**Amendment #3 (Questions & Answers)**

**This Amendment provides questions submitted by potential offerors and
the responses provided by the NIAID. [The responses are offered for
information only and do not modify or become part of this
solicitation.]{.mark} This Amendment will be updated to add any further
questions and their related responses. All potential offerors are
advised to refer back to this Amendment, 3 for additional Questions and
Answers.**

"Allergen & T-Cell Reagent Resources for the Study of Allergic Diseases"

+--------------------------+-------------------------------------------+
| **Amendment No.:**       | 3 [(1^st^ Posting)]{.mark}                |
+--------------------------+-------------------------------------------+
| **Amendment Issue        | October 20, 2006 (Questions 1 -- 9)       |
| Date:**                  |                                           |
+--------------------------+-------------------------------------------+
| **Proposal Due           | November 13, 2006, at 3:00 P.M., local    |
| Date/Time:**             | time                                      |
+--------------------------+-------------------------------------------+
| **Issued By:**           | Charles W. Grewe                          |
|                          |                                           |
|                          | Contracting Officer                       |
|                          |                                           |
|                          | OA/DEA/NIAID/NIH/DHHS                     |
|                          |                                           |
|                          | 6700-B Rockledge Drive, Room 3214,        |
|                          |                                           |
|                          | Bethesda, Maryland 20892-7612             |
+--------------------------+-------------------------------------------+
| **Points of Contact:**   | <lcoleman@niaid.nih.gov>                  |
|                          |                                           |
|                          | Lisa Coleman, Contract Specialist         |
+--------------------------+-------------------------------------------+

![](media/image1.png){width="6.25in" height="0.10416666666666667in"}

**Offerors must acknowledge receipt of the [first posting of Amendment
#3]{.underline}, on each copy of the proposal submitted. Failure to
receive your acknowledgment of this Amendment may result in the
rejection of your proposal.**

**The hour and date specified for receipt of proposals HAS NOT been
extended.**

![](media/image1.png){width="6.25in" height="0.10416666666666667in"}

**THE FOLLOWING PAGES PROVIDE ANSWERS CONCERNING A NUMBER OF INQUIRIES
WE HAVE RECEIVED FOR THE ABOVE NUMBERED ACQUISITION:**

1.  Page 87 of the description indicates "In addition, most of the more
    than 460 known allergens have not yet been fully developed as T cell
    reagents." From which resource is the number 460 pulled from?

> **Referring to Attachment 3, Introduction, Paragraph 3. The 460 known
> allergens are from a list compiled internally, from several sources,
> at the time of writing this RFP, and one that continues to grow. The
> RFP states NIH is looking for proposals to study those allergens
> associated with clinical relevance. Overall, the evaluation of the
> importance for/of a specific allergen will be part of the Technical
> Evaluation, as described in the RFP (by an independent SRG). This will
> be true for proposals looking for a novel allergen or t-cell epitope
> mapping of existing allergens.**
>
> **Database sources for allergens are: Allergopharma Allergen Database
> at [www.allergen.org/list.htm](http://www.allergen.org/list.htm)**

2.  There are a few questions relating to the BAA, and the experiments
    mentioned in the technical objectives, relating to (attachment 4,
    page 1; research area 2; point 3) "characterization of peptide
    binding to human allergen specific T cell." We were unclear whether
    this meant to be binding of the candidate epitopes to human MHC? Or
    alternatively, making tetramers incorporating the peptides? Or
    measuring the functional affinity of allergenic T cells by
    performing antigen dose response titrations?

> Please see page 2 of Attachment 4, Section -- Specific Technical
> Requirements Research Area 2, items numbered 1-5. Please note that the
> purpose of this RFP is to identify those epitopes from clinically
> relevant allergenic sources. This is explained in Attachment 6,
> Appendix A, page 5. Additionally, the offeror will need to justify the
> selection of the clinically relevant allergen source.

3.  In the BAA, there is a comment under "Examples of research that are
    NOT responsive to Research Area 1 and Research Area 2 include:
    additional characterization of molecules found only to contain
    adjuvant activity." At this time, I am not sure whether the pollen
    NADPH oxidase falls into this arena or not.

> As detailed in the RFP (Attachment 4, page 1, Research Area 1) the
> scope of activities to be performed shall include the following:

1.  Identification and characterization of novel allergens, including
    novel modifications to known allergens, isolated from clinically
    important sources such as plants, insects, and food.

