Researchers in Switzerland have developed a two-step Flu Vaccine approach that could offer stronger and longer-lasting protection against influenza. The strategy, which combines an intramuscular viral vector vaccine. A nasal spray of a live-attenuated flu virus has shown promising results in pigs. The findings, published in PLOS Pathogens, suggest the approach could improve flu prevention in humans, though further studies are needed.
Addressing Limitations of Traditional Flu Vaccine
Current flu vaccines, which are typically injected into the muscle, help the immune system recognize and fight influenza. However, they have limitations in preventing infection where it first takes hold—in the upper respiratory tract. This gap in protection can allow the virus to evolve and spread more quickly.
An alternative is live-attenuated influenza vaccines, which use weakened flu viruses administered through the nose. These vaccines trigger a broad immune response, including in the respiratory tract, where the virus enters the body. However, in early tests, the live-attenuated vaccine candidate, called NS1(1-126)-ΔPAX, while effective in pigs, was shed from their respiratory tract for an extended period. In humans, this could pose a risk for people with weakened immune systems if the virus were inadvertently transmitted.
A Two-Step Approach to Boost Immunity and Reduce Risks
To address these concerns, lead researcher Robin Avanthay and colleagues at the Institute of Virology and Immunology in Mittelhäusern, Switzerland, developed a two-step vaccination strategy. First, animals were given a priming dose using a viral vector. The vector is based on vesicular stomatitis virus (VSV), a commonly used vaccine delivery system. Unlike traditional VSV-based vaccines, this version was engineered to perform only a single round of infection, enhancing safety.
Four weeks later, the animals received the live-attenuated nasal vaccine. It is designed to trigger a strong immune response in the respiratory tract. The combination approach significantly improved immune defenses while reducing concerns about prolonged viral shedding.
Strong Protection Observed in Animal Trials
When tested in pigs, the two-step strategy generated a strong immune response throughout the body and in the upper respiratory tract, where flu infections begin. After exposure to a virulent flu strain, the vaccinated pigs showed no signs of infection, suggesting that the vaccine effectively blocked the virus from replicating and spreading.
Notably, the priming injection helped reduce the amount of the nasal vaccine shed by the animals, lowering the risk of transmission. The study also found that the two-step process boosted flu-specific antibodies and increased T-helper memory cells, which could extend the duration of immunity and improve protection against flu variants.
Potential for a Next-Generation Flu Vaccine
While the results are promising, further studies are needed before the two-step flu vaccination approach can be tested in humans. The strategy could offer better protection during seasonal flu outbreaks and reduce virus transmission.
“A novel prime/boost vaccination strategy against influenza was evaluated in the porcine animal model,” said co-author Dr. Gert Zimmer. “We combined the primary intramuscular immunization with a propagation-defective replicon vaccine with the secondary intranasal immunization using a genetically modified live-attenuated influenza vaccine. This resulted in reduced shedding, increased production of antibodies and memory cells, and full protection against the virus.”
As researchers continue to refine the approach, the findings highlight the potential for a next-generation flu vaccine that could provide broader and longer-lasting immunity.
Reference: Robin Avanthay, Obdulio Garcia-Nicolas, Nicolas Ruggli, Llorenç Grau-Roma, Ester Párraga-Ros, Artur Summerfield, Gert Zimmer. Evaluation of a novel intramuscular prime/intranasal boost vaccination strategy against influenza in the pig model. PLOS Pathogens, 2024.
