Conclusion
Varicella vaccines can rarely cause herpes zoster due to vaccine-strain viral reactivation. Other vaccines currently routinely recommended to the general population in the U.S.* do not cause vaccine-strain viral reactivation.
Epidemiological Evidence
The 2012 report by the Institute of Medicine (IOM), now called the National Academy of Medicine (NAM), described one study assessing varicella vaccination with vaccine-strain viral reactivation 1; however, it did not provide convincing evidence due to a lack of validity and precision 2.
One large randomized controlled trial published since the 2012 IOM report and conducted in ten European countries found one unconfirmed case of herpes zoster infection and one papular rash out of 4976 recipients of either the MMR vaccine PriorixTM and the varicella vaccine Varilrix® or the combination MMRV vaccine Priorix-Tetra®, all vaccines not used in the U.S. Both of these serious adverse events ** were reported as recovered or resolved 3.
One Israeli study found no association between Comirnaty, the Pfizer-BioNTech COVID-19 vaccine, and herpes zoster 4; however, another larger Israeli study found an excess risk of 15.8 cases of herpes zoster per 100,000 persons vaccinated with Comirnaty 5, though this is not due to vaccine-strain viral reactivation.
Proposed Biological Mechanism
Varicella vaccines are live attenuated viral vaccines, and are therefore able to replicate in the body. Generalized rash is reported in 4-6% of recipients. Systemic reactions are uncommon but possible. Mild zoster illness (shingles) resulting from a latent infection with varicella vaccine virus has been reported. Some cases of herpes zoster after vaccination are due to reactivation of wild type varicella virus from a prior (usually unrecognized) primary varicella infection 6. Immunodeficiency is a contraindication for most live vaccines, including varicella vaccine. For more information, see the Varicella summary.
The 2012 IOM report described cases of vaccine-strain viral reactivation after varicella vaccination 6-25, and concluded that these cases together presented strong mechanistic evidence supporting an association 2. A laboratory-documented case of herpes zoster caused by the vaccine-strain varicella zoster virus in an immunocompetent recipient of zoster vaccine was reported in 2014 26. In immunodeficient persons, vaccine-strain viral reactivation can result in meningitis 6,11,23-25 or encephalitis 13,22.
* These conclusions do not necessarily consider vaccines recommended only for special populations in the United States such as Yellow Fever vaccine (international travelers) or Smallpox vaccine (military personnel), or vaccines no longer recommended to the public such as the Janssen (J&J) COVID-19 vaccine.
[**] A serious adverse event is defined by the Food and Drug Administration (FDA) as resulting “in any of the following outcomes: Death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.” This definition is found in Title 21, §312.32 of the Electronic Code of Federal Regulations.
References
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