Mono- and quadri-subtype virus-like particles (VLPs) containing H10 subtype elicit protective immunity to H10 influenza in a ferret challenge model

Pushko, Peter; Sun, Xiangjie; Tretyakova, Irina; Hidajat, Rachmat; Pulit-Penaloza, Joanna A.; Belser, Jessica A.; Maines, Taronna R.; Tumpey, Terrence M.

doi:10.1016/j.vaccine.2016.09.012

Cited by 8 publications

(20 citation statements)

References 45 publications

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“…4A). Also in agreement with our findings, on day 4 postinfection of ferrets with A/teal/Egypt/12908-NAMRU3/ 2005 (H10N1), titers of 10 7 and 10 3 EID 50 were detected in nasal turbinates and lungs, respectively (37). For studies using A/harbor seal/Germany/PV20762_TS/2014 (H10N7), animals were inoculated intratracheally, and viral replication was evaluated throughout the respiratory tract (32).…”

Section: Discussionsupporting

confidence: 74%

“…In previous studies, three H10 viruses were evaluated in ferrets. These isolates were tk/MN/79, A/teal/Egypt/12908-NAMRU3/2005 (H10N1), and A/harbor seal/Germany/ PV20762_TS/2014 (H10N7) (32,37,38). In studies with tk/MN/79, ferrets shed virus for 7 days, with a peak titer of 10 7.3 50% egg infective doses (EID 50 )/ml following intranasal inoculation (38).…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of the Biological Properties and Cross-Reactive Antibody Response to H10 Influenza Viruses in Ferrets

Sutton

Lamirande

Czakó

et al. 2017

J Virol

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The recent outbreak of avian origin H10N7 influenza among seals in Northern Europe, and two fatal human infections with an avian H10N8 virus in China, have demonstrated that H10 viruses can spread between mammals and cause severe disease in humans. To gain insight into the potential for H10 viruses to cross the species barrier and identify a candidate vaccine strain, we evaluated the in vitro and in vivo properties and antibody response in ferrets to 20 diverse H10 viruses. H10 virus infection of ferrets caused variable weight loss and all 20 viruses replicated throughout the respiratory tract; however, replication in the lungs was highly variable. In glycan-binding assays, the H10 viruses preferentially bound "avian-like" α2,3-linked sialic acids. Importantly, several isolates also displayed strong binding to long-chain "human-like" α2,6-linked sialic acids, and exhibited comparable or elevated neuraminidase activity relative to human H1N1, H2N2, and H3N2 viruses. In hemagglutination inhibition assays, 12 antisera cross-reacted with ≥ 14 of 20 H10 viruses, and 7 viruses induced neutralizing activity against ≥ 15 of the 20 viruses. By combining data on weight loss, viral replication, and the cross-reactive antibody response, we identified A/mallard/Portugal/79906/2009 (H10N7) as a suitable virus for vaccine development. Collectively, our findings suggest that H10 viruses may continue to sporadically infect humans and other mammals, underscoring the importance of developing an H10 vaccine for pandemic preparedness. Avian origin H10 influenza viruses sporadically infect humans and other mammals; however, little is known about viruses of this subtype. Thus, we characterized the biological properties of 20 H10 viruses in vitro and in ferrets. Infection caused mild to moderate weight loss (5-15%), with robust viral replication in the nasal tissues and variable replication in the lung. H10 viruses preferentially bind "avian-like" sialic acids, although several isolates also displayed binding to "human-like" sialic acid receptors. This is consistent with the ability of H10 viruses to cross the species barrier, and warrants selection of an H10 vaccine strain. By evaluating the cross-reactive antibody response to the H10 viruses, and combining this analysis with viral replication and weight loss findings, we identified A/mallard/Portugal/79906/2009 (H10N7) as a suitable H10 vaccine strain.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Evaluation of the Biological Properties and Cross-Reactive Antibody Response to H10 Influenza Viruses in Ferrets

Sutton

Lamirande

Czakó

et al. 2017

J Virol

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“…NA has been previously shown to be required for assembly and budding of VLPs (Chen et al, 2007); therefore, NA was included into VLPs. Bgag has been previously used for VLP preparation in place of influenza matrix protein (Kapczynski et al, 2016; Pushko et al, 2016; Tretyakova et al, 2016). To prepare VLPs, Sf9 cells were infected with rBV to allow expression and secretion of VLPs containing H5, H7, H9, N1, and Bgag proteins.…”

