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. 2020 May 15;5:40.
doi: 10.1038/s41541-020-0185-6. eCollection 2020.

A Modified Live Bat Influenza A Virus-Based Vaccine Prototype Provides Full Protection Against HPAIV H5N1

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Free PMC article

A Modified Live Bat Influenza A Virus-Based Vaccine Prototype Provides Full Protection Against HPAIV H5N1

Jacob Schön et al. NPJ Vaccines. .
Free PMC article

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 R65mono/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.

Keywords: Influenza virus; Live attenuated vaccines.

Conflict of interest statement

Competing interestsThe authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Percentage survival following R65mono/H17N10 immunization and subsequent homologous HPAIV challenge infection in chickens.
Groups of 4-weeks-old (subadult group) and 1-day-old (juvenile group) chickens were a immunized twice with R65mono/H17N10 MLIV candidate and b challenged with a homologous HPAIV. Five naive contact controls (sentinels) accompanied each group. Three naive controls served as negative-control and from d23 on as positive control to verify the challenge infection.
Fig. 2
Fig. 2. Monitoring of ferret weight and body temperature following R65mono/H17N10 immunization and subsequent homologous HPAIV challenge infection.
Rectal body temperature (normal range indicated with gray background—asterisks indicate elevated values) and relative body weight change following prime-boost vaccination (a, c), as well as following challenge infection (b, d).
Fig. 3
Fig. 3. Viral genome loads in swab and organ samples following immunization with R65mono/H17N10 MLIV and subsequent homologous HPAIV challenge infection.
We examined oropharyngeal swab samples in vaccinated chicken (a) and corresponding co-housing contacts (b) after prime-boost vaccination and after challenge infection (c, d). Organ samples were taken post-mortem on dpc7 (e, f). All samples were examined using pan-influenza PB1-sequence-specific RT-qPCR.
Fig. 4
Fig. 4. Viral genome loads in ferret nasal washing and organ samples, following immunization with R65mono/H17N10 MLIV, and subsequent homologous HPAIV challenge infection (CI).
Nasal washing samples were taken following prime-boost vaccination (a, b) and following the challenge infection (c, d). Organ samples (e, f) were taken post-mortem on dpc6 (positive control animal killed on dpc3). All samples were examined using pan-influenza PB1-sequence-specific RT-qPCR.
Fig. 5
Fig. 5. Humoral immune response to R65mono/H17N10 immunization and subsequent challenge infection in chickens.
Serum samples were taken from all animals on d0, d11, d23, and 7 days post challenge (dpc7 = d30), and evaluated using a competitive Enzyme-linked Immunosorbent Assay (ELISA) specific for nucleoprotein (NP) (a, b) or hemagglutinin H5 binding antibodies (c, d). Reduction of the measured signal-to-noise (S/N) % value of a sample indicates presence of specific Ab. Gray bar indicates the reactive response, whereas lower values specify seropositivity. Asterisks indicate the statistical differences between different time points on group level, calculated using one-way ANOVA, and followed by post-hoc Tukey’s test. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001. Error bars indicate standard error of the mean (SEM).
Fig. 6
Fig. 6. Humoral immune response to R65mono/H17N10 immunization and subsequent challenge infection in ferrets.
Serum samples were taken from all animals on d0, d10, d22, and 6 days post challenge (dpc6 = d28), and evaluated by a competitive Enzyme-linked Immunosorbent Assay (ELISA) specific for nucleoprotein (NP) (a, b) or hemagglutinin H5 binding antibodies (c, d). Reduction of the measured signal-to-noise (S/N) % value of a sample indicates presence of specific Ab. Gray bar indicates reactive response, whereas lower values specify seropositivity. Asterisks indicate the statistical differences between different time points on group level, calculated using one-way ANOVA, and followed by post-hoc Tukey´s test. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001. Error bars indicate standard error of the mean (SEM).
Fig. 7
Fig. 7. Experimental design.
Time frame and sampling regime used for the chicken (a) and the ferrets (b) vaccination study. Due to animal welfare no blood samples for serological evaluation were taken from chickens of juvenile group on d0.

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