Simple Solution Improves Flu Vaccine

For decades, immunologists have been on a frenetic quest to find the holy-grail for influenza vaccines—a cross-protective mixture that would allow the immune system to react to a variety of flu strains after a single inoculation. Now, researchers at the University of Melbourne may have found a fairly simple workaround that boosts the effectiveness and cross-protective capabilities of the influenza A vaccine through the addition a simple detergent-like adjuvant compound.

“Influenza infections cause 250,000-500,000 deaths every year. Our best protection comes from the seasonal flu vaccine, which induces antibodies that neutralize the virus,” explained lead author Brendon Chua, Ph.D., research fellow at the University of Melbourne. “The holy grail would be to develop a vaccine that cross-protects against different strains, which would be beneficial for the whole community, even if the prediction of circulating strains is wrong.”

The findings from this study were published recently in mBio through an article entitled “Inactivated Influenza Vaccine That Provides Rapid, Innate-Immune-System-Mediated Protection and Subsequent Long-Term Adaptive Immunity.”

The investigators believed that the addition of the proper adjuvant along with the flu vaccine would stimulate other types of antibody-independent immune responses, resulting in a much improved and cross-protective vaccine.

“We had an adjuvant that worked well to stimulate both innate and adaptive immunity,” noted Dr. Chua. “Harnessing both types of immunity would provide protection in that period during an outbreak when no [new] vaccine is available.”

Innate immunity is the body’s first line of defense against that quickly attacks foreign antigens in a nonspecific manner. Conversely, the adaptive immune response is the body’s long-term response, which typically generates immune memory specific to the antigen it is trying to attack.

The adjuvant in this study called R₄Pam₂Cys, is a synthetic lipopeptide—a string of fat molecules connected by a small protein chain that mimics a natural component found on the outer membrane of a pathogenic microorganism. Human immune cells recognize this component as a danger signal.

“This danger signal is the key to the front door of innate immunity,” stated senior author David Jackson, Ph.D. professor and vaccine expert at the University of Melbourne. “It initiates the nonspecific innate response that says, ‘Get the SWAT squad out here!’ “

The Melbourne team added the adjuvant to an inactivated influenza A vaccine, inoculated mice, and then exposed them three days later to both the virus contained in the vaccine, as well as an additional strain. The mice given the adjuvanted vaccine were better protected compared to mice that received the vaccine without the adjuvant. Moreover, mice given the adjuvanted vaccine also survived what is normally a lethal dose of the flu virus.

Furthermore, mice that were given a low dose of the adjuvanted vaccine as a nasal application produced 600 times more neutralizing antibodies compared to a similar low dose of vaccine alone. Notably, the adjuvant-vaccine combo also activated more T cells that handle clearing flu-infected cells in the lungs.

“The culmination of all these responses is that it reduces the ability of the virus to infect cells, reproduce, and spread,” Dr. Chua said.

To test their tincture even further, Dr. Chua and his colleagues gave mice the low-dose adjuvant-vaccine combo and challenged them with flu virus strains 35 days later. The mice were completely protected against the strain contained in the vaccine, and against an unmatched strain not contained in the vaccine. In contrast, mice receiving the low-dose vaccine alone were not significantly protected from either flu strain.

“The biggest advantage is that this approach doesn’t rely on getting a match between the strains used in the vaccine and circulating virus—you can still get some protective effect at the population level,” concluded Dr. Chua.