Low Pathogenic Avian Influenza H7 Research Articles

Highly pathogenic avian influenza A/Guangdong/17SF003/2016 is immunogenic and induces cross-protection against antigenically divergent H7N9 viruses

Avian influenza A(H7N9) epidemics have a fatality rate of approximately 40%. Previous studies reported that low pathogenic avian influenza (LPAI)-derived candidate vaccine viruses (CVVs) are poorly immunogenic. Here, we assess the immunogenicity and efficacy of a highly pathogenic avian influenza (HPAI) A/Guangdong/17SF003/2016 (GD/16)-extracted hemagglutinin (eHA) vaccine. GD/16 eHA induces robust H7-specific antibody responses in mice with a marked adjuvant antigen-sparing effect. Mice immunized with adjuvanted GD/16 eHA are protected from the lethal LPAI and HPAI H7N9 challenges, in stark contrast to low antibody titers and high mortality in mice receiving adjuvanted LPAI H7 eHAs. The protection correlates well with the magnitude of the H7-specific antibody response (IgG and microneutralization) or HA group 2 stem-specific IgG. Inclusion of adjuvanted GD/16 eHA in heterologous prime-boost improves the immunogenicity and protection of LPAI H7 HAs in mice. Our findings support the inclusion of GD/16-derived CVV in the pandemic preparedness vaccine stockpile.

Mammalian pathogenicity and transmissibility of low pathogenic avian influenza H7N1 and H7N3 viruses isolated from North America in 2018

ABSTRACT Low pathogenic avian influenza (LPAI) H7 subtype viruses are infrequently, but persistently, associated with outbreaks in poultry in North America. These LPAI outbreaks provide opportunities for the virus to develop enhanced virulence and transmissibility in mammals and have previously resulted in both occasional acquisition of a highly pathogenic avian influenza (HPAI) phenotype in birds and sporadic cases of human infection. Two notable LPAI H7 subtype viruses caused outbreaks in 2018 in North America: LPAI H7N1 virus in chickens and turkeys, representing the first confirmed H7N1 infection in poultry farms in the United States, and LPAI H7N3 virus in turkeys, a virus subtype often associated with LPAI-to-HPAI phenotypes. Here, we investigated the replication capacity of representative viruses from these outbreaks in human respiratory tract cells and mammalian pathogenicity and transmissibility in the mouse and ferret models. We found that the LPAI H7 viruses replicated to high titre in human cells, reaching mean peak titres generally comparable to HPAI H7 viruses. Replication was efficient in both mammalian species, causing mild infection, with virus primarily limited to respiratory tract tissues. The H7 viruses demonstrated a capacity to transmit to naïve ferrets in a direct contact setting. These data support the need to perform routine risk assessments of LPAI H7 subtype viruses, even in the absence of confirmed human infection.

The production and development of H7 Influenza virus pseudotypes for the study of humoral responses against avian viruses

In recent years, high pathogenicity avian influenza (HPAI) virus, H5N1, low pathogenicity avian influenza (LPAI) virus, H9N2, and both HPAI and LPAI H7 viruses have proved devastating for the affected economies reliant on poultry industry, and have posed serious public health concerns. These viruses have repeatedly caused zoonotic disease in humans, raising concerns of a potential influenza pandemic. Despite the focus on the HPAI H5N1 outbreak in 1997 some H7 strains have also shown to be occasionally adaptable to infecting humans. Therefore, applying knowledge of the H5 virus evolution and spread to the development of sensitive serological methods is likely to improve our ability to understand and respond to the emergence of other HPAI and LPAI viruses, present within the avian populations, with the potential to infect humans and other species. In the present study we describe the construction and production of lentiviral pseudotypes bearing envelope glycoproteins of LPAI and HPAI H7 avian influenza viruses, which have been responsible for several outbreaks in the past decade. The H7 pseudotypes were evaluated in pseudotype-based neutralization (pp-NT) assays in order to detect and quantify the presence of neutralizing antibodies in avian sera, which were confirmed H7 positive by inhibition of haemagglutination (HI) test. Overall, our results substantiate influenza virus pseudotype neutralization as a robust tool for influenza sero-surveillance.

