# Rational design of an adhesin-based pneumococcal vaccine targeting colonization

> **NIH NIH R15** · MISSISSIPPI STATE UNIVERSITY · 2020 · $417,206

## Abstract

PROJECT SUMMARY/ABSTRACT
 Currently licensed pneumococcal conjugate vaccines have been successful in preventing invasive
disease; however, overall colonization rates have remained fairly constant and serotype replacement by non-
vaccine serotypes is now common. This along with other weaknesses points to a need for a broadly protective
protein-based vaccine. Current protein candidates for such a vaccine have primarily been identified based on
their immunogenicity during natural infection, but this strategy overlooks one critical fact: Humans are
repetitively colonized by pneumococcus throughout their lives. This indicates that a majority of highly antigenic
pneumococcal proteins may elicit strong but not protective immune responses against colonization. The long-
term goal is to develop a broadly and consistently protective vaccine against all forms of pneumococcal
disease. The overall objective of this proposal is to identify highly conserved pneumococcal adhesins vital for
colonization but poorly immunogenic in natural infections. The central hypothesis is that vaccination with
pneumococcal adhesins, poorly immunogenic during natural infections, will provide supplemental immunity for
preventing pneumococcal adherence and colonization, the prerequisite for all pneumococcal disease. This
hypothesis is based on strong preliminary data obtained by our group and others that show a critical role for
surface adhesins in colonization and subsequent pneumococcal infections. The rationale for the proposed
research is that identifying novel conserved adhesin/host cell interactions will allow for the design a broadly
protective protein-based vaccine effective at limiting colonization. To accomplish the objective of this
application, the hypothesis will be tested by pursuing the following three specific aims: 1) Identify conserved
pneumococcal adhesins differentially expressed between planktonic and biofilm growth; 2) Determine the role
of pneumococcal adhesins in adherence and colonization; and 3) Determine the protective effect of vaccination
with pneumococcal adhesins. The approach is innovative, in the applicant’s opinion, because it represents a
substantive departure from the status quo by focusing specifically on pneumococcal proteins predicted to be
surface-expressed and play a role in colonization, without overlooking candidates with limited immunogenicity.
This contribution is significant because it will identify novel targets that can be exploited to prevent
pneumococcal colonization in a capsule-independent fashion, thus overcoming several shortcomings of current
vaccines and taking a vertical step forward in the field. The streamlined workflow of developing a novel vaccine
using reverse vaccinology and biomedical technologies will engage undergraduate and graduate students from
across Mississippi, a traditionally underrepresented state, in the advancement biomedical research, thereby
fulfilling the goals of the AREA grant program and also contrib...

## Key facts

- **NIH application ID:** 9813424
- **Project number:** 1R15AI142537-01A1
- **Recipient organization:** MISSISSIPPI STATE UNIVERSITY
- **Principal Investigator:** Keun Seok Seo
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $417,206
- **Award type:** 1
- **Project period:** 2020-09-17 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9813424

## Citation

> US National Institutes of Health, RePORTER application 9813424, Rational design of an adhesin-based pneumococcal vaccine targeting colonization (1R15AI142537-01A1). Retrieved via AI Analytics 2026-06-23 from https://api.ai-analytics.org/grant/nih/9813424. Licensed CC0.

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