPRESENTATION
     (NIH 3185) (JUL 1994)

  This research project involves human subjects.  NIH Policy
requires that woman and members of minority groups and their
subpopulations must be included in the study population of
research involving human subjects, unless a clear and compelling
rationale and justification is provided with respect to the
health of the subjects or the purpose of the research.

  Where inclusion of women and minority populations is not
feasible, a detailed rationale and justification for exclusion of
one or both groups from the study population must be submitted
with the technical proposal.  The NIH will review the exclusion
rationale to determine if it is appropriate with respect to the
health of the subjects and/or the purpose of the research.  If
the rationale is not considered acceptable by the Government and
you are included in the competitive range, you will be afforded
the opportunity to further discuss and/or clarify your position
during discussions or include women and minorities in your best
and final (BAFO).  If your exclusion position is still considered
unacceptable by the Government after discussions, your proposal
may not be considered further for award.
                                              

*****************************************************************
*****************************************************************

  RFP-NIH-NIAID-DMID-96-11                                         

  ATTACHMENT D
  8/2/95


                      PROPOSAL INSTRUCTIONS AND INFORMATION
                      _____________________________________


  NOTICE TO OFFERORS:  This attachment contains proposal instructions  
  and information which is specifically related to this acquisition. 
  The information provided below is only a portion of the instructions 
  and notices required for the submission of a proposal.  Additional,
  more general, information and forms regarding proposal preparation
  are contained in the NIH Gopher directory entitled "Instructions
  for Proposal Submission."


    1.    52.216-1   TYPE OF CONTRACT  (APR 1984)

       The Government contemplates award of a cost-reimbursement
    contract resulting from this solicitation.


    2.    SIC CODE AND SMALL BUSINESS SIZE STANDARD 
          (NIH 3150) (JUN 1988)
              
      (a)  The standard industrial classification (SIC) code for this
    acquisition is 8733.

      (b) (1)  The small business size standard is $3.5  million
    dollars.

          (2)  The small business size standard for a concern which
    submits an offer in its own name, other than on a construction or
    service contract, but which proposes to furnish a product which
    it did not itself manufacture, is 500 employees.

      (c)  This requirement is NOT Set-Aside for Small Business.
    However, the Federal Acquisition Regulation (FAR) requires in
    every solicitation (except for foreign acquisitions) the
    inclusion of the Standard Industrial Classification (SIC) Code
    and corresponding size standard which best describes the nature
    of the requirement in the solicitation.
                   

    3.    NUMBER AND TYPE OF AWARD(S)  (NIH 2980) (APR 1984)

      It is anticipated that 1 award will be made from this
    solicitation and that award will be made on or about September 30,
    1996.  

      Further, it is anticipated that the award from this solicitation 
    will be a multiple-year cost reimbursement type contract with a    
    term of 5 years, and that incremental funding will be used. (Also, 
    see Incremental Funding Provision in this Section.)


    4.     ESTIMATE OF EFFORT  (NIH 2985) (APR 1984)

      To assist you in the preparation of your proposal, the
    Government considers the total effort to perform this contract to
    be approximately 35.5 person years.  This number is furnished for
    your information only and is not to be considered restrictive for
    proposal purposes.  As further assistance, it is estimated that  
    the above total labor effort is constituted as follows:

    Labor                            Percentages of Effort
    Category                Yr1     Yr2     Yr3     Yr4     Yr5  
    --------                ---     ---     ---     ---     ---   
    Prin. Invest.           30%     30%     30%     30%     30%   
    Investigators          250%    250%    250%    250%    250%    
    RNs                    200%    200%    200%    200%    200%  
    Technical & Support    230%    230%    230%    230%    230%  
                          _____   _____   _____   _____   _____  
    Subtotal               710%    710%    710%    710%    710%  

                              (Based on a 12-month work year)



    5.   COMPARATIVE IMPORTANCE OF PROPOSALS  (NIH 3171) (JUL 1994)

      You are advised that paramount consideration shall be given to
    the evaluation of technical proposals.  However, the Government
    reserves the right to make an award to the best advantage of the
    Government, cost and other factors considered.


