Evaluation of the Immune Responses to and Cross-Protective Efficacy of Eurasian H7 Avian Influenza Viruses.
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%).In vivoimmunization 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.IMPORTANCEGenetic 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.
College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.|Zoonotic Infectious Diseases Research Center, Chungbuk National University, Cheongju, Republic of Korea.
Hyeok-Il
HI
Kwon
College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.|Zoonotic Infectious Diseases Research Center, Chungbuk National University, Cheongju, Republic of Korea.
Young-Il
YI
Kim
College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.|Zoonotic Infectious Diseases Research Center, Chungbuk National University, Cheongju, Republic of Korea.
Su-Jin
SJ
Park
College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.|Zoonotic Infectious Diseases Research Center, Chungbuk National University, Cheongju, Republic of Korea.
Min-Suk
MS
Song
College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.|Zoonotic Infectious Diseases Research Center, Chungbuk National University, Cheongju, Republic of Korea.
Eun-Ha
EH
Kim
College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.|Zoonotic Infectious Diseases Research Center, Chungbuk National University, Cheongju, Republic of Korea.
Se Mi
SM
Kim
College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.|Zoonotic Infectious Diseases Research Center, Chungbuk National University, Cheongju, Republic of Korea.
Young-Jae
YJ
Si
College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.
In-Won
IW
Lee
Avian Disease Division, Animal and Plant Quarantine Agency, Gimcheon-si, Gyeongsangbuk-do, Republic of Korea.
Byung-Min
BM
Song
Avian Disease Division, Animal and Plant Quarantine Agency, Gimcheon-si, Gyeongsangbuk-do, Republic of Korea.
Youn-Jeong
YJ
Lee
College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.
Seok Joong
SJ
Yun
College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea.
Wun-Jae
WJ
Kim
College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea choiki55@chungbuk.ac.kr.|Zoonotic Infectious Diseases Research Center, Chungbuk National University, Cheongju, Republic of Korea.
Young Ki
YK
Choi
D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D056738:Cross Protection; D003429:Cross Reactions; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000821:virology; D008168:Lung / Q000821:virology; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D010802:Phylogeny; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000276:immunology
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated
Eurasian H7 influenza virus; H7N9; cross-reactivity; vaccines