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A modified live bat influenza A virus-based vaccine prototype provides full protection against HPAIV H5N1.

ABSTRACT: Highly pathogenic avian influenza viruses (HPAIVs) of subtype H5 are a major threat for poultry holdings worldwide, here especially the zoonotic Asian H5N1 viruses. These HPAIVs have caused more than 500 fatal spillover infections from poultry to humans, with a looming danger of a new pandemic by establishing human-to-human transmissions. Besides culling measures in infected farms in endemic areas, vaccination is the major tool against HPAIV. However, the mainly used inactivated preparations have several limitations, like application to the individual animal by injection and a reduced efficiency. Here we present a modified live influenza vaccine prototype, which is based on the H17N10 bat influenza virus. The new chimeric vaccine strain R65_mono/H17N10 was able to provide full protection against a lethal challenge infection with HPAIV H5N1 of juvenile and subadult chickens, as well as ferrets after oronasal immunization. In addition, the H5 vaccine prototype cannot reassort with avian influenza viruses and therefore is a promising tool against HPAIV H5 infection, allowing new vaccination strategies for efficient disease control.

SUBMITTER: Schon J

PROVIDER: S-EPMC7229168 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A modified live bat influenza A virus-based vaccine prototype provides full protection against HPAIV H5N1.

Schön Jacob J Ran Wei W Gorka Marco M Schwemmle Martin M Beer Martin M Hoffmann Donata D

NPJ vaccines 20200515 1

Highly pathogenic avian influenza viruses (HPAIVs) of subtype H5 are a major threat for poultry holdings worldwide, here especially the zoonotic Asian H5N1 viruses. These HPAIVs have caused more than 500 fatal spillover infections from poultry to humans, with a looming danger of a new pandemic by establishing human-to-human transmissions. Besides culling measures in infected farms in endemic areas, vaccination is the major tool against HPAIV. However, the mainly used inactivated preparations hav ...[more]

PMID: 32435514

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Project description:Recurring epizootic influenza A virus (IAV) infections in domestic livestock such as swine and poultry are associated with a substantial economic burden and pose a constant threat to human health. Therefore, universally applicable and safe animal vaccines are urgently needed. We recently demonstrated that a reassortment-incompatible chimeric bat H17N10 virus harboring the A/swan/Germany/R65/2006 (H5N1) surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) can be efficiently used as a modified live influenza vaccine (MLIV). To ensure vaccine safety and, thus, improve the applicability of this novel MLIV for mammalian usage, we performed consecutive passaging in eggs and chickens. Following passaging, we identified mutations in the viral polymerase subunits PB2 (I382S), PB1 (Q694H and I695K), and PA (E141K). Strikingly, recombinant chimeric viruses encoding these mutations showed no growth deficiencies in avian cells but displayed impaired growth in human cells and mice. Homologous prime-boost immunization of mice with one of these avian-adapted chimeric viruses, designated rR65mono/H17N10EP18, elicited a strong neutralizing antibody response and conferred full protection against lethal highly pathogenic avian influenza virus (HPAIV) H5N1 challenge infection. Importantly, the insertion of the avian-adaptive mutations into the conventional avian-like A/SC35M/1980 (H7N7) and prototypic human A/PR/8/34 (H1N1) viruses led to attenuated viral growth in human cells and mice. Collectively, our data show that the polymerase mutations identified here can be utilized to further improve the safety of our novel H17N10-based MLIV candidates for future mammalian applications. IMPORTANCE Recurring influenza A virus outbreaks in livestock, particularly in swine and chickens, pose a constant threat to humans. Live attenuated influenza vaccines (LAIVs) might be a potent tool to prevent epizootic outbreaks and the resulting human IAV infections; however, LAIVs have several disadvantages, especially in terms of reassortment with circulating IAVs. Notably, the newly identified bat influenza A viruses H17N10 and H18N11 cannot reassort with conventional IAVs. Chimeric bat influenza A viruses encoding surface glycoproteins of conventional IAV subtypes might thus function as safe and applicable modified live influenza vaccines (MLIVs).

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A modified live bat influenza A virus-based vaccine prototype provides full protection against HPAIV H5N1.

Publications

A modified live bat influenza A virus-based vaccine prototype provides full protection against HPAIV H5N1.

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