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Scitech | A movement toward individualized vaccines

X chromosomes kick your immune system into gear

The colder season seems to be synonymous with vaccine season, year after year; as we layer up for winter, recommendations for flu shots seem to pop up everywhere. Despite this apparent correlation, vaccines are not, in fact, seasonal – they are offered year-round for a plethora of diseases. In order to stay as healthy as possible, it is important to understand vaccines, and it is not as simple as you may think: the effects of vaccines vary based on the assigned sex of each respective recipient.

A vaccine is a biological substance that either closely resembles a pathogen or is a weakened, attenuated form of a microbe. This substance is introduced to the body, traditionally with a needle, leading to an attack on the vaccine by the immune system. The reason this works is because memory B cells in the immune system keep a record of this administered “infection.” Should the actual microorganism, be it a bacteria or virus, infect that person, their body is well equipped and ready to deal with the threat. Vaccines that work in this way are called prophylactic vaccines, intended for preventative measures against future infections. A second type of vaccine, called a therapeutic vaccine, is used to treat diseases currently affecting the body. No matter the type, vaccines work in tandem with the immune system to rid the body of dangerous disease-causing pathogens.

That the effects of vaccinations differ between sexes was first discovered in a study at Johns Hopkins University in late 2014. Although sex is assigned at birth based on visible characteristics that are a result of the genetic makeup of a person, there are also immunological, hormonal, and genetic determinants when it comes to the assignment. Immunologically, people who are assigned female at birth, who commonly have two X chromosomes, have a higher number of cytokines – cells that act as the “weapons” of the immune system. Cytokines carry out immunological functions against pathogens and allow the body to recover. Hormonal differences in people also play a role. Estradiol, progesterone, and testosterone are the dominant hormones found in people assigned male at birth, who commonly have XY chromosomes, and negatively affect the function of immune cells. It has been found that testosterone suppresses pro-inflammatory cytokine secretion by macrophages, an important type of immune cell that mediates the elimination of pathogens. In contrast, estrogen is dominant in assigned females and interacts with immune cells through estrogen receptors on cell surfaces to enhance cell function.

Many immune-related genes such as interleukins, cytokines, and receptors are located on the X chromosome, leading to the final point of genetic determinants of vaccine proficiency. Therefore, there are less genes in assigned males that are important for immune responses. This double dosage of the X chromosome explains why vaccinations will have a greater variation of effects for those assigned female at birth, both positively and negatively. The biological characteristics of those with XX chromosomes cause them to have nearly twice the antibody response, and stronger cell-mediated immunity following the vaccination. However, they also experience worse reactions following the injection, such as fever, pain and inflammation, when compared to those with XY chromosomes.

Vaccines are not, in fact, seasonal – they are offered year-round for a plethora of diseases.

The findings of the John Hopkins study suggest that the design of vaccines should be strategically sex-specific to reduce side effects in assigned females and increase immune responses in assigned males by altering dosages to optimize its effects. These findings also raise important questions about the effects of vaccinations on intersex or trans individuals, who may have had surgery and or hormonal treatments. This could raise problems when measuring doses based on sex, when the medically recorded assigned sex of the person may not reflect the hormonal or physical changes after birth. It would be very difficult to predict the optimal dosage of various vaccines to achieve high levels of immunity and low levels of adverse side effects for each case, trans and interex people especially. It is especially tricky to determine the effects of immunological and hormonal differences in these individuals after they have undergone changes to their body. Observational studies of side effects are also as or more difficult to observe for intersex and trans individuals, and pose as another hurdle in optimizing individualized vaccinations. Further studies are essential for the safety of vaccinations and the health of all individuals. In order to be most effective, doctors should take into account an individualized approach for vaccine administration and research.

The standards of administered drugs and vaccinations are rapidly changing for the better, and individualized medicine is becoming a promising field in healthcare and therapeutics. Soon, a quick trip to your local drugstore to get a universal flu shot won’t be so simple.


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