# Novel vita-vaccine formula combines safety of dead and efficacy of live vaccines

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $419,267

## Abstract

PROPOSAL SUMMARY
Live attenuated vaccines have proven to be the most efficient human vaccines for many serious infectious
diseases. When compared to their dead counterparts, live vaccines induce superior immune protection and
lasting memory. But despite the efficacy of live vaccines, concerns over their safety have led to vaccine refusal
by some and withholding their administration to the very young, the elderly and immunocompromised.
Preservation and delivery of live vaccines especially to impoverished areas in developing countries is difficult
and expensive. Understanding the molecular basis for the efficacy of live vaccines is significant because it
would enable targeting of the relevant immune pathways that induce optimal and long-lasting protective
immunity. Importantly, it would set the stage for the development of vaccines that are safe and afford the same
protection as live vaccines, alleviating public fears and increasing the segment of the population that is
vaccinated. We began our work eight years ago with the hypothesis that innate immune cells sense microbial
viability as a distinct set of pathogen associated molecular patterns (PAMPs), and we identified bacterial
messenger RNA (mRNA) as a vita-PAMP that signifies bacterial viability and mobilizes a tailored immune
response not warranted for dead microorganisms. The Toll-like receptor (TLR) signaling adaptor TRIF plays a
central role here upstream of inflammatory type I interferon and NLRP3 inflammasome pathways. Adding
bacterial mRNA to dead bacteria recapitulates these innate responses, and supplementing a dead vaccine with
bacterial mRNA (what we call a vita-vaccine) augments its performance in mice. A vita-vaccine performed
similarly to a live vaccine in uniquely eliciting a follicular T helper cell response (that helps B cells), germinal
center formation, and B cell isotype class switching, all in a TRIF-dependent manner. These studies provide
strong evidence that vita-vaccine versions of existing vaccines could represent a significant advance in being
able to combine the efficacy of live vaccines with the safety of dead vaccines. The three overlapping areas we
will investigate in this project are:
1. We will determine how adaptive immunity elicited by the supplementation of a dead bacterial vaccine with
the vita-PAMP bacterial mRNA compares to that elicited by PAMPs such as bacterial lipopeptides and others.
2. We will investigate how bacterial mRNA impacts the performance of subunit vaccines. We will test vita-
vaccine versions of the licensed anthrax subunit vaccine and Influenza A virus monovalent subunit vaccine.
3. We will test a vita-vaccine version of a trivalent inactivated Influenza virus vaccine and compare it to the
live attenuated influenza vaccine.
 The completion of these studies should provide sufficient experimental evidence to warrant the use of
bacterial mRNAs as superior vita-adjuvants that restore the signatures of microbial viability to dead vaccines
and i...

## Key facts

- **NIH application ID:** 9994814
- **Project number:** 5R01AI127658-06
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Julie Magarian Blander
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $419,267
- **Award type:** 5
- **Project period:** 2016-09-23 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994814

## Citation

> US National Institutes of Health, RePORTER application 9994814, Novel vita-vaccine formula combines safety of dead and efficacy of live vaccines (5R01AI127658-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9994814. Licensed CC0.

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