Innate immunemodulator containing adjuvant formulated HA based vaccine protects mice from lethal infection of highly pathogenic avian influenza H5N1 virus

Lu, Yao; Landreth, Shelby; Liu, Guanqun; Brownlie, Robert; Gaba, Amit; Hurk, Sylvia van Drunen Littel‐van den; Gerdts, Volker; Zhou, Yan

doi:10.1016/j.vaccine.2020.01.051

Cited by 9 publications

(7 citation statements)

References 39 publications

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“…The continuous evolution and mutation of the H7N9 avian influenza virus poses a dual threat to human health and the poultry industry (4), and thus it is imperative to develop a safe and effective vaccine against H7N9 virus infections. A variety of the influenza vaccine formations were designed to protect against influenza virus (35)(36)(37)(38). Avian influenza VLPs retain the structural and antigenic properties of native viruses but lack the genetic material, which is a better selection as vaccine antigen for the development of influenza vaccine.…”

Section: Discussionmentioning

confidence: 99%

Supplementation of H7N9 Virus-Like Particle Vaccine With Recombinant Epitope Antigen Confers Full Protection Against Antigenically Divergent H7N9 Virus in Chickens

Kong

Chen

et al. 2022

Front. Immunol.

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The continuous evolution of the H7N9 avian influenza virus suggests a potential outbreak of an H7N9 pandemic. Therefore, to prevent a potential epidemic of the H7N9 influenza virus, it is necessary to develop an effective crossprotective influenza vaccine. In this study, we developed H7N9 virus-like particles (VLPs) containing HA, NA, and M1 proteins derived from H7N9/16876 virus and a helper antigen HMN based on influenza conserved epitopes using a baculovirus expression vector system (BEVS). The results showed that the influenza VLP vaccine induced a strong HI antibody response and provided effective protection comparable with the effects of commercial inactivated H7N9 vaccines against homologous H7N9 virus challenge in chickens. Meanwhile, the H7N9 VLP vaccine induced robust crossreactive HI and neutralizing antibody titers against antigenically divergent H7N9 viruses isolated in wave 5 and conferred on chickens complete clinical protection against heterologous H7N9 virus challenge, significantly inhibiting virus shedding in chickens. Importantly, supplemented vaccination with HMN antigen can enhance Th1 immune responses; virus shedding was completely abolished in the vaccinated chickens. Our study also demonstrated that viral receptor-binding avidity should be taken into consideration in evaluating an H7N9 candidate vaccine. These studies suggested that supplementing influenza VLP vaccine with recombinant epitope antigen will be a promising strategy for the development of broad-spectrum influenza vaccines.

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Section: Discussionmentioning

confidence: 99%

Supplementation of H7N9 Virus-Like Particle Vaccine With Recombinant Epitope Antigen Confers Full Protection Against Antigenically Divergent H7N9 Virus in Chickens

Kong

Chen

et al. 2022

Front. Immunol.

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“…Multiscreen-HA plates, 0.45 µM, sterile (Millipore, MAHAS4510) were coated with either purified rat anti-mouse IFN-γ (BD, 551216) or purified rat anti-mouse IL-5 (BD, 554393) overnight at 4 • C. Mouse splenocytes were seeded at 5 × 10 5 cells/well and were stimulated for 20 h at 37 • C with 50 µg/mL of either the purified β-propiolactone-inactivated rWT virus or medium only in triplicate. The spots were developed as described previously, and counted with the ELISPOT reader (AID, Strassberg, Germany) [20]. The data reported is presented as the number of IFN-γ and IL-5-secreting cells per 5 × 10 5 cells with the number of spots in the medium-only wells subtracted as background.…”

Section: Detection Of Ifn-γ and Il-5 Secreting Cells By Enzyme-linkedmentioning

confidence: 99%

“…The hemagglutination inhibition (HAI) and serum viral neutralization (SVN) assays were conducted according to a previous report [20]. Four HA units of BC15 (H7N9) were used in the HAI assay.…”

Section: Hemagglutination Inhibition (Hai) and The Serum Viral Neutramentioning

confidence: 99%

A Replication-Defective Influenza Virus Vaccine Confers Complete Protection against H7N9 Viral Infection in Mice

