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Immunologic Agent Shows Promise for Optimizing Vaccines' Efficacy

Mahyar Nouri-Shirazi, DVM, PhD, is associate professor of biomedical science in FAU's Charles E. Schmidt College of Medicine. 

Mahyar Nouri-Shirazi, DVM, PhD, associate professor in the Charles E. Schmidt College of Medicine at Florida Atlantic University, has identified an immunologic agent that shows promise for optimizing vaccines’ efficacy, particularly in smokers, and in children or adults exposed to environmental tobacco. Shirazi aims to determine how this agent in contrast to other agents already in vaccines or late clinical development can restore vaccine responsiveness in nicotine-exposed hosts. He has received a two-year, $148,958 R03 grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health for his project titled “Overcoming the Degrading Effects of Nicotine on Vaccine Using TLR Agonists.”

“Nicotine has adverse effects on the body’s immune system and its ability to recognize and react to abnormal cells in the body, increasing susceptibility to cancer and infectious diseases,” says Shirazi. “Nicotine also has degrading effects on the outcome of vaccinations and there is compelling evidence that smokers are less responsive to vaccines and have a higher incidence and severity of infectious diseases.”

Vaccines are one of the most successful means of preventing communicable disease spread to humans, providing an important tool for protecting high risk groups such as the elderly, newborns or those who are immunocompromised. However, vaccines for these susceptible populations don’t always provide sufficient effectiveness, particularly in tobacco smokers where nicotine can degrade vaccine effectiveness.

Shirazi’s team is making progress in understanding the mechanisms that underlie impairments in vaccine-induced immunity and nicotine-induced defects in the activity of dendritic cells, which are key cells for the immune system. They have identified a defect in the link between dendritic cells and natural killer cells, also known as NK cells, which play a major role in the host-rejection of both tumors and virally infected cells. These researchers have discovered a candidate agent with potential to repair nicotine-impaired immune cells and improve vaccine immunogenicity by restoring the interactions between dendritic and NK cells.

Vaccinations serve as a “firewall” in the spread of disease. When a significant portion of a population is vaccinated, the spread of disease is limited and vulnerable or unvaccinated individuals are protected from contracting the disease. This principle of “herd immunity” is an effective way to extend the benefit of vaccinations beyond a directly targeted population. The reduced efficacy and protection seen in smokers as compared to non-smokers following vaccination is therefore a significant hurdle in maintaining public health, particularly during an epidemic season, in a pandemic outbreak or in the event of biological warfare.

Despite substantial progress in tobacco control and cessation, according to the World Health Organization (WHO), there are more than 1 billion smokers worldwide and almost half of the world’s children breathe air polluted by tobacco smoke. In the U.S., approximately 20 percent of adults and 30 percent of military personnel are smokers, 22 million children are exposed to secondhand smoke and 43 percent of non-smokers have detectable levels of cotinine, a substance found in tobacco.

“This large population of smokers in the U.S. and globally impacts the herd immunity effect of vaccinations, which is critical for protecting individuals who cannot be vaccinated due to medical conditions such as immune disorders, organ transplants, and pregnancy, and for those in whom vaccination is not effective, such as newborns, the elderly and smokers themselves,” says Shirazi.

Herd immunity had a major impact in the eradication of smallpox, protects against influenza and pneumonia and has reduced the transmission of pertussis or whooping cough, a highly contagious respiratory disease.

“Dr. Shirazi’s research tests an innovative approach for increasing the effectiveness of future vaccines that could also work well in smokers and those exposed to environmental tobacco,” says John W. Newcomer, MD, vice dean for research and graduate programs at FAU’s Charles E. Schmidt College of Medicine. “The ultimate goal of this project is to protect the public health.”

Source: Florida Atlantic University

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