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J Virol. 2017 Mar 22. pii: JVI.02259-16. doi: 10.1128/JVI.02259-16. [Epub ahead of print]
Evaluation of the immune responses to and cross-protective efficacy of Eurasian H7 avian influenza viruses.
Kwon HI1,2, Kim YI1,2, Park SJ1,2, Song MS1,2, Kim EH1,2, Kim SM1,2, Si YJ1,2, Lee IW1, Song BM3, Lee YJ3, Yun SJ1, Kim WJ1, Choi YK4,2.
Author information
Abstract
Due to increasing concerns of human infection by various H7 viruses, including recent H7N9 viruses, we evaluated the genetic relationships and the cross-protective efficacies of three different Eurasian H7 avian influenza viruses. Phylogenic and molecular analysis revealed that recent Eurasian H7 viruses can be separated into two different lineages with relatively high amino acid identity within groups (94.8 to 98.8%), and low amino acid identity (90.3 to 92.6 %) between the groups. In vivo immunization with representatives of each group revealed that while group-specific cross-reactivity was induced, cross-reactive HI titers were approximately fourfold lower against heterologous group viruses compared to homologous group viruses. Moreover, the group I (RgW109/06) vaccine could protect 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 could also protect from lethal challenge with group II viruses, it failed to elicit cross-protection against group I viruses in mice. However, it is noteworthy that vaccination with RgAnhui1/13, which is 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 infectious H7N9 strain could be a candidate, broad cross-protective vaccine for Eurasian H7 viruses.IMPORTANCE 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 infectious, 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 efficacy 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 not only induced 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.
Copyright ? 2017 American Society for Microbiology.
PMID: 28331080 DOI: 10.1128/JVI.02259-16
Evaluation of the immune responses to and cross-protective efficacy of Eurasian H7 avian influenza viruses.
Kwon HI1,2, Kim YI1,2, Park SJ1,2, Song MS1,2, Kim EH1,2, Kim SM1,2, Si YJ1,2, Lee IW1, Song BM3, Lee YJ3, Yun SJ1, Kim WJ1, Choi YK4,2.
Author information
Abstract
Due to increasing concerns of human infection by various H7 viruses, including recent H7N9 viruses, we evaluated the genetic relationships and the cross-protective efficacies of three different Eurasian H7 avian influenza viruses. Phylogenic and molecular analysis revealed that recent Eurasian H7 viruses can be separated into two different lineages with relatively high amino acid identity within groups (94.8 to 98.8%), and low amino acid identity (90.3 to 92.6 %) between the groups. In vivo immunization with representatives of each group revealed that while group-specific cross-reactivity was induced, cross-reactive HI titers were approximately fourfold lower against heterologous group viruses compared to homologous group viruses. Moreover, the group I (RgW109/06) vaccine could protect 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 could also protect from lethal challenge with group II viruses, it failed to elicit cross-protection against group I viruses in mice. However, it is noteworthy that vaccination with RgAnhui1/13, which is 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 infectious H7N9 strain could be a candidate, broad cross-protective vaccine for Eurasian H7 viruses.IMPORTANCE 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 infectious, 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 efficacy 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 not only induced 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.
Copyright ? 2017 American Society for Microbiology.
PMID: 28331080 DOI: 10.1128/JVI.02259-16