Abstract
We previously developed a temperature-sensitive, and NS1 gene deleted live attenuated influenza vaccine (DelNS1-LAIV) and demonstrated its potent protective efficacy in intranasally vaccinated mice. Here we investigated whether intradermal (i.d.) vaccination induces protective immunity. Our results showed that DelNS1-LAIV intradermal vaccination conferred effective and long-lasting protection against lethal virus challenge in mice. A single intradermal injection of DelNS1-LAIV conferred 100% survival with no weight loss in mice after A(H1N1)09 influenza virus (H1N1/415742Md) challenge. DelNS1-LAIV injection resulted in a significant reduction of lung viral load and reduced airway epithelial cell death and lung inflammatory cytokine responses at day 2 and 4 post challenge. Full protections of mice lasted for 6 months after immunization. In vitro infection of DelNS1-LAIV in monocyte-derived dendritic cells (MoDCs) demonstrated activation of antigen-presenting cells at 33 °C, together with the results of abortive replication of DelNS1-LAIV in skin tissue and strong upregulation of inflammatory cytokines/chemokines expression, our results suggested the strong immunogenicity of this vaccine. Further, we demonstrate that the underlying protection mechanism induced by intradermal DelNS1-LAIV is mainly attributed to antibody responses. Together, this study opens up an alternative route for the administration of LAIV, which may benefit individuals not suitable for intranasal LAIV immunization.
Highlights
The World Health Organization estimated that seasonal influenza causes about one billion infections globally each year, with 0.3–0.7 million deaths[1]
Against homologous H1N1/415742Md challenge To test whether live attenuated influenza vaccines (LAIV) is effective via intradermal route, 106 plaque forming units (PFU) of DelNS1-LAIV was i.d. injected to multiple groups of mice
Comparing i.d. vaccinated mice with i.n. vaccinated mice, there was no difference in body weight loss or survival rate (Fig. 1a), which suggested LAIV i.d. vaccination offered the same protective efficacy as i.n. vaccination
Summary
The World Health Organization estimated that seasonal influenza causes about one billion infections globally each year, with 0.3–0.7 million deaths[1]. LAIV is not recommended for children under 2 years old, people above 49 years old, pregnant women, and people with asthma or chronic obstructive lung diseases or immunocompromised conditions because these temperature-sensitive vaccine viruses with intact viral NS1 gene may replicate to higher titer in the respiratory tract to cause severe side effects[2]. Another potential risk is that vaccine virus may reassort with wild-type influenza viruses if simultaneous natural infection and immunization occur, the progeny virus is unlikely to be transmissible[6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
