Abstract
The non-specific effects (NSEs) of vaccines have been discussed for their potential long-term beneficial effects beyond direct protection against a specific pathogen. Cold-adapted, live attenuated influenza vaccine (CAIV) induces local innate immune responses that provide a broad range of antiviral immunity. Herein, we examined whether X-31ca, a donor virus for CAIVs, provides non-specific cross-protection against respiratory syncytial virus (RSV). The degree of RSV replication was significantly reduced when X-31ca was administered before RSV infection without any RSV-specific antibody responses. The vaccination induced an immediate release of cytokines and infiltration of leukocytes into the respiratory tract, moderating the immune perturbation caused by RSV infection. The potency of protection against RSV challenge was significantly reduced in TLR3-/- TLR7-/- mice, confirming that the TLR3/7 signaling pathways are necessary for the observed immediate and short-term protection. The results suggest that CAIVs provide short-term, non-specific protection against genetically unrelated respiratory pathogens. The additional benefits of CAIVs in mitigating acute respiratory infections for which vaccines are not yet available need to be assessed in future studies.
Highlights
Respiratory viral infections, caused by influenza virus, respiratory syncytial virus (RSV), human parainfluenza viruses (HPIVs), and coronaviruses, remain a global public health concern (WHO, 2013)
To confirm the safety of CAIV, mice injected with 106 plaqueforming units (PFU) of X-31ca were monitored for any weight change daily for 2 weeks
RSV titer was measured only in HEp-2 cells, as the lung viral titer from parallel immunization of X-31ca, without RSV challenge, was below the detection level within 4 days of immunization. These results demonstrate that X-31ca vaccination could confer early, short-term protection against RSV challenge in mice
Summary
Respiratory viral infections, caused by influenza virus, respiratory syncytial virus (RSV), human parainfluenza viruses (HPIVs), and coronaviruses, remain a global public health concern (WHO, 2013). Except for influenza virus, there are no authorized vaccines available for the prevention of emerging/re-emerging respiratory viral infections (Hall, 2001). Vaccination is based on the adaptive immune responses that provide protection against a specific pathogen. The possibility remains, that NSE may operate in an immediate manner for short-term protection, especially considering the potent antiviral responses of the innate immune system (Takeuchi and Akira, 2009). Such an effect is expected to be quite significant, especially with live attenuated vaccines that mimic natural infections (Seo et al, 2007). Live influenza vaccination was found to be associated with an immediate and indirect protection from respiratory illness among children (Piedra et al, 2007)
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