    6.    52.233-2   SERVICE OF PROTEST  (NOV 1988)

      (a)  Protests, as defined in Section 33.101 of the Federal
    Acquisition Regulation, that are filed directly with an agency,
    and copies of any protests that are filed with the General
    Accounting Office (GAO) or the General Services Administration
    Board of Contract Appeals (GSBCA), shall be served on the
    Contracting Officer (addressed as follows) by obtaining written
    and dated acknowledgement of receipt from:
                                  
        Mr. Lewis Pollack

     
    Hand-Carried Address:

        NIH/NIAID
        Contract Management Branch
        Solar Building, Room 3C07
        6003 Executive Boulevard
        Rockville, Maryland  20852


    Mailing Address:

        NIH/NIAID
        Contract Management Branch 
        Solar Building, Room 3C07
        6003 Executive Boulevard MSC 7610
        Bethesda, Maryland  20892-7610


     (b)  The copy of any protest shall be received in the office 
    designated above on the same day a protest is filed with the
    GSBCA or within one day of filing a protest with the GAO.
               
         
    7.   PACKAGING AND DELIVERY OF THE PROPOSAL  (NIH 2995)
          (JUL 1994)

      Shipment and marking shall be as indicated below:

        External Package Marking:
        _________________________

        In addition to the address cited below, mark each package 
        as follows:

            "RFP No.  NIH-NIAID-DMID-96-11"

            "TO BE OPENED BY AUTHORIZED GOVERNMENT PERSONNEL ONLY"

      
      PLEASE READ THE FOLLOWING INFORMATION CAREFULLY:
    
         Number of Copies:
         ________________

         Technical Proposal:  Original and 20 copies.
   
         Business Proposal:  Original and 5 copies.
     

        If hand delivered or delivery service
        -------------------------------------

           NIH/NIAID
           Contract Management Branch
           Solar Building, Room 3C07
           6003 Executive Boulevard
           Rockville, Maryland 20852

        If using U.S. Postal Service
        ----------------------------

           NIH/NIAID
           Contract Management Branch
           Solar Building, Room 3C07
           6003 Executive Boulevard MSC 7610
           Bethesda, Maryland 20982-7610


      * THE ORIGINALS MUST BE READILY ACCESSIBLE FOR DATE STAMPING 
       PURPOSES
      
    NOTE:  The U.S. Postal Service's "Express Mail" does not deliver
    to the Rockville, Maryland address.  Any package sent to the
    Rockville address via this service will be held at a local post
    office for pick-up.  THE GOVERNMENT IS NOT RESPONSIBLE FOR
    PICKING UP ANY MAIL AT A LOCAL POST OFFICE.  If a proposal is not
    received at the place, date, and time specified herein, it will
    be considered a "late proposal".


    8.   EVALUATION OF PROPOSALS  (NIH 3125) (JUL 1986)

      The Government will evaluate Proposals in accordance with the
    evaluation criteria set forth in Attachment C (Proposal
    Evaluation Criteria) of this RFP document.


    9.   PHSAR  352.280-1(a)  NOTICE TO OFFERORS OF REQUIREMENTS OF
         45 CFR PART 46, PROTECTION OF HUMAN SUBJECTS  (SEP 1985)
                                               
      (a)  Copies of the Department of Health and Human Services
    (Department) regulations for the protection of human subjects, 45
    CFR Part 46, are available from the Office for Protection from
    Research Risks (OPRR), National Institutes of Health, Bethesda,
    Maryland 20892.  The regulations provide a systematic means,
    based on established ethical principles, to safeguard the rights
    and welfare of individuals who participate as subjects in
    research activities supported or conducted by the Department.

      (b)  The regulations define a human subject as a living
    individual about whom an investigator (whether professional or
    student) conducting research obtains (1) data through
    intervention of interaction with the individual, or (2)
    identifiable private information.  The regulations extend to the
    use of human organ, tissue, and body fluids from individually
    identifiable human subjects as well as to graphic, written, or
    recorded information derived from individually identifiable human
    subjects.  The use of autopsy materials is governed by applicable
    State and local law and is not directly regulated by 45 CFR Part
    46.

      (c)  Activities in which the only involvement of human subjects
    will be in one or more of the categories set forth in 45 CFR
    46.101(b)(1-6) are exempt from coverage.

      (d)  Inappropriate designations of the non-involvement of human
    subjects or of exempt categories of research in a project may
    result in delays in the review of a proposal.  The Public Health
    Service will make a final determination of whether the proposed
    activities are covered by the regulations or are in an exempt
    category, based on the information provided in the proposal.  In
    doubtful cases, prior consultation with OPRR, (telephone:
    301-496-7163), is recommended.

      (e)  In accordance with 45 CFR Part 46, prospective Contractors
    being considered for award shall be required to file with OPRR an
    acceptable Assurance of Compliance with the regulations,
    specifying review procedures and assigning responsibilities for
    the protection of human subjects.  The initial and continuing
    review of a research project by an institutional review board
    shall assure that the rights and welfare of the human subjects
    involved are adequately protected, that the risks to the subjects
    are reasonable in relation to the potential benefits, if any, to
    the subjects and the importance of the knowledge to be gained,
    and that informed consent will be obtained by methods that are
    adequate and appropriate.  Prospective Contractors proposing
    research that involves human subjects shall be contacted by OPRR
    and given detailed instructions for establishing an institutional
    review board and filing and Assurance of Compliance.

