US Pharm. 2023;48(4):55-58.

Good Night’s Sleep Could Boost Vaccine Response

We all know how important sleep is for mental health, but a meta-analysis published recently in the journal Current Biology found that getting good shut-eye also helps our immune system respond to vaccination. The authors found that people who slept fewer than 6 hours per night produced significantly fewer antibodies than people who slept 7 hours or longer, and the deficit was equivalent to 2 months of antibody waning.

“Good sleep not only amplifies but may also extend the duration of protection of the vaccine,” said senior author Eve Van Cauter, professor emeritus at the University of Chicago, who, along with lead author Karine Spiegel at the French National Institute of Health and Medicine, published a landmark study on the effects of sleep on vaccination in 2002.

When the COVID-19 pandemic hit and mass vaccination became an international priority, Drs. Spiegel and Van Cauter set out to summarize our current knowledge about the effect of sleep duration on vaccine response.

To do this, they combed the literature and then combined and reanalyzed the results of seven studies that vaccinated for viral infections (influenza and hepatitis A and B). In their analysis, the team compared the antibody response for individuals who slept a “normal” amount (7-9 hours, as per the National Sleep Foundation’s recommendation for healthy adults) with “short sleepers” who slept fewer than 6 hours per night. They compared the effect for men versus women and adults over age 65 years versus younger adults.

Overall, they found strong evidence that sleeping fewer than 6 hours per night reduces the immune response to vaccination. When they analyzed men and women separately, though, the result was only significant in men, and the effect of sleep duration on antibody production was much more variable in women. This difference is probably due to fluctuating sex hormone levels in women, the authors say.

“We know from immunology studies that sex hormones influence the immune system,” said Dr. Spiegel. “In women, immunity is influenced by the state of the menstrual cycle, the use of contraceptives, and by menopause and postmenopausal status, but unfortunately, none of the studies that we summarized had any data about sex hormone levels.”

The negative effect of insufficient sleep on antibody levels was also greater for adults aged 18 to 60 years compared with people over age 65 years. This was not surprising because older adults tend to sleep less in general; going from 7 hours of sleep per night to fewer than 6 hours is not as big of a change as going from 8 hours to fewer than 6 per night.

Some of the studies measured sleep duration directly, either via motion-detecting wristwatches or in a sleep laboratory, while others relied on self-reported sleep duration. In both cases, short sleep duration was associated with lower levels of antibodies, but the effect was stronger for the studies that used objective measures of sleep, likely because people are notoriously bad at estimating the amount of sleep they have had.

Knowing that sleep duration impacts vaccination might give people some degree of control over their immunity, the authors said. “When you see the variability in protection provided by the COVID-19 vaccines—people who have preexisting conditions are less protected, men are less protected than women, and obese people are less protected than people who don’t have obesity. Those are all factors that an individual person has no control over, but you can modify your sleep,” said Dr. Van Cauter.

However, there’s a lot more to be known about sleep and vaccination, the authors said. “We need to understand the sex differences, which days around the time of vaccination are most important, and exactly how much sleep is needed so that we can give guidance to people,” said Dr. Spiegel. “We are going to be vaccinating millions and millions of people in the next few years, and this is an aspect that can help maximize protection.”

T Cells That Protect Against Deadly Pneumococcal Disease Discovered

A new study by University of Liverpool researchers reveals how resistance to bacteremic pneumonia is provided by a unique subset of lung T regulatory cells.

Streptococcus pneumoniae (the pneumococcus) is the leading cause of community-acquired pneumonia, with a significant proportion of cases developing bloodstream infections. Such cases of bacteremic pneumonia are associated with a high fatality rate, ranging from 20% in young adults to approximately 60% in the elderly, despite the broad application of antibiotic treatment and the availability of effective vaccines. The reasons why certain individuals are more susceptible to invasive pneumococcal disease and others are more resistant have been one of the central unanswered questions of pneumococcal research for decades.

The Bacterial Pathogenesis and Immunity Group, led by Aras Kadioglu at the University of Liverpool, U.K., has discovered a subset of white blood cells in mice that confer resistance to bacteremic pneumonia. These cells have been identified as TNFR2 expressing regulatory T cells (Tregs), and they have been shown to be critical in the maintenance and control of frontline host immune responses when pneumococci infect the lungs. When these special subset of Tregs are functionally impaired or absent, the immune response to infection becomes dysregulated with excessive and uncontrolled inflammation, which leads to tissue damage, allowing bacteria to spread through disrupted lung tissue barriers into the bloodstream, causing a severe and deadly sepsis.

The first author of the study in Cell Reports, Rong Xu, said, “Pneumococcal infection remains a major killer globally, despite the successful introduction of pneumococcal vaccine immunization programs. Elucidating the mechanisms of how resistance to infection may develop in high-risk groups offers a great opportunity for us to develop targeted novel therapies.”

