# A Nanoparticle-Based Multivalent Rotavirus Vaccine

> **NIH NIH R56** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $626,446

## Abstract

Rotavirus (RV) causes severe diarrhea in children with significant morbidity and mortality. While the current live
oral RV vaccines are highly effective in developed nations, their efficacies are impaired in developing countries,
where most RV morbidity and mortality remain and thus where RV vaccines are needed the most. Factors
leading to the impaired efficacies include microbiota dysbiosis, concurrent uses of poliovirus and other oral
vaccines, enterovirus infections, and malnutrition that impact intestinal conditions and thus the efficacies of the
oral RV vaccines. As a result, parenteral RV vaccine approaches are called to improve the efficacy in the
developing countries. To this end, we have developed an innovative, nanoparticle-based S60-VP8* RV vaccine
that would meet such calls. The recombinant, nonreplicating nature of our vaccine and its parenteral delivery
method will also reduce vaccine production cost and prevent intussusception risk of the live RV vaccines for
better safety and cost-effectiveness. The bioengineered S60-VP8* nanoparticle is self-assembled, easily
produced, highly stable, and extremely immunogenic, and therefore, an excellent RV vaccine candidate. Each
S60-VP8* nanoparticle contains a 60-valent norovirus inner shell and 60 surface-displayed RV VP8* antigens.
The viral receptor-binding VP8* is an ideal RV vaccine target, because antibodies elicited by nature RV infections
are mostly VP8*-specific and vast majority of VP8*-directed antibodies neutralized RV infections. As a proof of
concept, we have shown the high immunogenicity, neutralization, and protection of the S60-VP8* nanoparticle
displaying the predominant P[8] RV VP8* in mouse model. In this application we will produce a cocktail S60-VP8*
nanoparticle vaccine displaying RV VP8*s of the globally predominant P[8], P[4], P[6], and P[11] RVs and define
its safety, immunogenicity, and protective efficacy using the mouse and the highly relevant gnotobiotic (Gn) pig
models. This is the first nanoparticle-based cocktail RV vaccine covering all four predominant P type RVs and
therefore will provide a broad protection against RV infections in both developed and developing nations. The
outcomes from both small and large animal models will prove the usefulness and thus facilitate future clinical
trials of our S60-VP8* nanoparticle vaccine. Two major lines of experiments will be performed in this application.
First, we will produce the cocktail S60-VP8* nanoparticle vaccine covering the four predominant RV P types
(P[8]/P[4]/P[6]/P[11]) and evaluate the cross-P type immune responses, neutralizations and protections, as well
as delineate the immune mechanisms of the cocktail vaccine in mice. Second, we will determine the safety,
cross-P type immunogenicity, and broad neutralization/protection of the cocktail nanoparticle vaccine compared
with the currently implemented live RV vaccines in the Gn pig human RV challenge model. Mechanistic study
will also be performed to unders...

## Key facts

- **NIH application ID:** 10206373
- **Project number:** 1R56AI148426-01A1
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Ming Tan
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $626,446
- **Award type:** 1
- **Project period:** 2020-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10206373

## Citation

> US National Institutes of Health, RePORTER application 10206373, A Nanoparticle-Based Multivalent Rotavirus Vaccine (1R56AI148426-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10206373. Licensed CC0.

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