      (f)  It is recommended that OPRR be consulted for advice or
    guidance concerning either regulatory requirements or ethical
    issues pertaining to research involving human subjects.


    10.  PHSAR 352.280-2(a)   NOTICE TO OFFERORS OF REQUIREMENT FOR
         ADEQUATE ASSURANCE OF PROTECTION OF VERTEBRATE ANIMAL
        SUBJECTS  (SEP 1985)
          
      The PHS Policy on Humane Care and Use of Laboratory Animals by
    Awardee Institutions establishes a number of requirements for
    research activities involving animals.  Before a PHS award may be
    made to an applicant organization, the organization shall file,
    with the Office for Protection from Research Risks (OPRR),
    National Institutes of Health (NIH), PHS, a written Animal
    Welfare Assurance which commits the organization to comply with
    the provisions of the PHS Policy on Humane Care and use of
    Laboratory Animals by Awardee Institutions, the Animal Welfare
    Act, and the Guide for the Care and Use of Laboratory Animals
    prepared by the Institute of Laboratory Animal Resources.  In
    accordance with the PHS Policy on Humane Care and Use of
    Laboratory Animals by Awardee Institutions, applicant
    organizations must establish a committee, qualified through the
    experience and expertise of its members, to oversee the
    institution's animal program, facilities and procedures.  No PHS
    award involving the use of animals shall be made unless the   
    Animal Welfare Assurance has been approved by OPRR.  Prior to
    award, the contracting officer will notify Contractor(s) selected
    for projects that involve live vertebrate animals that an Animal
    Welfare Assurance is required.  The contracting officer will
    request that OPRR negotiate an acceptable Animal Welfare
    Assurance with those  Contractor(s).  For further information,
    OPRR may be contacted at NIH, Bethesda, Maryland 20892
    (301-496-7163).


    11.   PRIVACY ACT  (NIH 3131) (JUL 1994)

      The Privacy Act of 1974 (P.L. 93-579) requires that a Federal
    agency advise each individual whom it asks to supply information,
    the authority which authorizes the solicitation, whether
    disclosure is voluntary or mandatory, the principal purpose or
    purposes for which the information is intended to be used, the
    uses outside the agency which may be made of the information, and
    the effects on the individual, if any, of not providing all or any
    part of the requested information.

      The NIH is requesting the information called for in this RFP
    pursuant to the authority provided by Sec. 301(g) of the Public
    Health Services Act, as amended, and P.L. 92-218, as amended.

      Providing the information requested is entirely voluntary.  The
    collection of this information is for the purposes of conducting
    an accurate, fair, and adequate review prior to a discussion as to
    whether to award a contract.

      Failure to provide any or all of the requested information may
    result in a less than adequate review.

       In addition, the Privacy Act of 1974 (P.L. 93-579, Sec. 7)
    requires that the following information be provided when
    individuals are requested to disclose their social security
    number.

      Provision of the social security number is voluntary.  Social
    security numbers are requested for the purpose of accurate and
    efficient identification, referral, review and management of NIH
    contracting programs.  Authority for requesting this information
    is provided by Section 305 and Title IV of the PHS Act, as
    amended.

      The information provided by you may be routinely disclosed for
    the following purposes:

       - to the cognizant audit agency and the General Accounting
        Office for auditing.

       - to the Department of Justice as required for litigation.

       - to respond to congressional inquiries.

       - to qualified experts, not within the definition of Department
        employees, for opinions as a part of the review process.


    12.   INCLUSION OF MINORITIES AND WOMEN AS SUBJECTS IN RESEARCH
          PROPOSAL INSTRUCTIONS  (NIH 3475) (JUL 1994)

      It is the policy of NIH that woman and members of minority
    groups and their subpopulations must be included in all NIH
    supported biomedical and behavioral research projects involving
    human subjects, unless a clear and compelling rationale and
    justification is provided that inclusion is inappropriate with
    respect to the health of the subjects or the purpose of the
    research.  This new policy results from the NIH Revitalization Act
    of 1993 (Section 492B of Public Law 103-43) and supersedes and
    strengthens the previous policies (Concerning the Inclusion of
    Women in Study Populations, and Concerning the Inclusion of
    Minorities in Study Populations) which have been in effect since
    1990.  The new policy contains some new provisions that are
    substantially different from the 1990 policies.