The study lead, Dr. Kadioglu, added: “Our findings show that TNFR2-expressing Treg cells are absolutely essential in controlling inflammation in the lungs and preventing the translocation of pneumococci from lung to blood, thereby providing resistance to invasive disease. In susceptible hosts, however, these cells are either functionally impaired or absent, which predisposes them to the development of sepsis. This is a significant finding, which opens the door to potential new therapies which may target and modulate this subset of Tregs to prevent and treat severe invasive pneumococcal diseases.”

COVID-19’s Persistent Effects on Adolescent Mental Health

The COVID-19 pandemic has had a long-lasting impact on adolescent mental health and substance use, according to a new population-based study of  survey responses from a nationwide sample of over 64,000 13- to 18-year-old North American and Icelandic adolescents assessed prior to and up to 2 years into the pandemic. The study was conducted by faculty at Columbia University Teachers College and Mailman School of Public Health and a team of Icelandic and other North American clinical, behavioral, and social scientists. The findings were published in The Lancet Child & Adolescent Health.

This same research team published a population-based study in The Lancet Psychiatry in 2021 showing an increase in depressive symptoms and decrease in mental well-being among 13- to 18-year-old adolescents within 1 year of the global spread of the COVID-19 pandemic. A decline in substance use, in particular cigarette smoking, e-cigarette use, and alcohol intoxication, was also observed. Expanding on these findings, this new study shows that the negative effect on adolescent mental health persisted up to 2 years into the pandemic.

“It is worrisome that we still see an increase in mental health problems among adolescents 2 years into the pandemic. And this is occurring despite social restrictions having been eased in Iceland,” said Thorhildur Halldorsdottir, assistant professor of psychology at Reykjavik University and senior author of the study.

The initial decrease in cigarette smoking and e-cigarette use observed shortly after the arrival of the pandemic was also maintained up to 2 years into the pandemic. The frequency of adolescent alcohol intoxication, however, appeared to be returning to prepandemic levels. “It is of course positive to see that the reduction in cigarette smoking and vaping has been maintained,” said Ingibjorg Eva Thorisdottir, chief data analyst at Planet Youth and lead author of the study. She continued, “We will need to monitor alcohol intoxication among adolescents in years to come, especially given the increase in mental health problems.”

The association of immigration status, residency, parental social support, and nightly sleep duration with adolescent mental health and substance use was also examined in this study. Parental social support and an average of 8 hours or more of sleep per night was associated with better mental health and less substance use among adolescents. The relationship between immigration status and residency with adolescent mental health was less clear. These findings suggest that stress exposure, like the COVID-19 pandemic, affects all adolescents to some extent rather than only vulnerable subgroups.

How Lung Cells Protect Themselves Against RNA Viral Infection

A University of California, Irvine (UCI)-led study uncovered how a protein, APOBEC3B, could protect cells against many different types of RNA viruses, such as respiratory syncytial virus (RSV), SARS-CoV-2, influenza virus, poliovirus, and measles, helping to prevent disease. The study was published in Nature Communications and was funded by support from the National Institutes of Health.

Titled “APOBEC3B drives PKR-mediated translation shutdown and protects stress granules in response to viral infection,” the study findings provide an understanding of how lung cells, in particular, protect themselves against RNA viral infection. This discovery is essential to developing future therapies to limit viral infection and improve the health of patients with chronic lung disease.

RSV, SARS-CoV-2, influenza virus, poliovirus, and measles—all single-stranded RNA viruses—are some examples of highly contagious diseases transmitted by respiratory aerosols that commonly infect lung cells.

“Patients with chronic lung diseases, such as asthma, cystic fibrosis, chronic obstructive pulmonary disease, and interstitial lung diseases, are more susceptible to respiratory lung infections. These viral infections can further contribute to disease progression,” said Remi Buisson, PhD, assistant professor in the UCI School of Medicine Department of Biological Chemistry. “An exciting part of our finding fills a critical knowledge gap by illuminating how APOBEC3B can promote innate immune responses in host cells without generating mutations in the virus genomes and promoting viral evolution.”

In this study, graduate students Lavanya Manjunath and Sunwoo Oh, both at UCI School of Medicine in Dr. Buisson’s laboratory, utilized different RNA virus models, including Sendai virus, poliovirus, and Sindbis virus as tools, to determine how APOBEC3B regulates innate immune signaling in response to viral infection. Moreover, they found that APOBEC3B is recruited to stress granules through its interaction with PABPC1 to prevent stress granule destabilization and protect mRNAs associated with stress granules from an RNA endonuclease RNase L that cleave RNAs in host cells.

“We propose that APOBEC3B, in addition to its canonical role to edit viral genomes, functions with PABPC1 as important innate immunity mediators, protecting cells at different steps of the innate immune response against viral infections,” said Dr. Buisson.

More research is needed to develop strategies to prevent RNA viral infection.

“Our next steps are to determine the detailed mechanism of how APOBEC3B recognizes viral genome to promote an innate immune response and prevent viral replication,” said Dr. Buisson. “The goal is to identify how RNA viruses developed resistance mechanisms to counteract APOBEC3B functions and escape host cell defense.”

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