Abstract
Mast cells play pivotal roles in the pathogenesis of influenza A virus (IAV) infections. Defective viral particles (DPs) often arise during IAV replication, which can interfere with the replication of infectious viruses and stimulate the antiviral response of host cells. Therefore, DPs are expected to have immune-protective functions in clinic. However, the potent immunogenicity and effectiveness of DPs arising in mast cells during IAV replication have not been reported. In the present study, we showed that DPs generated in the human mastocytoma cell line HMC-1 following H1N1 infection were safe to mice after vaccination. Compared with lung adenocarcinoma cells, A549, DPs generated in infected mast cells had much better immunostimulatory activity, enhancing both humoral and cellular immunity of hosts. Notably, they could significantly increase the expression of immune-associated cytokines, especially the IFN-γ. Due to the robust immunogenicity, thus DPs generated in infected mast cells could stimulate the robust protective immune reaction effectively to fight against lethal IAV re-challenge after vaccination, which result in the high survival, decreased lung injury as well as inhibition of viral replication and inflammatory response in lungs. This study is the first to illustrate and explore the safety, immunogenicity, and effectiveness of DPs arising in mast cells against influenza as favorable potential vaccination. The results provide insight into the advances of new prophylactic strategies to fight influenza by focusing on DPs generated in mast cells.
Highlights
Influenza A virus (IAV) is a segmented negative-stranded RNA virus that can infect animals and humans
HD viruses isolated from H1N1-infected HMC-1 cells and A549 cells had the same I/T ratios, which were much lower than found in LD virus
Defective viral particles (DPs) can be generated in various kinds of cells and have two crucial functions: interfering with full-length virus replication and inducing antiviral responses in various cells during influenza A virus (IAV) infection, which are considered as potent vaccine adjuvants and broad-spectrum antivirals [20, 25]
Summary
Influenza A virus (IAV) is a segmented negative-stranded RNA virus that can infect animals and humans. It consists of eight gene segments (PB2, PB1, PA, HA, NP, HA, M, and NS) that together encode 17 different viral proteins [1, 2]. H1N1 human influenza virus can cause major epidemics in humans, which raises the perceived public health significance of influenza to a new level. Vaccination effectiveness may be variable from one season to another and seasonal vaccines are not effective against pandemic viruses, and new variants arise through antigenic drifts or shifts [4]. Development of novel broad-spectrum prophylactic agents against IAV is becoming research hotspots in public health and medicine
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