Section: Resultsmentioning

confidence: 99%

“…Recombinant VLPs comprised of hemagglutinin (HA), neuraminidase (NA) and matrix (M1) proteins have been described (Bright et al, 2007; Galarza et al, 2005; Kang et al, 2009; Perrone et al, 2009; Pushko et al, 2005; Quan et al; Ross et al, 2009). In some cases, retrovirus gag, such as bovine immunodeficiency virus gag (Bgag), has been used in place of M1 (Kapczynski et al, 2016; Pushko et al, 2016; Tretyakova et al, 2016). Bgag has the advantage of a larger diameter providing more surface area to accommodate multiple HA molecules (Tretyakova et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Virus-like particles displaying H5, H7, H9 hemagglutinins and N1 neuraminidase elicit protective immunity to heterologous avian influenza viruses in chickens

et al. 2017

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Avian influenza (AI) viruses circulating in wild birds pose a serious threat to public health. Human and veterinary vaccines against AI subtypes are needed. Here we prepared triple-subtype VLPs that co-localized H5, H7 and H9 antigens derived from H5N1, H7N3 and H9N2 viruses. VLPs also contained influenza N1 neuraminidase and retroviral gag protein. The H5/H7/H9/N1/gag VLPs were prepared using baculovirus expression. Biochemical, functional and antigenic characteristics were determined including hemagglutination and neuraminidase enzyme activities. VLPs were further evaluated in a chicken AI challenge model for safety, immunogenicity and protective efficacy against heterologous AI viruses including H5N2, H7N3 and H9N2 subtypes. All vaccinated birds survived challenges with H5N2 and H7N3 highly pathogenic AI (HPAI) viruses, while all controls died. Immune response was also detectable after challenge with low pathogenicity AI (LPAI) H9N2 virus suggesting that H5/H7/H9/N1/gag VLPs represent a promising approach for the development of broadly protective AI vaccine.

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“…30,31 However, concerns remain such as low production efficiency and potential cytotoxicity. Liposomes have shown a superior ability to deliver multiple antigens and adjuvants to the targeting sites, although their poor stability and loading efficiency limit their benefits in vaccination development.…”

mentioning

confidence: 99%

Dual-linker gold nanoparticles as adjuvanting carriers for multivalent display of recombinant influenza hemagglutinin trimers and flagellin improve the immunological responses in vivo and in vitro

Wang

Zhu

Wang

2017

IJN

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Vaccination is the most cost-effective means of infectious disease control. Although current influenza vaccines are effective in battling closely matched strains, such vaccines have major limitations such as the requirement to produce new vaccines every season, an egg-dependent production system, long production periods, uncertainty in matching the vaccine to circulating strains, and the inability to react to new influenza pandemics resulting from genetic drift or shift. To overcome the intrinsic limitations of the conventional influenza vaccine, we have designed dual-linker gold nanoparticles (AuNPs) conjugated with both recombinant trimetric A/Aichi/2/68 (H3N2), hemagglutinin (HA) and TLR5 agonist flagellin (FliC) as a novel vaccine approach. Click chemistry and metal-chelating reactions were used to couple the two proteins. The conjugated proteins were found to possess high coupling specificity, high stability in harsh environments, high conjugation efficiency, and the ability to keep the appropriate protein conformations for immunogenicity and immunostimulation. Both AuNPs-HA/FliC and AuNPs-HA formulations induced higher levels of antibody responses than a mixture of soluble HA and FliC proteins when administered via a single intranasal immunization in mice. To further investigate the adjuvancy of these nanoparticles, in vitro experiments were conducted in both the JAWS II dendritic cell (DC) line and bone marrow-derived DC (BMDC) models. The results showed that dual-conjugated AuNPs were rapidly targeted and taken up by DCs. Consequently, DCs were induced toward maturation, as demonstrated by high levels of cytokine secretions and membrane costimulatory molecule expression. T cell proliferation was observed when splenic T cells were cocultured with AuNPs-HA/FliC-primed BMDCs. These results suggest that dual-conjugated AuNPs are effective at simultaneously displaying antigens and adjuvants in an oriented, multivalent format and can promote a strong immune response by activating DCs and T cells.

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Mono- and quadri-subtype virus-like particles (VLPs) containing H10 subtype elicit protective immunity to H10 influenza in a ferret challenge model

Cited by 8 publications

References 45 publications

Evaluation of the Biological Properties and Cross-Reactive Antibody Response to H10 Influenza Viruses in Ferrets

Evaluation of the Biological Properties and Cross-Reactive Antibody Response to H10 Influenza Viruses in Ferrets

Virus-like particles displaying H5, H7, H9 hemagglutinins and N1 neuraminidase elicit protective immunity to heterologous avian influenza viruses in chickens

Dual-linker gold nanoparticles as adjuvanting carriers for multivalent display of recombinant influenza hemagglutinin trimers and flagellin improve the immunological responses in vivo and in vitro

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