US Pharm. 2024;49(4):26-29.

Flu Vaccines Likely to Move From Quadrivalent to Trivalent

Currently, all influenza vaccines in the United States are quadrivalent, meaning that they protect against four different flu viruses. According to a University of Michigan (U-M) researcher, however, U.S. influenza vaccines are likely to move from quadrivalent to trivalent due to a change in circulating influenza viruses.

In an article published in the New England Journal of Medicine, researchers detailed the spread of influenza B/Yamagata virus, which has not been in circulation since early 2020; the regulatory discussions and recommendations on updating vaccines; and the manufacturing considerations for new vaccine formulations for the U.S. and abroad.

“The removal of B/Yamagata virus is logical as we do not want to include a virus in vaccine formulation that is no longer in circulation,” said Arnold Monto, professor emeritus of epidemiology and global public health at the U-M School of Public Health.

“It also gives us the space to replace B/Yamagata virus with a component that will give improved protection against the circulating influenza viruses. That will take additional studies to accomplish.”

Dr. Monto, who has dedicated his career to researching the occurrence, prevention, and control of respiratory infections, also serves as a member of the FDA’s Vaccines and Related Biological Products Advisory Committee.

New Approach to Battling Bacterial Infections

Researchers have identified a new approach to controlling bacterial infections, finding a way to turn on a vital bacterial defense mechanism to fight and manage bacterial infections. The defense system, called cyclic oligonucleotide-based antiphage signaling system (CBASS), is a natural mechanism used by certain bacteria to protect themselves from viral attacks. Bacteria self-destruct as a means to prevent the spread of virus to other bacterial cells in the population.

The findings by researchers at the Icahn School of Medicine at Mount Sinai in New York City were described in Nature Structural & Molecular Biology.

“We wanted to see how the bacterial self-killing CBASS system is activated and whether it can be leveraged to limit bacterial infections,” said cosenior author Aneel Aggarwal, PhD, professor of pharmacological xciences at Icahn Mount Sinai. “This is a fresh approach to tackling bacterial infections, a significant concern in hospitals and other settings. It’s essential to find new tools for fighting antibiotic resistance. In the war against superbugs, we need to constantly innovate and expand our toolkit to stay ahead of evolving drug resistance.”

According to a 2019 report by the CDC, more than 2.8 million antimicrobial-resistant infections occur in the U.S. each year, with over 35,000 people dying as a result.

As part of the experiments, the researchers studied how Cap5, or CBASS-associated protein 5, is activated for DNA degradation and how it could be used to control bacterial infections through a combination of structural analysis and various biophysical, biochemical, and cellular assays. Cap5 is a key protein that becomes activated by cyclic nucleotides (small signaling molecules) to destroy the bacterial cell’s own DNA.

“In our study, we started by identifying which of the many cyclic nucleotides could activate the effector Cap5 of the CBASS system,” said cosenior author Olga Rechkoblit, PhD, assistant professor of pharmacological sciences at Icahn Mount Sinai. “Once we figured that out, we looked closely at the structure of Cap5 when it’s bound to these small signaling molecules. Then, with expert help from Daniela Sciaky, PhD, a researcher at Icahn Mount Sinai, we showed that by adding these special molecules to the bacteria’s environment, these molecules could potentially be used to eliminate the bacteria.”

Mouth Ulcer Virus Doubles Dementia Risk

People who have had the herpes virus at some point in their lives are twice as likely to develop dementia compared with those who have never been infected. A new study from Uppsala University in Sweden confirmed previous research on whether herpes can be a possible risk factor for dementia.

The researchers studied 1,000 70-year-olds from Uppsala over 15 years. The study, published in the Journal of Alzheimer’s Disease, found that people who had been infected with the herpes simplex virus at some point in their lives were twice as likely to develop dementia compared with those who had never been infected.

The herpes simplex virus is very common, and up to 80% of Swedish adults may be infected. The infection is lifelong, but the symptoms can come and go over different periods of life, and many people never get any symptoms linked to their infection.

“What’s special about this particular study is that the participants are roughly the same age, which makes the results even more reliable since age differences, which are otherwise linked to the development of dementia, cannot confuse the results,” explained Erika Vestin, a medical student at Uppsala University.

Fifty-five million people worldwide are affected by dementia. Advanced age and carrying the apolipoprotein 4 risk gene are already known risk factors. Research has previously been conducted to investigate whether the herpes simplex virus could also be a possible risk factor for dementia, which this study confirmed.

“It is exciting that the results confirm previous studies. More and more evidence is emerging from studies that, like our findings, point to the herpes simplex virus as a risk factor for dementia,” said Ms. Vestin.

