# Wild-type allele found in varicella vaccine virus during severe herpes zoster

> **NIH NIH R21** · UNIVERSITY OF IOWA · 2020 · $226,845

## Abstract

This grant proposal is submitted under PA-18-872 Research to advance vaccine safety. The impetus for this
R21 grant proposal is a recent report from this lab in the Journal of Child Neurology 2019. The title of the
article: Severe herpes zoster following varicella vaccination of immunocompetent young children. The
hypothesis for this proposal is that VZV ORF0 is a major determinant of attenuation in the live varicella vaccine
vOka; further, a variant of the current vaccine product that contains the wild-type ORF0 allele rather than the
attenuated ORF0 allele is more likely to reactivate as severe herpes zoster. My lab and a Canadian lab made a
critical discovery about VZV attenuation after we sequenced the entire genome of the well-known Ellen lab
strain. We had previously shown, using the Arvin lab’s SCID mouse model, that the Ellen strain was even
more attenuated than the Oka vaccine strain. When we compared the complete sequence of Ellen and vOka,
we made a completely unpredictable discovery. The two strains had common SNPs in IE62 gene, as
expected. What was not expected was the discovery that the Ellen lab strain (a wild type strain isolated in
Georgia in the 1960s) had a vaccine-type ORF0 gene. Unbeknownst to VZV researchers, therefore, the Ellen
strain had acquired polymorphisms in both IE62 (ORF62) and ORF0 that were extremely similar to the vaccine
strain. The goal of the R21 grant is to initiate studies to define ORF0 as an important determinant of
attenuation in the VZV vaccine. Essentially, therefore, this grant proposes that the virologists who first made
the live varicella vaccine in the 1970’s omitted a step in the late design of the vaccine, which allowed a more
virulent variant to be included in the final vaccine product. The research plan includes two specific aims and
also includes two consultants. The importance of this research has vaccine safety relevance. There have
been thousands of reports of adverse event after varicella vaccination, including death from disseminated
vaccine virus infection. Since the original stocks of vaccine virus were never cloned by the Takahashi lab in
Osaka, the current commercial vaccine product contains a variant with wild-type ORF0 allele. We suggest that
the vaccine subspecies or variant with wild-type ORF0 may be causing many of the severe side effects
following varicella vaccination.

## Key facts

- **NIH application ID:** 10038935
- **Project number:** 1R21AI153817-01
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Charles F. Grose
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $226,845
- **Award type:** 1
- **Project period:** 2020-05-21 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10038935

## Citation

> US National Institutes of Health, RePORTER application 10038935, Wild-type allele found in varicella vaccine virus during severe herpes zoster (1R21AI153817-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10038935. Licensed CC0.

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