A live attenuated vaccine prevents replication and transmission of H7N9 highly pathogenic influenza viruses in mammals

Abstract

H7N9 influenza viruses emerged in 2013 and have caused severe disease and deaths in humans in China. Some H7N9 viruses circulating in chickens have mutated to highly pathogenic viruses that have caused several disease outbreaks in chickens. Studies have shown that when the H7N9 highly pathogenic viruses replicate in ferrets or humans, they easily acquire certain mammalian-adapting mutations and become highly lethal in mice and highly transmissible in ferrets by respiratory droplet, creating the potential for human-to-human transmission. Therefore, the development of effective control measures is a top priority for H7N9 pandemic preparedness. In this study, we evaluated the protective efficacy of a cold-adapted, live attenuated H7N9 vaccine (H7N9/AAca) against two heterologous H7N9 highly pathogenic viruses in mice and guinea pigs. Our results showed that one dose of the H7N9/AAca vaccine prevented disease and death in mice challenged with two different H7N9 highly pathogenic viruses, but did not prevent replication of the challenge viruses; after two doses of H7N9/AAca, the mice were completely protected from challenge with A/chicken/Hunan/S1220/2017(H7N9) virus, and very low viral titers were detected in mice challenged with H7N9 virus CK/SD008-PB2/627 K. More importantly, we found that one dose of H7N9/AAca could efficiently prevent transmission of CK/SD008-PB2/627 K in guinea pigs. Our study suggests that H7N9/AAca has the potential to be an effective H7N9 vaccine and should be evaluated in humans.

H7N9 Influenza Virus in China

“…He et al 2018 (HA) Hemagglutinin, (NA) neuraminidase, (HPAIVs) highly pathogenic avian influenza viruses, (ELISA) enzyme-linked immunoabsorbent assay. sion differs in different studies (Belser et al 2013;Richard et al 2013;Watanabe et al 2013;Zhang et al 2013a;Zhu et al 2013;Xu et al 2014;Kong et al 2015;Imai et al 2017;Shi et al 2017;Yang et al 2018b). For example, the respiratory droplet transmissibility of a series of H7N9 viruses was shown to vary from low to high in studies by Zhang et al (2013a) and Kong et al (2019).…”

A Novel Reassortant Avian H7N6 Influenza Virus Is Transmissible in Guinea Pigs via Respiratory Droplets

“…Compared to the closely related HB93, HB95 displayed an advantage for transmission via respiratory droplets in the guinea pig model (Figure 6). Several research groups have evaluated the transmissibility of H7N9 viruses in guinea pig model and some H7N9 viruses strains indeed transmit via aerosol in guinea pigs (Kong et al, 2015; Yang et al, 2018). But the HB93 virus in our study only transmitted via direct contact but not via respiratory droplets in guinea pigs.…”

“…Such as low viral shedding in guinea pigs, the avian H7N9 A/chicken/Hunan/S1220/2017(H7N9) virus in Yang et al study which was airborne transmissible peaks more than 10 6 EID 50 /mL in guinea pigs, with virus titers more than 1000-fold higher than 10 3 EID 50 /mL of HB93 in our study; amino acid changes in H7N9 viruses which would make the influenza viruses transmissible in animal model, such as amino acids in PB2, lysine at position 627K and 701N which some human H7N9 isolates encode, are important for influenza transmission in ferret and guinea pig models (Watanabe et al, 2014), the H7N9 (HB93) virus in our study contains neither 627K nor 701N in the PB2 gene which might lead the limited transmissibility in the guinea pig model. The Ferrets have been widely used as animal models for H7N9 influenza virus transmission studies and some H7N9 viruses exhibit limited transmission via respiratory droplets (Richard et al, 2013), but airborne transmissible in the guinea pig model (Kong et al, 2015; Yang et al, 2018). The HB93 virus in this study only exhibited direct contact transmission but no airborne transmission in guinea pig model; the HB95 also contains neither 627K nor 701N in the PB2 gene, but exhibited airborne transmission in guinea pig model, thus we are going to study on the molecule mechanism why HB93 is not airborne transmissible in the guinea pig model.…”

A Replication-Defective Influenza Virus Vaccine Confers Complete Protection against H7N9 Viral Infection in Mice

“…Of the two main types of vaccines available for H7N9 infection, which include the inactivated influenza vaccine (IIV) and the live attenuated influenza vaccine (LAIV), the H7 IIV was deemed safe but less immunogenic in animals and humans [9,10]. Conversely, the LAIV provides protection from H7N9 replication and transmission in mammals [11]. Research has shown that there are advantages LAIVs have over IIVs, such as enhanced protection rates, longer-lasting immune responses, and the ability to mimic a natural infection by stimulating the mucosal immune system.…”