# Physiological and immunological responses to measles vaccine

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $661,557

## Abstract

Summary
Measles remains one of the most important causes of child morbidity and mortality worldwide. Studies of
measles in children and in a well-characterized rhesus macaque model have shown that clearance of wild type
(WT) measles virus (MeV) RNA is ongoing for many months after clearance of infectious virus with persistence
in peripheral blood mononuclear cells and lymphoid tissues. RNA persistence is accompanied by ongoing
immune stimulation with continued production of MeV-specific plasmablasts, antibody (Ab) maturation and
multiple waves of functionally distinct T cells. These immune responses result in lifelong immunity to measles,
but comparable data are not available for the live attenuated MeV vaccine. The MeV vaccine was developed
empirically by attenuation of a WT MeV isolate by passage in chicken cells. The resultant live attenuated
vaccine was licensed in 1963 and has been remarkably safe and successful although delivery by injection
creates hurdles to sustained high coverage that might be alleviated with respiratory delivery. Its safety record,
combined with advances in reverse genetics for negative strand viruses, have led to development of
recombinant versions as vectors for immunization against other infections and as oncolytic agents for a variety
of tumors. However, limited understanding of fundamental aspects of MeV vaccine virus in vivo biology hinders
development. For instance, there is little knowledge of where the vaccine virus replicates, the mechanism(s) of
attenuation of virulence or how the immune responses induced differ from those induced by WT infection
except to note that antibody titers are lower and protection is less durable. We hypothesize that a central
difference between infection with vaccine and WT strains is the ability to replicate and persist in lymphoid
tissues. This proposal will address this knowledge gap by: 1) Identifying the target cell(s) in which vaccine virus
replicates less well than WT virus. We hypothesize that attenuated replication is cell type-specific and that
vaccine strains of MeV replicate well in myeloid, endothelial and epithelial cells, but poorly in lymphoid cells. 2)
Identifying the viral determinants of inefficient MeV vaccine virus replication. We hypothesize that the
hemagglutinin (H) and matrix (M) proteins are the primary determinants of inefficient replication in lymphocytes
through effects on TLR2 signaling, virus assembly and release and will test the hypothesis by constructing
recombinant strains of EZ vaccine that will tested for replication in lymphocytes. 3) Determining the in vivo sites
of vaccine virus replication and dynamics of viral RNA clearance in rhesus macaques. We hypothesize that
vaccine strains of MeV do not spread efficiently from lymphoid sites of infection and that both infectious virus
and viral RNA are cleared quickly. 4) Identifying differences in the CD4+ T cell and Ab responses to infection
with vaccine and WT MeV. We hypothesize that vaccine strai...

## Key facts

- **NIH application ID:** 9984948
- **Project number:** 5R01AI131228-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Diane E Griffin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $661,557
- **Award type:** 5
- **Project period:** 2018-08-06 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984948

## Citation

> US National Institutes of Health, RePORTER application 9984948, Physiological and immunological responses to measles vaccine (5R01AI131228-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984948. Licensed CC0.

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