Important conclusions from the study include the need to further investigate whether already known drugs against the herpes simplex virus can reduce the risk of dementia and the possibility of developing new vaccines. “The results may drive dementia research further towards treating the illness at an early stage using common antiherpes virus drugs or preventing the disease before it occurs,” added Ms. Vestin.

Lockdowns’ Impact on Newborn Gut Microbes

Lockdowns imposed during the COVID-19 pandemic had an impact on the gut microbiome development of babies born during these periods, according to researchers in Ireland.

The study published in Allergy is the first to explore the gut health of newborns in the pandemic. It revealed significant differences in the microbiome development of babies born during lockdown periods when compared with prepandemic babies. Babies born during lockdown also had lower than expected rates of allergic conditions, such as food allergies.

The research was conducted by scientists at RCSI University of Medicine and Health Sciences, Children’s Health Ireland, and APC Microbiome Ireland (APC), a research center based at University College Cork, Ireland.

The findings highlighted gut health benefits for “pandemic babies” arising from the unique environment of lockdown, including lower rates of infection and consequent antibiotic use, and increased duration of breastfeeding. The newborns were found to have more of the beneficial microbes acquired after birth from their mothers. These maternal microbes could be playing a protective role against allergic diseases.

Jonathan Hourihane, head of the Department of Paediatrics at RCSI, consultant pediatrician at Children’s Health Ireland Temple Street, who is joint senior author of the study, commented on the research’s implications. “This study offers a new perspective on the impact of social isolation in early life on the gut microbiome. Notably, the lower allergy rates among newborns during the lockdown could highlight the impact of lifestyle and environmental factors, such as frequent antibiotic use, on the rise of allergic diseases.

“We hope to re-examine these children when they are 5 years old to see if there are longer term impacts of these interesting changes in early gut microbiome,” Dr. Hourihane said.

Liam OMahony, principal investigator at APC Microbiome Ireland and professor of immunology at University College Cork, is joint senior author. He added, “While we all start life sterile, communities of beneficial microbes that inhabit our gut develop over the first years of life. We took the opportunity to study microbiome development in infants raised during the early COVID-19 era when strict social distancing restrictions were in place, as the complexity of early life exposures was reduced, and this facilitated a more accurate identification of the key early life exposures. Prior to this study, it has been difficult to fully determine the relative contribution of these multiple environmental exposures and dietary factors on early life microbiome development.

“One fascinating outcome is that due to reduced human exposures and protection from infection, only 17% of infants required an antibiotic by one year of age, which correlated with higher levels of beneficial bacteria such as bifidobacteria. The study has provided a rich repository of data, which we will continue to analyze and investigate in the future,” Dr. OMahony added.

The researchers from RCSI, CHI, and APC Microbiome Ireland analyzed fecal samples from 351 babies born in the first 3 months of the pandemic, comparing these with prepandemic cohorts. The former were part of the Impact of CoronaVirus Pandemic on Allergic and Autoimmune Dysregulation in Infants Born During Lockdown project. Online questionnaires were used to collect information on diet, home environment, and health. Stool samples were collected at 6,12, and 24 months, and allergy testing was performed at 12 and 24 months.

People Inclined to Hide Contagious Illness

A large number of people conceal an infectious illness to avoid missing work, travel, or social events, research at the University of Michigan suggested.

The findings were reported in Psychological Science. Across a series of studies involving healthy and sick adults, 75% of the 4,110 participants said that they had either hidden an infectious illness from others at least once or might do so in the future. Many participants reported boarding planes, going on dates, and engaging in other social interactions while secretly sick. More than 61% of healthcare workers participating in the study also said that they had concealed an infectious illness.

Interestingly, the researchers found a difference between how people believe they would act when ill and how they actually behave, said Wilson N. Merrell, a doctoral candidate and lead author on the study.

“Healthy people forecasted that they would be unlikely to hide harmful illnesses—those that spread easily and have severe symptoms—but actively sick people reported high levels of concealment regardless of how harmful their illness was to others,” said Dr. Merrell.

In the first study, Dr. Merrell and his colleagues, psychology professor Joshua M. Ackerman and PhD student Soyeon Choi, recruited 399 university healthcare employees and 505 students. The participants reported the number of days they felt symptoms of an infectious illness, starting in March 2020 when the COVID-19 pandemic began. They then rated how often they actively covered up symptoms from others, came to campus or work without telling others they were feeling ill, or falsified mandatory symptom screeners that the university had required for anyone using campus facilities.

More than 70% of the participants reported covering up their symptoms. Many said that they hid their illness because it would conflict with social plans, while a small percentage of participants cited pressure from institutional policies (e.g., lack of paid time off). Only five participants reported hiding a COVID-19 infection.

