A highly immunogenic vaccine against A/H7N9 influenza virus

Cao, Weiping; Liepkalns, Justine S.; Hassan, Ahmed O.; Kamal, Ram P.; Hofstetter, Amelia R.; Amoah, Samuel; Kim, Jin Hyang; Reber, A.; Stevens, James; Katz, Jacqueline M.; Gangappa, Shivaprakash; York, Ian A.; Mittal, Suresh K.; Sambhara, Suryaprakash

doi:10.1016/j.vaccine.2015.12.062

Cited by 13 publications

(11 citation statements)

References 16 publications

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“…Three weeks following the booster inoculation, serum samples were collected and assayed for M2e-, HαD-, or HFD-specific IgG by ELISA (Fig 2). In this study, we did not monitor the immunogenicity of the prime dose (single inoculation prior to the second dose of the vaccine); however, it seems that the immunization of mice with a single dose of Ad vector-based vaccine elicited protective immune responses, and the second inoculation resulted in measurable increases in immunogen-specific immune responses [56]. …”

Section: Resultsmentioning

confidence: 99%

Adenovirus vector-based multi-epitope vaccine provides partial protection against H5, H7, and H9 avian influenza viruses

et al. 2017

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The emergence of H5, H7, and H9 avian influenza virus subtypes in humans reveals their pandemic potential. Although human-to-human transmission has been limited, the genetic reassortment of the avian and human/porcine influenza viruses or mutations in some of the genes resulting in virus replication in the upper respiratory tract of humans could generate novel pandemic influenza viruses. Current vaccines do not provide cross protection against antigenically distinct strains of the H5, H7, and H9 influenza viruses. Therefore, newer vaccine approaches are needed to overcome these potential threats. We developed an egg-independent, adenovirus vector-based, multi-epitope (ME) vaccine approach using the relatively conserved immunogenic domains of the H5N1 influenza virus [M2 ectodomain (M2e), hemagglutinin (HA) fusion domain (HFD), T-cell epitope of nucleoprotein (TNP). and HA α-helix domain (HαD)]. Our ME vaccine induced humoral and cell-mediated immune responses and caused a significant reduction in the viral loads in the lungs of vaccinated mice that were challenged with antigenically distinct H5, H7, or H9 avian influenza viruses. These results suggest that our ME vaccine approach provided broad protection against the avian influenza viruses. Further improvement of this vaccine will lead to a pre-pandemic vaccine that may lower morbidity, hinder transmission, and prevent mortality in a pandemic situation before a strain-matched vaccine becomes available.

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Section: Resultsmentioning

confidence: 99%

Adenovirus vector-based multi-epitope vaccine provides partial protection against H5, H7, and H9 avian influenza viruses

et al. 2017

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“…Due to the low immunogenicity of H7N9 candidate vaccines [14][15][16], there have been several efforts to improve vaccine efficacy. The adaptation of the H7N9 vaccine virus by serial passaging in MDCK cells [33] and by using an adenoviral vector [34] are https://doi.org/10.1371/journal.pbio.3001024.g003…”

Section: Discussionmentioning

confidence: 99%

“…Due to the low immunogenicity of H7N9 candidate vaccines [ 14 – 16 ], there have been several efforts to improve vaccine efficacy. The adaptation of the H7N9 vaccine virus by serial passaging in MDCK cells [ 33 ] and by using an adenoviral vector [ 34 ] are examples of such efforts, despite the setbacks of these approaches, such as the appearance of multiple mutations in various viral protein-encoding regions during adaptation and the hurdle of obtaining clinical approval for DNA vaccine constructs. To overcome these issues, we tested an HA NLG modification strategy [ 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

