# SECRETORY DEFENSES AGAINST GIARDIA LAMBLIA

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 1991 · $263,356

## Abstract

Knowledge of the interactions between Giardia Lamblia and its intestinal
milieu is extremely limited.  The hypothesis underlying this project is
that the great variations in clinical manifestations and duration of
giardiasis are due to parasite interactions with both immune and non-
immune components of this environment.  The long-term objective of these
investigations is to gain valuable basic information on the aspects of
parasites of parasite biology and host defenses that determine
colonization and persistence of trophozoites in the human small intestine.

The first Specific aim is to study the human secretory antibody response
in depth, focusing upon the isotype and antigenic specificity of
antibodies that inhibit trophozoite motility or attachment, and,
conversely, the effects of intestinal conditions on antigen expression,
interactions with antibody and trophozoite evasion of secretory defenses.
These studies should provide important new insights into the variable
severity of giardiasis.  To determine how the surface of trophozoites
adapts them to survive in the small intestine, we have cloned, expressed
in E.  coli and sequenced an important trophozoite surface antigen gene
(called 417).  Antibodies against the recombinant protein inhibit
trophozoite attachment and growth and immunoprecipitate trophozoite
surface proteins of -66 and 85 kD.  Therefore, in Specific Aim 2, we will
compare NH2-terminal amino acid sequences and peptide maps of purified p66
and p85 to determine their relationship to each other and to the 417 gene,
and ask whether and how they are post-translationally processed or
covalently modified and which epitopes are exposed to the host
environment.  Concomitantly, in Specific Aim 3, we will ask whether
inhibition of attachment by antibody to p417 is due to agglutination.
Next, we will assess the degree of cross-linking a native p66 and p85 on
the trophozoite surface, as well as their interactions with intestinal
proteases, bile salts, and mucins, and determine whether expression of p66
and p85 is regulated by intestinal stimuli.  In Specific Aim 4, we will
immunize animals orally with p417 and determine whether the secretory
antibody response is protective or whether trophozoites can effectively
evade it.  These studies should provide critical new insights into the
biologic and immunologic interactions of an important pathogen with the
complex intestinal environment.

## Key facts

- **NIH application ID:** 3129301
- **Project number:** 5R01AI019863-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **SAM.gov UEI:** UYTTZT6G9DT1
- **Principal Investigator:** FRANCES D. GILLIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $263,356
- **Award type:** 5
- **Project period:** 1982-09-01 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129301

## Citation

> US National Institutes of Health, RePORTER application 3129301, SECRETORY DEFENSES AGAINST GIARDIA LAMBLIA (5R01AI019863-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129301. Licensed CC0.

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