Researchers have reported a new, two-step approach for flu vaccination that combines an intramuscular injection of a viral vectored flu vaccine with a nasal spray of a novel weakened live flu virus, showing that it is both safe and effective in pigs. This work was conducted by Robin Avanthay and colleagues from the Institute of Virology and Immunology in Mittelhäusern, Switzerland, and their findings are published in the open-access journal PLOS Pathogens.
Traditional seasonal flu vaccines typically involve injecting inactivated parts of the flu virus into muscle, allowing the immune system to learn to combat the virus. However, this method has limited effectiveness when it comes to preventing infection at the upper respiratory tract’s initial point of entry, and it may contribute to the emergence of new flu strains that can escape the immune response.
A promising alternative is the use of live-attenuated vaccines, which consist of a modified version of the flu virus that is weakened so it cannot cause illness. These vaccines can be given through the nose, targeting the upper respiratory tract directly, which triggers a comprehensive immune response against the flu. The researchers’ new candidate for a live-attenuated vaccine elicits a robust local immune reaction that protects pigs from the flu virus. Although this vaccine did not produce symptomatic effects in pigs, it was noted to be shed from their upper respiratory tract for an extended period. If such a vaccine were utilized in humans, there’s a risk that it could be passed on to individuals with weakened immune systems, potentially leading to health complications.
To mitigate the benefits and risks, Avanthay and the team created a two-step vaccination technique. Initially, before the nasal application of the live vaccine candidate known as NS1(1-126)-ΔPAX, they primed the animals with a vesicular stomatitis virus (VSV) that served as a delivery system. VSV is considered a promising vector in vaccine research. In this study, the VSV-vectored vaccine was engineered to be “propagation-defective,” meaning it could only infect once, enhancing safety.
When this approach was tested on pigs, it produced a strong immune reaction both throughout the body and particularly in the upper respiratory tract, the area where flu infections begin. After being exposed to a virulent flu virus, no infections were detected in the pigs that underwent the two-step vaccination. Thus, this innovative immunization approach shows potential for effectively blocking flu virus replication in the upper respiratory tract, which may help reduce the shedding and transmission of the flu during seasonal outbreaks.
Compared to pigs that were given only the NS1(1-126)-ΔPAX vaccine, those vaccinated using the two-step method exhibited significantly less shedding of the vaccine from their upper respiratory tract. Notably, the intranasally delivered live vaccine enhanced the systemic production of Flu-specific antibodies and increased the frequency of Flu-specific T helper memory cells, an outcome that was also observed when the live vaccine was directly administered without prior priming. This new two-step vaccination method may help extend the duration of protective immunity and improve defense against various flu virus strains.
The researchers conclude that this innovative two-step method shows promise as a next-generation strategy for more effectively combating flu, although further testing is necessary before this vaccine can be used in humans.
Co-author Dr. Gert Zimmer summarizes, “We evaluated a novel prime/boost vaccination strategy against influenza using a porcine model. Our approach combined a primary intramuscular immunization with a propagation-defective replicon vaccine, followed by a secondary intranasal immunization using a genetically modified live-attenuated influenza vaccine (LAIV). This regimen resulted in reduced shedding of LAIV, increased production of specific serum IgG, neutralizing antibodies, Th1 memory cells, and offered complete protection against homologous virus challenges in the animals.”