Glycosylation generates an efficacious and immunogenic vaccine against H7N9 influenza virus

et al. 2020

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Zoonotic avian influenza viruses pose severe health threats to humans. Of several viral subtypes reported, the low pathogenic avian influenza H7N9 virus has since February 2013 caused more than 1,500 cases of human infection with an almost 40% case-fatality rate. Vaccination of poultry appears to reduce human infections. However, the emergence of highly pathogenic strains has increased concerns about H7N9 pandemics. To develop an efficacious H7N9 human vaccine, we designed vaccine viruses by changing the patterns of N-linked glycosylation (NLG) on the viral hemagglutinin (HA) protein based on evolutionary patterns of H7 HA NLG changes. Notably, a virus in which 2 NLG modifications were added to HA showed higher growth rates in cell culture and elicited more cross-reactive antibodies than did other vaccine viruses with no change in the viral antigenicity. Developed into an inactivated vaccine formulation, the vaccine virus with 2 HA NLG additions exhibited much better protective efficacy against lethal viral challenge in mice than did a vaccine candidate with wild-type (WT) HA by reducing viral replication in the lungs. In a ferret model, the 2 NLG-added vaccine viruses also induced hemagglutination-inhibiting antibodies and significantly suppressed viral replication in the upper and lower respiratory tracts compared with the WT HA vaccines. In a mode of action study, the HA NLG modification appeared to increase HA protein contents incorporated into viral particles, which would be successfully translated to improve vaccine efficacy. These results suggest the strong potential of HA NLG modifications in designing avian influenza vaccines.

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“…One MVA vector expressing the HA from H7N9 A/Shanghai/2/2013 was shown to be immunogenic and protective in a ferret model of pneumonia 14 . In addition to an MVA vector approach, other viral vector vaccines for protection against H7 viruses have been reported 31 , 32 as well as live attenuated H7 vaccines 33 , 34 . All of the H7 virus vectors and inactivated H7 vaccines to date have focused on the immunogenicity and protective effect of H7 HA.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity and Protection Against Influenza H7N3 in Mice by Modified Vaccinia Virus Ankara Vectors Expressing Influenza Virus Hemagglutinin or Neuraminidase

Meseda

Atukorale

Soto

et al. 2018

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Influenza subtypes such as H7 have pandemic potential since they are able to infect humans with severe consequences, as evidenced by the ongoing H7N9 infections in China that began in 2013. The diversity of H7 viruses calls for a broadly cross-protective vaccine for protection. We describe the construction of recombinant modified vaccinia virus Ankara (MVA) vectors expressing the hemagglutinin (HA) or neuraminidase (NA) from three H7 viruses representing both Eurasian and North American H7 lineages – A/mallard/Netherlands/12/2000 (H7N3), A/Canada/rv444/2004 (H7N3), and A/Shanghai/02/2013 (H7N9). These vectors were evaluated for immunogenicity and protective efficacy against H7N3 virus in a murine model of intranasal challenge. High levels of H7-, N3-, and N9-specific antibodies, including neutralizing antibodies, were induced by the MVA-HA and MVA-NA vectors. Mice vaccinated with MVA vectors expressing any of the H7 antigens were protected, suggesting cross-protection among H7 viruses. In addition, MVA vectors expressing N3 but not N9 elicited protection against H7N3 virus challenge. Similar outcomes were obtained when immune sera from MVA vector-immunized mice were passively transferred to naïve mice prior to challenge with the H7N3 virus. The results support the further development of an MVA vector platform as a candidate vaccine for influenza strains with pandemic potential.

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A highly immunogenic vaccine against A/H7N9 influenza virus

Cited by 13 publications

References 16 publications

Adenovirus vector-based multi-epitope vaccine provides partial protection against H5, H7, and H9 avian influenza viruses

Adenovirus vector-based multi-epitope vaccine provides partial protection against H5, H7, and H9 avian influenza viruses

Glycosylation generates an efficacious and immunogenic vaccine against H7N9 influenza virus

Immunogenicity and Protection Against Influenza H7N3 in Mice by Modified Vaccinia Virus Ankara Vectors Expressing Influenza Virus Hemagglutinin or Neuraminidase

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