At Boston Children's Hospital, immunologist Ivan Zanoni and his team have discovered that adding a natural immune booster to the COVID-19 mRNA vaccine extended protection from six months to two years in mice—a finding that could fundamentally change how often people need vaccination boosters.
The challenge facing vaccine science is both viral and biological. After six months, antibody levels from the original COVID-19 vaccine begin to drop, requiring people to return for boosters just to maintain protection. Meanwhile, the virus itself mutates rapidly, meaning the antibodies built from the original vaccine often fail to recognize newer variants circulating in the population. This has created a treadmill of boosters, each slightly less effective against the ever-evolving virus. Zanoni's research suggests a way to step off that treadmill entirely.
The key to their breakthrough is something called a "mannadjuvant"—an immune system enhancer created by combining mannan, a branched sugar molecule found on the outer cell wall of yeast called Candida, with alum, a vaccine adjuvant that has been safely used for decades. When the team paired this adjuvant with the original COVID-19 mRNA vaccine, the results were striking. Mice that received the combined vaccine maintained antibodies to the virus's spike protein for up to two years, compared to the six-month protection window of the vaccine alone.
The research, published in Nature Immunology, went further. When exposed to mutated spike proteins from omicron variants, mice vaccinated with the mannadjuvant showed stronger immune responses than those given the vaccine without the booster. "Our strategy takes advantage of the immune system's innate ability to generally ramp up in response to a variety of components found in and on pathogens," Zanoni explains. "Even though the mRNA technology is the biggest breakthrough for vaccine technology in the last couple decades, we thought that there is still room for us to improve this platform."
The science behind the mannadjuvant works by leveraging something our immune systems have evolved to recognize over millions of years: components from fungi and other pathogens that trigger a broader, more durable immune response. By including mannan—essentially a recognizable warning signal from nature—alongside the mRNA instructions, the vaccine itself becomes a more potent teacher for immune cells. Before testing in mice, Zanoni's team carefully verified that the vaccine remained stable when combined with the adjuvant, ensuring that this enhancement didn't compromise the delivery system that makes mRNA vaccines so effective.
This isn't the team's first success with the mannadjuvant approach. In earlier research, they used the same adjuvant to strengthen a protein-based influenza vaccine, suggesting the strategy could eventually work across different vaccine platforms. The implications are significant: if human trials confirm these findings, the combination could reduce the burden of repeated boosters while simultaneously improving protection against new variants—addressing both the practical inconvenience and the evolving threat simultaneously.
Zanoni's team has already filed patents on the mannadjuvant and launched a spinoff biotech company to advance the technology toward human trials. In the meantime, researchers plan to continue unraveling exactly how the adjuvant stimulates the immune system at a molecular level, particularly since the immune response to fungal components remains incompletely understood. The mannadjuvant represents a reminder that even breakthrough technologies like mRNA vaccines can be refined further—and that nature itself may hold the clues to making them better.