Vaccines and Genomics

October 29, 2015

This post launches a new series from our Genomic Uses in Infectious Diseases and Epidemics (GUIDE) Project team.


The issues surrounding the use of genomics in infectious disease prevention, treatment, and outbreak control are complex and ever-changing. There are many important perspectives to be heard; and opinions will vary, even within our own research team.


One of the aims of this project is to determine how the public perceives the risks and benefits of genomic applications to infectious diseases, and to begin to understand the role of media in the conversation surrounding genomics and infectious disease.


To that end, we will be sharing some of our own perspectives on this topic in a series of blog posts, with which we hope to inspire open discussion.


We believe it is important for both the academic community and the public to start thinking about the many potential ethical, legal and social implications of genomic applications in the context of communicable diseases.


Weighing the potential benefits versus harms of genetic testing for adverse reactions to vaccination


Aside from the usual reminders of the importance of vaccination (Get your flu shot!), this year, in particular, a number of events have launched the discussion of vaccines back into the public’s consciousness: the measles outbreak in Disneyland, California’s ruling mandating vaccination for all schoolchildren except in the case of a medical exemption, and, most recently, the Republic presidential debate, in which a candidate asserted a link between vaccines and autism, a fallacious connection that was originally publicized as a result of falsified data and has been scientifically refuted many times over.


Issues related to vaccination and vaccine policy can be controversial, but these issues may become even more complicated in the future if and when scientific advances reveal genetic contributions to how our bodies respond to infectious disease and vaccines.


There is increasing evidence that our unique genetic code can contribute in some cases to our varying susceptibility to infectious disease (see, for example, this recent genetic association with risk of severe flu), and to the way our immune system responds to treatments or preventive interventions such as vaccines.


With vaccine safety and vaccine policy on our nation’s mind, we here outline some thoughts about potential genomics applications to clinical and public health decision making around vaccines, and discuss the ethical and social implications of these uses. We invite your thoughts and reactions.


Michelle Huckaby Lewis, MD, JD


The measles outbreak earlier this year demonstrates that parental refusal to allow their children to be vaccinated against infectious diseases is a growing public health problem in the United States. There is a strong body of evidence that shows that vaccines are very safe, but concerns about serious side effects are given as the most common reason for parental refusal of vaccines despite the fact that serious adverse reactions are extremely rare.


There is some evidence to suggest that genes contribute to differences in people’s immune responses to certain vaccines and to variation in physiological reactions (such as fever) following vaccination. In the future, it might be possible to use genetic testing to identify individuals who are at increased risk of a serious adverse reaction to a particular vaccine. The potential benefits of using this type of genetic testing would be to identify those rare individuals at increased risk of a specific adverse event following vaccination, to allay fears of parents whose children do not have that particular risk variant, and to increase public confidence in vaccine safety.


If this type of genetic testing becomes possible, before being integrated into clinical care, it would be critical to assess how this information would be utilized by the medical community and the public. In other words, before implementing any genetic screening of this sort in clinical care or public health policy, it would be important to ascertain whether the information would allay parental fears about possible side effects and therefore increase immunization rates and confidence in vaccines or whether it might be misunderstood by concerned parents leading to less confidence and use of vaccines.


Daniel Salmon, PhD, MPH


Advances in immunology and genomics afford the opportunity to better understand variability in how people respond to vaccines. Some people under-respond and don’t have a sufficient immunological response to be protected if exposed to the disease.  Others might over-respond, experiencing an adverse reaction to the vaccine. Adverse events caused by vaccines are either minor, such as a fever or sore arm, or very rare.


Many would agree that the common adverse vaccine reactions, such as fever or sore arm, are too minor to warrant genetic screening to avoid. Some argue that the serious adverse reactions are so rare that it shouldn’t be a scientific priority to figure out the risk factors, as scientific research dollars could be better spent studying health problems that have an impact on a greater number of people. Furthermore, some say even if we were to identify a genetic risk factor, the events are so rare that it wouldn’t be cost effective to screen for these individuals. Some have also raised concerns that this sort of research could be misunderstood by parents and lead to decreased public confidence in vaccines.


These are all important points to consider; however, none of them should interfere with the pursuit of the safest possible vaccines or vaccination strategies. Understanding what role individual risk factors, such as genes, play in common minor reactions may not lead to forgoing vaccination among those people with the relevant genetic marker. In most cases, the benefits of the vaccines would still outweigh the risks. Yet gaining this scientific knowledge might lead to other important practical solutions, perhaps in how new vaccines are developed. Similarly, while it may not be feasible today to screen large populations for serious but very rare adverse reactions—even if the genetic risk factor were known and a screening test available—this knowledge could lead to other important discoveries that could improve health and reduce adverse events. Screening that may be cost prohibitive today might become routine in the not-too-distant future.


Understanding the biological mechanisms for adverse vaccine reactions, whether generally mild and common or serious but rare, should be a scientific priority. Given the near universal exposure to vaccines and the need to maintain high levels of public confidence, we should vigorously pursue research to identify why vaccines don’t always work as we would want. We also must understand how to communicate the science with parents, so that the pursuit of science builds rather than detracts from public confidence.


Rachel Dvoskin, PhD, and Gail Geller, ScD, MHS


Any disclosure of genetic risk factors for adverse reactions to a vaccine—in either a clinical or public health setting—would require the most clear and careful communication possible. In most cases, any given genetic risk factor (for example, for common diseases and traits such as heart disease, cancer, obesity, or alcoholism) is only one of many risk factors for a negative health outcome and contributes a relatively small amount to the population’s variation in that outcome. In other words, genes are rarely 100% (or even 10%) predictive of an illness or adverse reaction in a particular individual.


Consider a hypothetical example: a genetic mutation that shows up in 5% of the population might mean that, on average, those 5% are more likely than the other 95% of the population to have an adverse event following vaccination; however, the likelihood of such an event might still be extremely small. As another example, if 1% of young children (or 1 out of 100) typically have elevated fever after receiving a vaccine, and children with a particular genetic mutation have double the risk of fever, that means those children still only have a 2% risk of fever after vaccination.


This type of information might be something that parents want to know, and it might warrant disclosure, but the importance of how it is communicated cannot be overstated. Health care providers sharing this type of information would have an ethical obligation to try to ensure that the parent, or patient, understands the probabilistic nature of genetic risk factors, as well as the health risks of contracting a particular disease if they are not vaccinated.


More work needs to be done to learn the most effective ways of communicating with parents not only about risk but about vaccine safety. Furthermore, it is important to communicate the benefits of vaccination not only for one’s own health but for the health of the community. Better and more widespread understanding of the concept—and importance—of herd immunity should help to inform personal decisions about vaccination.


The only responsible way to think about disclosing such genetic information would be in a setting of increased global understanding of genetics, of the probabilistic nature of genetic risk factors, and of what we do and do not know about the genetic underpinnings of the immune response. This will not be achieved without improved genetic education among lay people and health care providers alike.

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Daniel Salmon
Gail Geller
GUIDE Project
Michelle Lewis
Rachel Dvoskin

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