Low pathogenic H7 subtype avian influenza viruses isolated from domestic ducks in South Korea and the close association with isolates of wild birds

We characterized low pathogenic avian influenza (LPAI) viruses of the H7 subtype that were isolated from domestic ducks and wild birds in South Korea from 2008 to 2011. A total of 20 H7 viruses were collected from live-bird markets (LBMs), duck farms and wild-bird habitats using avian influenza (AI) surveillance and epidemiological approaches. A phylogenetic analysis of the H7 viruses that were isolated from domestic ducks and wild birds demonstrated that they were separated into 12 genotypes (A-D and Wb-1-8, respectively), indicating genetic diversity. These H7 viruses were related to the recently isolated Eurasian LPAI H7 viruses and various influenza viruses that are circulating in Asia, including southern China and South Korea. The same genotype was not found between domestic poultry and wild-bird isolates; however, most of the H7 viruses in poultry (genotypes B and C) were closely related to the H7 virus isolated from a wild bird (genotype Wb-3). Animal-challenge studies revealed that certain H7 AI viruses replicated well only in chickens or ducks depending on the genotype, indicating that the pathogenicity of H7 viruses has the potential to be altered due to multiple reassortments, and these viruses can potentially expand their host range. Our results are evidence of abundant and frequent reassortment between H7 viruses in poultry and wild birds and emphasize the continuing need to monitor the evolutionary genetics of the influenza virus in poultry and wild birds.

Surveillance for Avian Influenza in Wild Birds in the European Union in 2007

Surveillance of wild birds for avian influenza viruses has been compulsory in the European Union (EU) since 2005, primarily as a means of detecting H5N1 highly pathogenic avian influenza (HPAI) virus and of monitoring the circulation of low pathogenicity avian influenza (LPAI) virus H5 and H7 strains. In 2007, 79,392 wild birds were tested throughout the EU. H5N1 HPAI was detected in 329 birds from four Member States (MS); affected birds were almost entirely of the orders Podicipediformes (grebes) and Anseriformes (waterfowl) during the summer months. LPAI was detected in 1485 wild birds among 21 MS. A total of 1250 birds were positive for influenza A but were not discriminated any further; LPAI H5 was detected in 105 birds, exclusively of the order Anseriformes. LPAI H7 was detected in seven birds. LPAI of other subtypes was found in 123 birds. Epidemiologic evidence and phylogenetic analysis of H5N1 viruses indicate that H5N1 did not appear to persist in the EU from 2006 but was reintroduced, probably from the Middle East.

Avian influenza viruses in humans

Past pandemics arose from low pathogenic avian influenza (LPAI) viruses. In more recent times, highly pathogenic avian influenza (HPAI) H5N1, LPAI H9N2 and both HPAI and LPAI H7 viruses have repeatedly caused zoonotic disease in humans. Such infections did not lead to sustained human-to-human transmission. Experimental infection of human volunteers and seroepidemiological studies suggest that avian influenza viruses of other subtypes may also infect humans. Viruses of the H7 subtype appear to have a predilection to cause conjunctivitis and influenza-like illness (ILI), although HPAI H7N7 virus has also caused fatal respiratory disease. Low pathogenic H9N2 viruses have caused mild ILI and its occurrence may be under-recognised for this reason. In contrast, contemporary HPAI H5N1 viruses are exceptional in their virulence for humans and differ from human seasonal influenza viruses in their pathogenesis. Patients have a primary viral pneumonia progressing to acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome. Over 380 human cases have been confirmed to date, with an overall case fatality of 63%. The zoonotic transmission of avian influenza is a rare occurrence, butthe greater public health concern is the adaptation of such viruses to efficient human transmission, which could lead to a pandemic. A better understanding of the ecology of avian influenza viruses and the biological determinants of transmissibility and pathogenicity in humans is important for pandemic preparedness.