A novel hemagglutinin protein produced in bacteria protects chickens against H5N1 highly pathogenic avian influenza viruses by inducing H5 subtype-specific neutralizing antibodies
PBN-AR
Instytucja
Państwowy Instytut Weterynaryjny - Państwowy Instytut Badawczy
Informacje podstawowe
Główny język publikacji
en
Czasopismo
PLoS One (40pkt w roku publikacji)
ISSN
1932-6203
EISSN
1932-6203
Wydawca
PUBLIC LIBRARY SCIENCE 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
Rok publikacji
2017
Numer zeszytu
2
Strony od-do
e0172008, 1-21
Numer tomu
12
Identyfikator DOI
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Autorzy
Pozostali autorzy
+ 8
Słowa kluczowe
en
chickens
H5N1
antibodies
vaccines
birds
Enzyme-linked immunoassays
Vaccination and immunization
antigens
Open access
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Creative Commons — Uznanie autorstwa
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Razem z publikacją
Streszczenia
Język
en
Treść
The highly pathogenic (HP) H5N1 avian influenza viruses (AIVs) cause a mortality rate of up to 100% in infected chickens and pose a permanent pandemic threat. Attempts to obtain effective vaccines against H5N1 HPAIVs have focused on hemagglutinin (HA), an immunodominant viral antigen capable of eliciting neutralizing antibodies. The vast majority of vaccine projects have been performed using eukaryotic expression systems. In contrast, we used a bacterial expression system to produce vaccine HA protein (bacterial HA) according to our own design. The HA protein with the sequence of the H5N1 HPAIV strain was efficiently expressed in Escherichia coli, recovered in the form of inclusion bodies and refolded by dilution between two chromatographic purification steps. Antigenicity studies showed that the resulting antigen, referred to as rH5-E. coli, preserves conformational epitopes targeted by antibodies specific for H5-subtype HAs, inhibiting hemagglutination and/or neutralizing influenza viruses in vitro. The proper conformation of this protein and its ability to form functional oligomers were confirmed by a hemagglutination test. Consistent with the biochemical characteristics, prime-boost immunizations with adjuvanted rH5-E. coli protected 100% and 70% of specific pathogen-free, layer-type chickens against challenge with homologous and heterologous H5N1 HPAIVs, respectively. The observed protection was related to the positivity in the FluAC H5 test (IDVet) but not to hemagglutination-inhibiting antibody titers. Due to full protection, the effective contact transmission of the homologous challenge virus did not occur. Survivors from both challenges did not or only transiently shed the viruses, as established by viral RNA detection in oropharyngeal and cloacal swabs. Our results demonstrate that vaccination with rH5-E. coli could confer control of H5N1 HPAIV infection and transmission rates in chicken flocks, accompanied by reduced virus shedding. Moreover, the role of H5 subtype-specific neutralizing antibodies in anti-influenza immunity and a novel correlate of protection are indicated.
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praca doświadczalna
Inne
System-identifier
1259
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