# LIVE VIRUS VACCINES AS DOMINANT NEGATIVE MUTANTS

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 1991 · $161,695

## Abstract

The research proposed has two main goals: first, to test the ability of
live virus vaccines used for influenza, poliomyelitis, measles, mumps, and
rubella to act as dominant-negative mutants; and second, to examine the
mechanism of this dominance where it is found to occur. The ability to
inhibit the growth of wild-type virus in mixed infections is a desirable
trait for any live virus vaccine. This phenotype could permit the vaccine
strain to block the growth of any wild-type revertants that arise during
the immunization process. Dominance may also afford protection to
superinfection with an external source of wild-type virus during
immunization or modify a developing infection.

Cell culture and animal model systems will be employed to examine the
effects of coinfection with the live virus vaccines on the growth of
wild-type virus. The relative yield of the two viruses will be analyzed by
a variety of quantitative and qualitative techniques. Preliminary studies
have established that coinfection with the cold-adapted candidate vaccine
for influenza A inhibits the growth of wild-type virus by as much as three
orders of magnitude. Through the use of single gene reassortants, the
identity of the vaccine virus gene(s) responsible for this interference
will be determined. In addition, experiments will be performed to establish
the point in the growth cycle at which the interference occurs. Similar
studies are planned with the other live virus vaccines that are found to
interfere.

It is important to note that regardless of whether all of the presently
available live virus vaccines possess the dominance characteristic; this is
a trait that a live virus vaccine should have. This may be of particular
importance in the case of poliomyelitis, where vaccine failure due to
reversion to neurovirulence remains a significant public health problem. If
the current vaccines are not dominant, identification of dominant-negative
lesions in other mutant polioviruses may permit the genetic engineering of
vaccine viruses which possess this added safety factor.

## Key facts

- **NIH application ID:** 3124290
- **Project number:** 5R01AI006264-27
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **SAM.gov UEI:** MKAGLD59JRL1
- **Principal Investigator:** JULIUS S YOUNGNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $161,695
- **Award type:** 5
- **Project period:** 1974-09-01 → 1995-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3124290

## Citation

> US National Institutes of Health, RePORTER application 3124290, LIVE VIRUS VACCINES AS DOMINANT NEGATIVE MUTANTS (5R01AI006264-27). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3124290. Licensed CC0.

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