2.  Validation of these novel allergens using appropriate in vitro
    methods.

3.  Prioritization of the biological significance of the novel allergens
    through relevant in vitro cell activation assays; and,

4.  Determination of the chemical and molecular structures of these
    novel allergens.

> Furthermore, as detailed in the RFP (Attachment 4, page 2, Research
> Area 1, number 3) it states "Additional characterization of molecules
> containing only adjuvant activity will [not]{.underline} be
> supported."
>
> Therefore, the cloning of the adjuvant NADPH oxidase, from allergenic
> and non-allergenic sources would [not]{.underline} qualify for
> submission to this RFP.

Question 4 Please provide a "List of Bidders/Vendors" for this project
so we may touch base for any subcontracting opportunities.

It is not the policy of the NIH to release potential offerors (bidders).
If you are interested in subcontracting opportunities, please provide a
statement that allows consent for NIAID to share your contact
information with any potential offerors who submit an "Intent to
Respond" to this RFP. Please confirm the contact name, name of the
organization, address, and phone number. Your information will be passed
on if potential offerors request information about potential
subcontractors.

Question 5 In the Western half of the US a major allergen is sagebrush
(Artemisia tridentata). The geographical expanse of the growing area,
the numbers of people exposed and the inherent allergenicity of the
pollen make sagebrush a major allergen. Please provide clarification.

Submitting a proposal for a novel allergen specifically from the
sagebrush is appropriate. However, please remember that the proposal
will be evaluated on many factors including the "intended clinically
relevant allergenic source." This point is mentioned on page 4 of
Attachment 3 BAA description, on page 1 of Attachment 4, Research And
Technical Objectives and page 1 of Attachment 6, appendix A.

Question 6 Please address a specific statement in the BAA under
Attachment 3, page 4: "Examples of research that are not responsive to
Research Area 1 and Research Area 2 include: Research limited solely to
confirmatory studies of previous mapped allergen(s)." Some allergens
that may be studied have been examined by other researchers. For
example, Phl p 5 (from timothy grass) has been studied fairly
extensively by others. In addition, T cell epitopes from allergen such
as Ara h 2 (peanut), Der p 1, Der p 2 and Ves v 5 (yellow jacket) have
also been mapped.

> A proposal from an offeror should not be "...for confirmatory studies
> of mapped allergens." This is not to say that work cannot be conducted
> where the investigator uses previously mapped allergens for/as
> comparison purposes, e.g. technique or method evaluations, for
> standardization and/or reference purposes. However, the proposed plan
> cannot be exclusively direct at confirmatory studies of known mapped
> allergens. An independent evaluation of the proposal will be conducted
> and a weighted score assigned to the science associated with the
> proposed allergen and its clinical relevance. The overall score will
> be assessed among all proposals.

Question 7 I am curious about NIAID's enthusiasm on identifying Der p 1,
Der p 2 epitopes, as well as epitopes from cat and dog danders.

> Cat and dog danders: yes, in general the NIH is interested. Again, the
> Offeror should understand that the proposal will be evaluated by an
> independent panel on the science and clinical relevance of the
> allergen. The overall score of the proposal will be assessed among all
> proposals. Therefore, the Offeror should provide all the relevant
> information for the clinical significance of the proposed allergen.

Question 8 Are studies employing HLA Class II transgenic mice for
allergen T cell epitope mapping responsive to the RFP?

> As [one]{.underline} of the tools to be used in the overall proposal,
> yes-the use of transgenic MHC Class II mice would be responsive. If
> the transgenic mice were the [only]{.underline} tool used in the
> proposal -- no, this would not be responsive. Any T cell epitope
> identified using any screening method, including transgenic mouse
> models, must be validated with human allergen specific T cells.

Question 9 The announcement describes, under Research Area 1, the
identification, validation and characterization of novel allergens, also
from insects, including the determination of their molecular structure
and/or composition. Will this be restricted to fat soluble allergens or
allergens modified with carbohydrates? Or major allergens of clinical
relevance that are water-soluble can also be included?

> No, the solicitation is not restricted to just fat soluble or
> carbohydrate modified allergens. Major allergens of clinical relevance
> that are water soluble will meet the requirement. However, it is
> limited to \'novel\' or \'new\' allergens. The RFP does not support
> research into the characterization of existing allergens. So, if the
> allergen has already been published and defined, the further detailed
> characterization would not fit under Research Area 1.