Enhancing Immunity Against Influenza B Using Interferons

Medical News: Influenza B infections have long posed a health challenge, especially during late flu seasons when they tend to peak. Despite widespread vaccination efforts, the effectiveness of influenza B vaccines has been limited, often sparking the need for alternative strategies to boost immunity. A recent study conducted by researchers from the U.S. Centers for Disease Control and Prevention (CDC), University of Georgia-USA, and Cleveland Clinic-USA explored how interferons, naturally occurring immune proteins, might enhance the body's defenses when administered alongside influenza B vaccinations or infections. Using ferrets as a model, the team investigated the impact of interferon treatments on immunity levels in the hopes of finding more effective ways to combat influenza B.


Enhancing Immunity Against Influenza B Using Interferons

Why Influenza B Remains a Challenge
Influenza B infections account for approximately a quarter of all flu cases. Unlike influenza A, which is divided into subtypes, influenza B viruses are classified into two main lineages: Yamagata and Victoria. Although less studied, these viruses are known to cause significant health issues, especially in children. Recent data shows that the average vaccine effectiveness for influenza B is around 54%, yet in certain seasons, such as 2014/2015, effectiveness rose to 57%. Even so, immune response rates remain inconsistent, with less than 20% of older children achieving a strong antibody response after vaccination.
 
This Medical News report examines a promising approach explored by the researchers, who sought to improve these responses by administering interferons - either type I or type III - following influenza B infection or vaccination.
 
Study Design: Using Interferons as Immunity Boosters
The research team designed their study using ferrets, a standard model in influenza research due to their similar respiratory responses to humans. The ferrets were either infected with influenza B or vaccinated and then given either a type I or type III interferon treatment to evaluate how interferons impacted their immune responses.
 
To ensure effective results, researchers carefully PEGylated the interferon proteins - a process that stabilizes them in the body - to see if they could help the immune system respond more vigorously to influenza B. The treatments were administered intranasally, which would deliver interferons directly to the respiratory tract where the flu virus takes hold.
 
Key Findings: How Interferons Affect Immune Responses
The study revealed several key insights into how interferons can act as an immune booster following influenza B infection or vaccination:
 
-Boosted Inflammatory and Immune Responses: Ferrets treated with interferons following infection showed early and robust inflammatory responses in the upper respiratory tract. This early response included increased production of thymic stromal lymphopoietin (TSLP), a signaling molecule known to stimulate adaptive immunity by he lping immune cells respond to infection.
 
-Enhanced Antibody Levels and Sustained Immunity: One of the standout findings was the significant increase in antibody levels in ferrets treated with interferons. These levels rose quickly after treatment and remained elevated over several months. This heightened antibody response suggested that interferons might help the body create a more durable immune defense against future influenza B challenges.
 
-Improved Resilience in Rechallenged Ferrets: To test long-term immunity, researchers rechallenged the ferrets three months after the initial infection or vaccination. Ferrets that had received interferon treatments displayed fewer symptoms and retained higher antibody levels than untreated animals, indicating a strengthened immune "memory" against the virus.
 
-Effect on Clinical Symptoms: Interferon-treated ferrets showed fewer clinical signs of influenza, such as lethargy, sneezing, and weight loss. These results were particularly notable in ferrets treated with type I interferon, which effectively reduced fever and other symptoms. Although ferrets treated with type III interferon (IFNL3) experienced some weight loss, their overall resilience was still higher than that of the untreated group.
 
-Cytokine and Chemokine Responses: Ferrets treated with interferons exhibited elevated levels of various cytokines, including type I and type III interferons, following infection. These immune proteins play an essential role in the body's antiviral response, helping to create an environment where the virus struggles to spread. In particular, type III interferon was associated with higher TSLP levels, which correlate strongly with the production of protective antibodies.
 
Relevance for Vaccine Development
The positive effects of interferon treatments on both the innate and adaptive immune responses may offer valuable insights for developing more effective flu vaccines. While influenza A vaccines have seen substantial advances, the current findings highlight a potential path to improve influenza B vaccines. By incorporating interferons as an adjuvant - an agent that enhances the body’s immune response - vaccines might stimulate stronger, longer-lasting immunity.

Interestingly, the study also observed that interferon treatments did not interfere with the replication of live-attenuated influenza B vaccines, suggesting that they could be safely used alongside vaccination to boost immunity without compromising vaccine efficacy. The ability of interferons to sustain immune responses in both vaccinated and infected animals underscores their potential as a complementary tool in flu prevention strategies.
 
Conclusions
The study findings indicate that interferon treatments may provide a valuable immune-boosting strategy for influenza B infections and vaccinations. By enhancing both innate and adaptive immune responses, interferons helped reduce symptoms, elevate antibody levels, and promote longer-lasting immunity in ferrets. These findings suggest that interferon-based approaches might improve vaccine effectiveness and could pave the way for more robust protection during flu season.
 
In conclusion, using interferons as an adjuvant appears promising for strengthening immune defenses against influenza B. The research indicates that interferons not only accelerate the immune response but also sustain it over time, a critical factor in minimizing the impact of influenza B on public health. Given the limited effectiveness of current influenza B vaccines, this approach may represent a significant advancement in flu prevention efforts, especially as researchers seek new ways to protect vulnerable populations.
 
The study findings were published in the peer-reviewed journal npj Vaccines.
https://link.springer.com/article/10.1038/s41541-024-00973-2
 
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