Protection of Mice against Lethal Infection with Highly Pathogenic H7N7 Influenza A Virus by Using a Recombinant Low-Pathogenicity Vaccine Strain (original) (raw)
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Developments in Avian Influenza Virus Vaccines
Journal of Poultry Science, 2007
The serologically diverse influenza A viruses, although transmissible among various susceptible species, mostly infect avian species. Avian influenza viruses (AIV) are also notorious for adapting to mammalian species, including humans. Although eradication of commercial birds infected with AIV is the preferred method of control, the ever presence of potential avian migratory, reservoir species makes worldwide spread inevitable and vaccine development a high priority for poultry. Live, attenuated vaccine strategies are of concern because of the potential of AIV to mutate, through point mutations and/or reassortment of their segmented genome. Both live and the safer, killed vaccines are of concern because of competition of natural and vaccine antigens in critical diagnostic assays. Subunit vaccines, which allow for protein distinction for diagnostic purposes, may consist of purified AIV protein or genes that encode individual viral proteins. Most vaccines have targeted the virus hemagglutinin protein, which is responsible for induction of the most e#ective neutralizing antibodies. Gene vaccines that include plasmid DNA and viral vector delivery of AIV genes allow for endogenous in vivo amplification of protein within cells. While fowlpox virus vectors have been licensed and proven to be e$cacious even in field situations, other viral vectors that target the respiratory tract are in experimental development with promising practical application for poultry. Maximum exploitation of vectored vaccines may incorporate enhancing immune molecules.
Avirulent Avian Influenza Virus as a Vaccine Strain against a Potential Human Pandemic
Journal of Virology, 1999
In the influenza H5N1 virus incident in Hong Kong in 1997, viruses that are closely related to H5N1 viruses initially isolated in a severe outbreak of avian influenza in chickens were isolated from humans, signaling the possibility of an incipient pandemic. However, it was not possible to prepare a vaccine against the virus in the conventional embryonated egg system because of the lethality of the virus for chicken embryos and the high level of biosafety therefore required for vaccine production. Alternative approaches, including an avirulent H5N4 virus isolated from a migratory duck as a surrogate virus, H5N1 virus as a reassortant with avian virus H3N1 and an avirulent recombinant H5N1 virus generated by reverse genetics, have been explored. All vaccines were formalin inactivated. Intraperitoneal immunization of mice with each of vaccines elicited the production of hemagglutination-inhibiting and virus-neutralizing antibodies, while intranasal vaccination without adjuvant induced ...
npj Vaccines
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 ...
Avian diseases, 2014
In the spring of 2012 an outbreak of H7N3 highly pathogenic (HP) avian influenza virus (AIV) occurred in poultry in Mexico. Vaccination was implemented as a control measure, along with increased biosecurity and surveillance. At that time there was no commercially available H7 AIV vaccine in North America; therefore, a recent H7N3 wild bird isolate of low pathogenicity from Mexico (A/cinnamon teal/Mexico/2817/2006 H7N3) was selected and utilized as the vaccine seed strain. In these studies, the potency and efficacy of this vaccine strain was evaluated in chickens against challenge with the 2012 Jalisco H7N3 HPAIV. Although vaccine doses of 256 and 102 hemagglutinating units (HAU) per bird decreased morbidity and mortality significantly compared to sham vaccinates, a dose of 512 HAU per bird was required to prevent mortality and morbidity completely. Additionally, the efficacy of 11 other H7 AIV vaccines and an antigenic map of hemagglutination inhibition assay data with all the vacci...
Clinical and Vaccine Immunology, 2013
In this study, we assessed in humans the immunogenicity and safety of one dose (7.5 or 15 g of hemagglutinin [HA]) of a whole-virion inactivated prepandemic influenza vaccine adjuvanted with aluminum hydroxide. The vaccine strain was made by reverse genetics from the highly pathogenic avian A/Chicken/Astana/6/05 (H5N1) clade 2.2 strain isolated from a dead bird in Kazakhstan. The humoral immune response was evaluated after a single vaccination by hemagglutination inhibition (HI) and microneutralization (MN) assays. The vaccine was safe and immunogenic, inducing seroconversion in 55% of the evaluated patients, with a geometric mean titer (GMT) of 17.1 and a geometric mean increase (GMI) of 3.42 after a dose of 7.5 g in the HI test against the vaccine strain. The rate of seroconversion increased up to 70% when the dose of 15 g was used. The percentages of individuals achieving anti-HA titers of >1:40 were 52.5% and 57.5% for the 7.5-and 15-g dose groups, respectively. Similar results were obtained when antibodies were analyzed in an MN test. Substantial cross-neutralization titers (seroconversion in 35% and 52.5% of subjects in the two dose groups, respectively) were detected against heterologous clade 1 strain NIBRG14 (H5N1). Thus, one dose of this whole-virion prepandemic vaccine adjuvanted with aluminum has the potential to be effective against H5N1 viruses of different clades.
Immune Control of Avian Influenza Virus Infection and Its Vaccine Development
Vaccines
The avian influenza A virus (AIV) is naturally prevalent in aquatic birds, infecting different avian species and transmitting from birds to humans. Both AIVs, the H5N1 and H7N9 viruses, have the potential to infect humans, causing an acute influenza disease syndrome in humans, and are a possible pandemic threat. AIV H5N1 is highly pathogenic, whereas AIV H7N9 has comparatively low pathogenicity. A clear insight into the disease pathogenesis is significant to understand the host’s immunological response, which in turn facilitates the design of the control and prevention strategies. In this review, we aim to provide comprehensive details on the pathogenesis and clinical features of the disease. Moreover, the innate and adaptive immunological responses to AIV and the recent studies conducted on the CD8+ T cell immunity against AIVs are detailed upon. Further, the current status and advancement in the development of AIV vaccines, along with the challenges, are also discussed. The inform...
Recombinant Influenza A Virus Vaccines for the Pathogenic Human A/Hong Kong/97 (H5N1) Viruses
The Journal of Infectious Diseases, 1999
Recombinant reassortment technology was used to prepare H5N1 influenza vaccine strains containing a modified hemagglutinin (HA) gene and neuraminidase gene from the A/Hong Kong/156/97 and A/Hong Kong/483/97 isolates and the internal genes from the attenuated cold-adapted A/Ann Arbor/6/60 influenza virus strain. The HA cleavage site (HA1/HA2) of each H5N1 isolate was modified to resemble that of "low-pathogenic" avian strains. Five of 6 basic amino acids at the cleavage site were deleted, and a threonine was added upstream of the remaining arginine. The H5 HA cleavage site modification resulted in the expected trypsin-dependent phenotype without altering the antigenic character of the H5 HA molecule. The temperature-sensitive and cold-adapted phenotype of the attenuated parent virus was maintained in the recombinant strains, and they grew to 10 8.5-9.4 EID 50 /mL in eggs. Both H5N1 vaccine virus strains were safe and immunogenic in ferrets and protected chickens against wild-type H5N1 virus challenge.
Journal of virology, 2017
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. Mo...