New two-step vaccination strategy for influenza

Researchers at the Institute of Virology and Immunology, Switzerland, have developed a novel, two-step flu vaccination strategy that combines intramuscular injection of a viral vectored flu vaccine with nasal spray administration of a new attenuated live flu virus. This approach appears to be safe and effective in porcine models.

Live-attenuated vaccines are more effective than seasonal flu vaccines. The teams’ live-attenuated vaccine candidate induced a potent local immune response that protected pigs against flu virus, although it was shed from the upper respiratory tract for a prolonged time. Therefore, there is a chance that it could be transmitted to individuals with compromised immune systems, if used in humans.

Robin Avanthay and his colleagues developed a two-step immunisation strategy to balance the advantages and risks. The pigs were primed with a vesicular stomatitis virus (VSV) as a vaccine delivery mechanism, a promising vector approach. Then, the live-attenuated flu vaccine candidate, NS1(1-126)-ΔPAX, was nasally administered. Contrastingly to frequently used VSV-vectored vaccines, the vaccine used in this study was propagation-defective, engineered to perform only a single round of infection for safety.

A strong immune response was seen both body-wide and specifically in the upper respiratory tract where initial flu infection occurs. Also, no infection was identified in the two-step-vaccinated pigs, following exposure to virulent flu virus. Compared to pigs that only received NS1(1-126)-ΔPAX, the two-step-vaccinated pigs demonstrated much less shedding of the vaccine candidate from their upper respiratory tract. Notably, the intranasally administered live vaccine enhanced the systemic flu-specific antibody response and higher frequencies of flu-specific T helper memory cells were seen.

Although further testing is required before this approach can be used in humans, the scientists believe that this new two-step vaccination strategy could enable the duration of protective immunity, and protection against flu virus variants.

This study was published in PLOS Pathogens.