Inappropriate Citation of Vaccine Article

To the Editor—We wish to call attention to an unfortunate misuse of our 2008 article published in The Journal of Infectious Diseases [1]. Our article is being used by some to support medical exemptions to vaccination in children with a common genetic polymorphism (C677T) in the gene encoding methylenetetrahydrofolate reductase (MTHFR), particularly to measles vaccine. The citation of this exploratory report, which addressed a unique set of phase 1 studies of a candidate smallpox vaccine, should not constitute an exemption from formal vaccination recommendations issued by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices. There is no published evidence to suggest that the likelihood of an adverse reaction to one vaccine implies that an individual is expected to have a reaction to other unrelated vaccines. In this regard, results observed for a vaccine that is not approved by the Food and Drug Administration (FDA) and that targets an infectious pathogen against which people are no longer vaccinated do not have implications for the risk of adverse events due to vaccines approved by the FDA for use against other infectious pathogens.

The limitations of our study in assessing adverse reactions to smallpox vaccine and other vaccines, particularly measles vaccine, are several. The study was a small, underpowered, exploratory, candidate gene study conducted >15 years ago in a special population—participants in 2 small phase 1 studies of smallpox vaccines. This article does not meet the standards for establishing a robust genetic association. It is most likely that the reported relation to a common variant (ie, C677T) in MTHFR is due to chance. In fact, the article clearly states that “[i]t is possible that our findings could be due to chance” and “follow-up replication and functional studies are needed to establish the plausibility of the association” [1]. The findings presented have not been replicated in additional settings involving individuals receiving a smallpox vaccine or in any other setting testing for genetic modifiers of vaccine response or adverse events. In this regard, we wish to emphasize that this use of MTHFR polymorphisms to support medical exemptions to vaccination in children represents an inappropriate and unsubstantiated use of direct-to-consumer genetic testing. The policy statement of the American Academy of Pediatrics and the American College of Medical Geneticists and Genomics strongly discourages the use of direct-to-consumer testing, because of the risk of inaccurate interpretation of findings and the risk of a potentially harmful intervention (eg, avoidance of a medically indicated vaccine) [2].

In conclusion, the invalid interpretation that the presence of the MTHFR variant is an acceptable reason for a vaccine exemption is not based on the precepts of replication of study findings and rigorous clinical testing. It is unfortunate that the loose application of our exploratory report has been misinterpreted and used to inappropriately justify exemption of children from receiving medically indicated vaccines.

Potential conflicts of interest. J. E. C. has been a consultant to Valneva, has received research funding from NIH, DARPA, DTRA, the Bill and Melinda Gates Foundation, Moderna Therapeutics, and Takeda Vaccines, has been on the scientific advisory boards for Compuvax and Meissa Vaccines, and is Founder of IDBiologics. K. M. E. has been a consultant to Moderna Therapeutics, Roche, Sanofi, and X4 Pharmaceuticals, has received research funding from the NIH and CDC, and has been on advisory boards for Bionet, GSK, and Sequiras. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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