# Utilization of the adjuvant effect of CRM197 protein to develop a trivalent protein-vaccine against Streptococcus pneumoniae infections

> **NIH NIH R21** · UNIVERSITY OF FLORIDA · 2022 · $190,625

## Abstract

Abstract
Streptococcus pneumoniae (Spn) is a major respiratory pathogen that causes a spectrum of non-invasive (otitis
media, sinusitis, pneumonia) as well as invasive (sepsis, meningitis) diseases. Despite a decline in the overall
Spn disease burden caused by currently available vaccines (Spn/pneumococcal conjugate vaccines: PCVs),
Spn diseases continue to occur and remain a significant medical problem. Due to the emergence of new,
replacement serotypes (STs), Spn protein-based vaccines that aim to protect against Spn diseases in a
serotype-independent manner are considered to be the best solution. However, there is a pressing need to
develop novel adjuvants that can enhance antibody response and its biological function directed against Spn
proteins antigens, given the target populations of these vaccines are children, elderly, and immunocompromised
individuals.
We developed a trivalent protein vaccine involving two well-known Spn vaccine candidates, N-terminal
pneumococcal surface protein A (PspA) and domain 4 of pneumolysin (PlyD4), genetically fused with diphtheria
The purpose of choosing N-PspA and PlyD4 is based on
their prior characterization in animal models of vaccination with demonstratable efficacy against Spn colonization
and sepsis. Therefore, genetic fusion of CRM197 to proven Spn candidates will help compare the CRM197 driven
enhancement of immunogenicity and protective efficacy with published work and to expand the platform to
include other promising vaccine candidates subsequently.
detoxified antigen CRM197 (CRM197-N-PspA-PlyD4).
Our preliminary data shows that the genetic fusion of
CRM197 significantly enhanced (several folds) the antibody titers against N-terminal PspA. Additionally, the
genetic fusion (trivalent vaccine) led to a significant increase in the binding of antisera to Spn bacteria, a measure
of antibody functionality. Furthermore, the incubation of Spn bacteria with trivalent antisera significantly reduced
Spn adherence to A549 cells.
Based on our preliminary data, we hypothesize that “Genetic fusion of CRM197 enhances the memory T-cell
response to Spn antigens, leading to enhanced antibody functionality and protection against Spn colonization
and disease.” This hypothesis will be tested in two structured aims that will establish the role of CRM197 in
enhancing the immunogenic and protective efficacy of Spn antigens, N-PspA and PlyD4. The findings of the
proposed work could lead to a broader utilization of the adjuvant effect of CRM197 in enhancing the immune
response to Spn as well as non-Spn protein antigens, leading to a more robust T-cell dependent immune
response and protective effect.

## Key facts

- **NIH application ID:** 10552114
- **Project number:** 7R21AI151522-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Nadeem Khan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $190,625
- **Award type:** 7
- **Project period:** 2022-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10552114

## Citation

> US National Institutes of Health, RePORTER application 10552114, Utilization of the adjuvant effect of CRM197 protein to develop a trivalent protein-vaccine against Streptococcus pneumoniae infections (7R21AI151522-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10552114. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*