Landreth

Pandey

et al. 2020

Vaccines

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Avian influenza H7N9 viruses continue to pose a great threat to public health, which is evident by their high case-fatality rates. Although H7N9 was first isolated in humans in China in 2013, to date, there is no commercial vaccine available against this particular strain. Our previous studies developed a replication-defective influenza virus through mutation of the hemagglutinin (HA) cleavage site from a trypsin-sensitive to an elastase-sensitive motif. In this study, we report the development of a reassortant mutant influenza virus derived from the human isolate A/British Columbia/01/2015 (H7N9) [BC15 (H7N9)], which is the QVT virus. The HA gene of this virus possesses three mutations at the cleavage site, Lys-Gly-Arg were mutated to Gln-Thr-Val at amino acid (aa) positions 337, 338, and 339, respectively. We report this virus to rely on elastase in vitro, possess unaltered replication abilities when elastase was provided compared to the wild type virus in vitro, and to be non-virulent and replication-defective in mice. In addition, we report this virus to induce significant levels of antibodies and IFN-γ and IL-5 secreting cells, and to protect mice against a lethal challenge of the BC15 (H7N9) virus. This protection is demonstrated through the lack of body weight loss, 100% survival rate, and the prevention of BC15 (H7N9) viral replication as well as the reduction of proinflammatory cytokines induced in the mouse lung associated with the influenza disease. Therefore, these results provide strong evidence for the use of this reassortant mutant H7N9 virus as a replication-defective virus vaccine candidate against H7N9 viruses.

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“…HA is the primary target antigen for eliciting serological immunity to the influenza virus [ 16 ]. HA is used to develop influenza subunit vaccines and has been shown to induce excellent protection against influenza virus infection in addition to the H5 serotype because H5 HA is a weak antigen [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

A single immunization with H5N1 virus-like particle vaccine protects chickens against divergent H5N1 influenza viruses and vaccine efficacy is determined by adjuvant and dosage

Kong,

He,

Wang

et al. 2023

Emerging Microbes & Infections

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The H5N1 subtype highly pathogenic avian influenza virus (HPAIV) reveals high variability and threatens poultry production and public health. To prevent the spread of H5N1 HPAIV, we developed an H5N1 virus-like particle (VLP) vaccine based on the insect cell-baculovirus expression system. Single immunization of the H5N1 VLP vaccines induced high levels of HI antibody titres and provided effective protection against homologous virus challenge comparable to the commercial inactivated vaccine. Meanwhile, we assessed the relative efﬁcacy of different adjuvants by carrying out a head-to-head comparison of the adjuvants ISA 201 and ISA 71 and evaluated whether the two adjuvants could induce broadly protective immunity. The ISA 71 adjuvanted vaccine induced significantly higher levels of Th1 and Th2 immune responses and provided superior cross-protection against antigenically divergent H5N1 virus challenge than the ISA 201 adjuvanted vaccine. Importantly, increasing the vaccine dose could further enhance the cross-protective efficacy of H5N1 VLP vaccine and confer completely sterilizing protection against antigenically divergent H5N1 virus challenge, which was mediated by neutralizing antibodies. Our results suggest that the H5N1 VLP vaccine can provide broad-spectrum protection against divergent H5N1 influenza viruses as determined by adjuvant and vaccine dose.

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Innate immunemodulator containing adjuvant formulated HA based vaccine protects mice from lethal infection of highly pathogenic avian influenza H5N1 virus

Cited by 9 publications

References 39 publications

Supplementation of H7N9 Virus-Like Particle Vaccine With Recombinant Epitope Antigen Confers Full Protection Against Antigenically Divergent H7N9 Virus in Chickens

Supplementation of H7N9 Virus-Like Particle Vaccine With Recombinant Epitope Antigen Confers Full Protection Against Antigenically Divergent H7N9 Virus in Chickens

A Replication-Defective Influenza Virus Vaccine Confers Complete Protection against H7N9 Viral Infection in Mice

A single immunization with H5N1 virus-like particle vaccine protects chickens against divergent H5N1 influenza viruses and vaccine efficacy is determined by adjuvant and dosage

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