      All investigators proposing research involving human subjects
    should read the "NIH Guidelines For Inclusion of Women and
    Minorities as Subjects in Clinical Research" which have been
    published in the Federal Register of March 28, 1994 (FR 59
    14508-14513), [(this was reprinted to correct typesetting errors
    from the Federal Register dated March 9, 1994 (FR 59  
    11146-11151)], and reprinted in the NIH GUIDE FOR GRANTS AND
    CONTRACTS of March 18, 1994, Volume 23, Number 11.

      Offerors may obtain copies from these sources or from the
    contact person listed in the RFP.

      Unless otherwise specified in this solicitation, the Government
    has determined that the work set forth herein does not involve a
    gender specific study or a single or limited number of minority
    population groups.  Therefore, the NIH believes that the inclusion
    of women an minority population is appropriate for this project.
    (See Attachment C of this RFP for more information about
    evaluation factors for award.)

      The format for the Annual Technical Progress Report (See
    Technical Reporting Requirements contained in Attachment B of
    this RFP) shall be used in proposal preparation.


    13.   ADDITIONAL PROPOSAL INSTRUCTIONS

      A listing of additional instructions and notices required for    
      proposal preparation is provided below.  The full text 
      versions of these provisions are contained in the NIH Gopher
      directory entitled "Instructions for Proposal Submission".

         - NOTICE LISTING SOLICITATION PROVISIONS INCORPORATED
            BY REFERENCE
         - 52.252-1  SOLICITATION PROVISIONS INCORPORATED BY
            REFERENCE  (JUN 1988)
         - COMMITMENT OF PUBLIC FUNDS  (NIH 2455) (JUL 1986)
         - COMMUNICATIONS PRIOR TO CONTRACT AWARD  (NIH 2345) 
            (FEB 1990)
         - RELEASE OF INFORMATION  (NIH 3170) (JUL 1994)
         - PREPARATION COSTS  (NIH 3173) (JUL 1994)
         - PHSAR 352.215-10  LATE PROPOSALS, MODIFICATIONS OF          
            PROPOSALS AND WITHDRAWALS OF PROPOSALS  (NOV 1986)
         - CONTRACT CLAUSES  (NIH 3120) (JUN 1986)
         - FORMAT AND CONTENT OF PROPOSALS  (NIH 3121) (JUL 1994)
         - SEPARATION OF TECHNICAL AND BUSINESS PROPOSALS
            (NIH 3122) (JUL 1994)
         - ALTERNATE PROPOSALS  (NIH 3123) (JUL 1994)
         - CONFIDENTIALITY OF PROPOSALS  (NIH 3124) (JUL 1994)
         - USE OF THE METRIC SYSTEM OF MEASUREMENT  (NIH 3126)
            (JUL 1994)
         - SELECTION OF OFFERORS  (NIH 3130) (JUL 1986)
         - SMALL BUSINESS AND SMALL DISADVANTAGED BUSINESS
            SUBCONTRACTING PLAN  (NIH 3135) (JUL 1986)
         - REIMBURSEMENT OF COSTS FOR INDEPENDENT RESEARCH AND 
            DEVELOPMENT PROJECTS  (NIH 3165) (JUL 1994)
         - SALARY RATE LIMITATION INFORMATION FOR OFFERORS
            (NIH 3101) (OCT 1994)
         - TECHNICAL PROPOSAL INSTRUCTIONS  (NIH 3500) (JUL 1994)
         - TECHNICAL DISCUSSIONS  (NIH 3505) (JUL 1994)
         - TECHNICAL EVALUATION  (NIH 3510) (JUL 1994)
         - ADDITIONAL TECHNICAL PROPOSAL INFORMATION   
            (NIH 3165) (JUL 1994)
         - OTHER CONSIDERATIONS  (NIH 3520) (JUL 1994)
         - COST AND PRICING DATA  (NIH 3600) (JUL 1994)
         - QUALIFICATIONS OF THE OFFEROR  (NIH 3615) (JUL 1994)
         - PROPERTY/EQUIPMENT/FACILITIES  (NIH 3620) (JUL 1994) 
         - ROYALTIES  (NIH 3625) (JUL 1994)
         - FINANCIAL CAPACITY  (NIH 3630)  (JUL 1994)
         - SUBCONTRACTORS  (NIH 3635)  (JUL 1994)
         - INCREMENTAL FUNDING  (NIH 3640) (JUL 1994)
         - REPRESENTATIONS AND CERTIFICATIONS  (NIH 3645) (JUL 1994)
         - NOTICE TO OFFERORS - FORMS/FORMATS/ATTACHMENTS   
            (NIH 3145) (JUL 1986)