In a second study, the researchers recruited 946 participants online and randomly assigned them to one of nine conditions in which they imagined being either moderately or severely sick while in a social situation. In each condition, the risk of spreading the illness was designated as low, medium, or high. (To control for the special stigma associated with COVID-19 at the time, the researchers asked participants not to imagine being sick with that disease.) Participants were most likely to envision themselves hiding their sickness when symptom severity was low, and they were least likely to conceal when symptoms were severe and highly communicable.

In another study, Dr. Merrell and colleagues used an online research tool to recruit 900 people, including some who were actively sick, and asked them to rate the transmissibility of their real or imagined illness. The participants were also asked to rate their likelihood of covering up an illness in a hypothetical meeting with another person.

Results showed that compared with healthy participants who only imagined being sick, those who were actively ill were more likely to conceal their illness regardless of its transmissibility.

“This suggests that sick people and healthy people evaluate the consequences of concealment in different ways,” Dr. Merrell said, “with sick people being relatively insensitive to how spreadable and severe their illness may be for others.”

The COVID-19 crisis may have shaped the way the participants thought about concealing an illness, he said, adding that future research could explore how ecological factors (e.g., pandemics) and medical advances such as vaccines influence people’s disease-related behavior. The research team is also expanding this line of investigation to other countries to uncover potential cultural differences in concealment behaviors, he added.

How Viruses Cause Cancer, Potential Treatment

Cleveland Clinic researchers discovered a key mechanism used by Kaposi’s sarcoma–associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), to induce cancer. The research points to effective new treatment options for KSHV-associated cancers, including Kaposi’s sarcoma, primary effusion lymphoma, and HHV8-associated multicentric Castleman disease.

“Our findings have significant implications: viruses cause between 10% to 20% of cancers worldwide, a number that is constantly increasing as new discoveries are made. Treating virus-induced cancers with standard cancer therapies can help shrink tumors that are already there, but it doesn’t fix the underlying problem of the virus,” said Jun Zhao, PhD, of Cleveland Clinic Florida Research & Innovation Center. “Understanding how pathogens transform a healthy cell into a cancer cell uncovers exploitable vulnerabilities and allows us to make and repurpose existing drugs that can effectively treat virus-associated malignancies.”

The study in Nature Communications, led by Dr. Zhao, revealed that KSHV manipulates two human enzymes called CDK6 and CAD to reshape the way human cells produce new nucleotides, the building blocks of DNA and RNA, and process glucose. The changes to how infected cells grow and how KSHV persists put cells at a much higher risk of forming tumors and play a crucial role in causing cancer.

The team showed the virus activates a specific pathway driving cell metabolism and proliferation. Inhibiting this process with existing FDA-approved breast cancer drugs reduced KSHV replication, blocked lymphoma progression, and shrank existing tumors in preclinical models.

Like other herpesviruses, KSHV often has no symptoms initially and remains in the body after primary infection. The virus stays dormant, suppressed by the immune system. However, KSHV can reactivate when immunity is weakened—as in older people, those with HIV/AIDS, and transplant recipients. In these high-risk groups, the now-active virus can trigger aggressive cancers.

KSHV-induced cancers are fast-acting, aggressive and difficult to treat. An estimated 10% of people in North America and Northern Europe have KSHV, but this ranges throughout the globe. More than 50% of individuals in parts of Northern Africa are estimated to have the virus. Experts estimate that these rates are higher, as KSHV often goes undiagnosed because of lack of symptoms. These findings have implications that reach past KSHV; for example, the scientists said that researchers can apply knowledge about KSHV to other cancer-associated viruses that might use the same process to cause cancer.

To understand the cells’ metabolic processes to uncover the virus’ vulnerabilities, Dr. Zhao collaborated with Michaela Gack, PhD, scientific director of the Florida Research & Innovation Center.

Rapidly replicating cancer cells reprogram metabolism to fuel growth. Meanwhile, most viruses cannot produce energy or necessary molecules on their own, so they rely on human cells to do the work for them. The team found that the virus takes over the host protein CDK6 and CAD, causing the infected cells to produce extra metabolites, which allows faster replication of the virus and an uncontrolled proliferation of the cells.

The research team treated preclinical models with a CDK6-blocking drug, palbociclib, an FDA-approved breast cancer medication, as well as a compound targeting CAD. They saw significant decreases in tumor size and increases in cancer survival rates: Most tumors virtually disappeared after about a month of treatment, and remaining tumors shrank around 80%. Survival increased to 100% for selected lymphoma cell lines.

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