Whether a vaccine would work depends partly on how the immune system responds to it.
Between 2010 and 2015, vaccines have prevented 10 million deaths. Although vaccinations are successful on the population level, individual responses to vaccines are highly variable.
For example, common vaccines for yellow fever, pneumococcal, influenza, hepatitis B, or tuberculosis elicit antibody responses in receivers that may vary by more than 10-fold, sometimes even up to 40- or 100-fold. Why?
In a review published 2019 in Clinical Microbiology Reviews, titled “Factors That Influence the Immune Response to Vaccination,” pediatric infectious disease specialists at the University of Melbourne — Dr. Petra Zimmermann and Prof. Nigel Curtis — outlined the multitude of variables that affect how the immune system responds to a vaccine. These factors include:
Most of these factors are not modifiable, such as age, genetics, maternal factors, etc. But a few are within our control — i.e., modifiable — which will be the focus of this article. Namely, what can we do to increase the odds of generating favorable immune responses to a vaccine, especially when the coronavirus vaccine is just around the corner?
I. Psychological factors
Chronic psychological stress
The review cited numerous studies detailing the link between sustained psychological stress and immune responses to vaccines, which are “mostly negative,” the review authors said.
Five studies showed that the elderly who themselves are caregivers of relatives with dementia did not respond well — such as producing low antibodies and unwanted inflammation — to influenza and pneumococcal vaccines. Another set of six studies found the same applies to non-elderly adults experiencing many stressful life events or high levels of stress, grief, or loneliness.
(Strong antibody responses indicate robust immunological memory, whereas unwanted inflammation produces side effects.)
In contrast, three other studies did not find that chronic psychological stress affected immune reactions to influenza or hepatitis B vaccines in adults. A study even reported that students with higher levels of psychological stress deployed more vigorous antibody responses to the hepatitis B vaccine.
Thus, a stressful life does not always mean poor vaccination outcomes as “antibody responses might also be influenced by coping mechanisms,” the review authors wrote. “For example, individuals who accept the reality of stressful situations have higher antibody responses to HepB [Hepatitis B] vaccination, while individuals who cope by substance use or have high trait negative affect have lower responses.”
Healthy psychological mindset
The more optimistic and social elderly had more excellent antibody and anti-inflammatory responses to the influenza vaccine. Similarly, adults with a fulfilling social support system or marriage mounted more positive immune responses to vaccines for hepatitis B and influenza viruses.
Mindfulness-based stress reduction training for two months, however, did not improve antibody responses to the influenza vaccine compared to no training. The reason could be that two months are too short to bring any concrete impacts on the immune system. Or that social support may be superior in terms of improving vaccination outcomes.
II. Behavioral factors
Runners elicited higher antibody responses to the tetanus vaccine compared to non-runners in an old study. But another study did not find any variations in antibody responses between triathletes and sedentary people vaccinated for diphtheria, tetanus, or pneumococcus.
Other studies found enhanced antibody production to the influenza vaccine in people who exercised before receiving the vaccine. One report discovered that arm circumference in male weightlifters correlated positively with beneficial antiviral immune responses to the influenza vaccine, but a follow-up study could not confirm this result.
Adults over 62 years old who exercised vigorously for >20 minutes at least three times per week had better antibody responses to the influenza vaccine than inactive adults. Yet other interventional studies failed to demonstrate any differences in immune responses to influenza and pneumococcal vaccines between exercise and sedentary groups.
It appears that research on exercise and vaccine immunology has many inconsistencies. Despite that, there is no evidence that exercise hampers vaccine effectiveness. Thus, exercise is either neutral or helpful in boosting desirable immune reactions to vaccines. So, exercise is better than no exercise.
Smokers produced fewer antibodies in response to the hepatitis B vaccine compared to non-smokers in seven studies, the review of Dr. Zimmermann and Prof. Curtis noted. But four studies reported otherwise where researchers did not find that smoking status affected antibody responses to the hepatitis B vaccine.
For influenza vaccines, researchers found that smokers’ antibodies waned quicker than non-smokers. And for the human papillomavirus (HPV) vaccine, antibodies in smokers tend to lose their binding efficacy (to foreign invaders) sooner than non-smokers.
Habitual alcohol consumption does not seem to affect immune responses to hepatitis A and B vaccines in a few studies, the review noted. But, a study in 1993 revealed that alcoholics had lower antibody responses to the pneumococcal vaccine than non-alcoholics. Other than these, data on how alcohol moderates vaccination effectiveness is limited.
Shortened sleep around the week of vaccination for hepatitis A and B and influenza viruses led to weaker antibody responses. The opposite is also true with those with good quality sleep around the time of hepatitis A vaccination where they generated desirable immune reactions.
Intriguingly, people with moderate-to-severe obstructive sleep apnea mounted the same degree of immune reaction to the influenza vaccine as the healthy controls, even though they had sleep deprivation.
Perhaps only sudden short-term (not chronic or long-term) sleep loss around the period of vaccination would impede its effectiveness. Or that sleep is only a variable that affects the outcomes of certain types of vaccines. Anyhow, ample sleep quality will not impede vaccine effectiveness but may help instead.
III. Nutritional factors
Body mass index (BMI)
Nearly 20 studies, the research review cited, found that increasing BMI correlated with weaker antibody responses to hepatitis A and B vaccines.
For the influenza vaccine, higher BMI correlated with higher antibody production, but the antibodies also waned quicker 12 months later. This study also showed that those with obesity did not mount proper T-cell responses to the influenza vaccine.
(B-cells, that make antibodies, and T-cells make up the adaptive immune system that is responsible for the targeted killing of pathogens and the subsequent creation of immunological memory.)
Likewise, low BMI or undereating impedes immunization. A plethora of studies, the review summarized, reported that the immune system of malnourished children failed to respond competently to vaccines for hepatitis B, measles, meningococcus, poliovirus, pertussis, Salmonella typhi, and tetanus.
Micronutrients (vitamins A, D, and E and zinc)
Of all micronutrients, the review pointed out, vitamin D is the most examined with over ten studies (mostly on influenza vaccines). But there is no explicit agreement if vitamin D status or supplementation enhances vaccine efficacy. Similarly, eight studies on vitamin A in children found either positive or neutral effects on vaccination outcomes for measles, diphtheria, and tetanus.
Only one study investigated vitamin E and zinc in the elderly who are not vitamin deficient, where they observed no associations in regards to influenza vaccinations.
A positive note is there is no evidence of adequate micronutrition sabotaging vaccination efficacy. Akin to exercise, sleep, and other factors, it is safe to assume that sufficient micronutrients are better than insufficient when undergoing vaccinations.
This sort of research on factors affecting immunization primarily analyzes antibodies. “Most studies investigating vaccine responses quantify antibodies,” the review authors admitted. “However, vaccine responses are far more complex than just measurable antibody concentrations.”
One of the key lessons from Covid-19 is that antibodies made by B-cells fade over time. And that T-cells play an equally, if not more, important role in immunological memory. T-cells boost the activities of other types of immune cells (including B-cells) while also possessing the ability to kill cells infected with pathogens. But, as T-cells’ activities are much more diverse, testing them is more complicated as well.
Therefore, declining or low antibody levels in some of the studies discussed above does not necessarily imply the absence of immunity. Regardless, strong antibody responses are always welcomed as they do signify immunity.
So, what can be done to maximize the odds of successful vaccination? The basic healthy habits help, especially during the week before and after vaccination when the immune system needs to stay in top shape to generate the desirable immune responses and memory.
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