Evaluation of the Immune Responses to and Cross-Protective Efficacy of Eurasian H7 Avian Influenza Viruses

Abstract

Due to increasing concerns about human infection by various H7 influenza viruses, including recent H7N9 viruses, we evaluated the genetic relationships and cross-protective efficacies of three different Eurasian H7 avian influenza viruses. Phylogenic and molecular analyses revealed that recent Eurasian H7 viruses can be separated into two different lineages, with relatively high amino acid identities within groups (94.8 to 98.8%) and low amino acid identities between groups (90.3 to 92.6%). immunization with representatives of each group revealed that while group-specific cross-reactivity was induced, cross-reactive hemagglutination inhibition (HI) titers were approximately 4-fold lower against heterologous group viruses than against homologous group viruses. Moreover, the group I (RgW109/06) vaccine protected 100% of immunized mice from various group I viruses, while only 20 to 40% of immunized mice survived lethal challenge with heterologous group II viruses and exhibited high viral titers in the lung. Moreover, while the group II (RgW478/14) vaccine also protected mice from lethal challenge with group II viruses, it failed to elicit cross-protection against group I viruses. However, it is noteworthy that vaccination with RgAnhui1/13, a virus of a sublineage of group I, cross-protected immunized mice against lethal challenge with both group I and II viruses and significantly attenuated lung viral titers. Interestingly, immune sera from RgAnhui1/13-vaccinated mice showed a broad neutralizing spectrum rather than the group-specific pattern observed with the other viruses. These results suggest that the recent human-infective H7N9 strain may be a candidate broad cross-protective vaccine for Eurasian H7 viruses. Genetic and phylogenic analyses have demonstrated that the Eurasian H7 viruses can be separated into at least two different lineages, both of which contain human-infective fatal H7 viruses, including the recent novel H7N9 viruses isolated in China since 2013. Due to the increasing concerns regarding the global public health risk posed by H7 viruses, we evaluated the genetic relationships between Eurasian H7 avian influenza viruses and the cross-protective efficacies of three different H7 viruses: W109/06 (group I), W478/14 (group II), and Anhui1/13 (a sublineage of group I). While each vaccine induced group-specific antibody responses and cross-protective efficacy, only Anhui1/13 was able to cross-protect immunized hosts against lethal challenge across groups. In fact, the Anhui1/13 virus induced not only cross-protection but also broad serum neutralizing antibody responses against both groups of viruses. This suggests that Anhui1/13-like H7N9 viruses may be viable vaccine candidates for broad protection against Eurasian H7 viruses.

Pan-Influenza A Protection by Prime–Boost Vaccination with Cold-Adapted Live-Attenuated Influenza Vaccine in a Mouse Model

“…However, it was reported that non-specific immunity against non-influenza respiratory viruses in children vaccinated with a live-attenuated influenza vaccine (LAIV) was short-lived with the duration of as long as 1−2 weeks ( 62 ). Furthermore, many animal studies on cross-protection by LAIVs have presented protection data by performing in vivo challenge at 2−4 weeks after the vaccination ( 11 , 17 , 33 , 63 , 64 ). Considering these observations, our experimental design of the challenge at 5 weeks days after the boosting vaccination cannot be explained by non-specific mechanism.…”

Adjuvantation of Influenza Vaccines to Induce Cross-Protective Immunity

“…Molecular epidemiology studies found that H5N1 viruses had evolved into different clades and subclades, and H7N9 viruses had evolved into distinct lineages [ 61 , 62 ]. Similar to the seasonal influenza vaccine, H5N1 and H7N9 vaccines alone lack the ability to induce cross-clade or cross-lineage immunity [ 59 , 63 ].…”

Vaccination with Consensus H7 Elicits Broadly Reactive and Protective Antibodies against Eurasian and North American Lineage H7 Viruses

“…Furthermore, to determine whether the four sequences could form a three-dimensional conformation, homology models of CH7-22, CH7-24, CH7-26, and CH7-28 were constructed in the SWISS-MODEL webserver. The antigenic sites of H7 HA COBRA were determined based on alignment with the A/Anhui/1/2013 (H7N9) sequence as described previously [23]. Colorization of five antigenic sites (A, B, C, D and E) in trimerized H7 protein was performed using PyMol.…”