# Targeting Pneumococcal Colonization

> **NIH NIH R21** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $254,250

## Abstract

Streptococcus pneumoniae (Spn, the pneumococcus) remains a leading cause of respiratory tract
and invasive infection. While vaccination with capsular polysaccharide-based vaccines has
decreased the high burden of Spn disease, this approach fails to target the majority of Spn, which
are non-vaccine serotypes. Unfortunately, the development of more broadly-acting, serotype-
independent vaccines that focus on preventing Spn disease has proven to be elusive. The
required first step for Spn-host interaction, however, is colonization of the mucosal surfaces of
the upper airways. Our premise is that interrupting colonization will have the greatest overall
impact on Spn disease and offers new, unexplored possibilities for prevention. We have optimized
an infant mouse model of Spn colonization that has allowed the application of Tn-Seq transposon
mutagenesis to interrogate the entire Spn genome to identify loci affecting colonization. The
complete dataset of non-essential Spn genes affecting colonization was then compared to
bacterial surface factors that are immunogenic during human infection. Defined mutants in each
of these candidates were constructed and tested in both infant and adult murine models of
colonization. Seven loci expressing proteins of known function that modify the bacterial surface
or host substrates were validated as required for efficient colonization. These proteins are all
members of the Spn core genome present in all strains and show minimal sequence variation
across isolates. Our hypothesis is that immunity to these candidates, alone or in combination, will
interrupt Spn colonization. This hypothesis will be tested first by immunization with recombinant
protein in adjuvant (SC or IN) to maximize antibody responses. Murine antibody will be used to
confirm surface localization and to explore its ability to block protein function using in vitro assays.
Immune mice v. adjuvant alone controls will then be challenged IN or via pup-to-pup transmission
to assess protection from colonization with diverse strains. In future studies, candidates validated
in the murine model can be investigated using experimental human pneumococcal carriage to
bridge the critical step from animal to human testing. Thus, our proposal takes a novel approach,
targeting colonization, to the ongoing public health problem of the pneumococcus.

## Key facts

- **NIH application ID:** 9943177
- **Project number:** 1R21AI150867-01
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Jeffrey Neal Weiser
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $254,250
- **Award type:** 1
- **Project period:** 2020-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9943177

## Citation

> US National Institutes of Health, RePORTER application 9943177, Targeting Pneumococcal Colonization (1R21AI150867-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9943177. Licensed CC0.

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