Long regarded as disease-specific, some widely used vaccines may confer broader health benefits that extend beyond protection against intended pathogens.

Evidence suggests that certain live attenuated vaccines may reduce all-cause mortality and protect against unrelated diseases, raising questions about how vaccine effects are evaluated and how immunization policies are designed and implemented.

The Bacillus Calmette-Guérin (BCG) vaccine, first administered in 1921, is the most extensively studied example. In addition to its role in preventing tuberculosis, BCG has been associated with protective effects against other respiratory diseases. In settings with high infant mortality, BCG vaccination has been linked to a 30%-53% reduction in all-cause mortality among children younger than 5 years.

Similar observations have been reported for the measles vaccine, which has been associated with a 26%-49% reduction in mortality in this age group beyond protection against measles alone. Comparable effects have also been described for the oral poliovirus vaccine, which has been widely used in low- and middle-income settings.

Live Vaccines and Innate Immunity

These three vaccines share a key characteristic: They are all live-attenuated vaccines. For reasons thought to be related to innate immunity, the first line of immune defense preceding antibody-mediated adaptive immunity, these vaccines may induce protective effects against diseases other than their specific targets. This phenomenon has been described as a nonspecific effect of vaccination.

Among the most influential researchers in this field are Christine Stabell Benn, MD, PhD, DMSc, professor of global health at the University of Southern Denmark, who has worked at the Bandim Health Project (BHP), and Peter Aaby, PhD, founder of the BHP at the BHP Open Patient Data Explorative Network, Department of Clinical Research, and Danish Institute for Advanced Study, University of Southern Denmark, Odense, Denmark.

Together, they are coauthors of approximately 35% of the studies published on nonspecific vaccine effects. Benn recently argued in the journal Vaccine that vaccination policies should be reconsidered considering these findings and that nonspecific effects should be considered when vaccines are evaluated.

Scientific Dispute

These conclusions have been strongly criticized. A recent analysis published in Vaccine by Henrik Støvring, DMSc, professor from the Department of Biomedicine, Aarhus University, and Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark, and colleagues questioned the quality of the statistical analyses used and raised the possibility of false-positive findings published by researchers in the BHP.

“We uncovered elements suggesting that the researchers systematically selected and highlighted results supporting their theory while downplaying those that did not. When considering the entire body of work, there are almost no positive results.”

This critique represents a significant challenge for the BHP, which published a response addressing the concerns raised by its critics. Støvring and colleagues emphasized that they do not dispute the existence of nonspecific effects of certain vaccines, which have also been reported by researchers other than the BHP. However, they argued that these findings should be interpreted cautiously and regarded as exploratory data awaiting confirmation.

Beyond Infectious Diseases

Another study reported nonspecific effects associated with live-attenuated vaccines. Research involving newborns vaccinated with BCG has shown substantial reductions in infant mortality, with one death prevented in every 21 vaccinated children.

Some vaccines may have clinical relevance, in addition to infectious diseases. BCG is now routinely used in the treatment of bladder cancer, known as BCG therapy, and its potential effects on melanoma and hepatocellular carcinoma have been investigated.

Additional studies have suggested a preventive effect against Alzheimer’s disease and other age-related dementias in patients receiving BCG for bladder cancer.

Research has also pointed to the possible benefits in type 1 diabetes, including its effects on glycemic control in individuals with this condition.

Finally, research on experimental live attenuated intranasal pertussis vaccines has suggested potential protective effects against asthma and chronic obstructive pulmonary disease based on preclinical evidence showing reduced allergic airway inflammation and improved lung function in animal models.

This story was translated from MediQuality, part of the Medscape Professional Network.