Feasibility of reconstructed ancestral H5N1 influenza viruses for cross-clade protective vaccine development (original) (raw)
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Journal of virology, 2017
We have developed pandemic live attenuated influenza vaccines (pLAIV) against clade 1 H5N1 viruses on an Ann Arbor cold-adapted (ca) backbone that induced long-term immune memory. In 2015, many human infections caused by a new clade (2.2.1.1) of goose/Guangdong (gs/GD) lineage H5N1 viruses were reported in Egypt that prompted updating of the H5N1 pLAIV. We explored two strategies to generate suitable pLAIVs: first to modify the hemagglutinin gene of a highly pathogenic wild-type (wt) clade 2.2.1.1 virus A/Egypt/N03434/2009 (Egy/09) (H5N1) with its unmodified neuraminidase (NA) gene; this virus was designated Egy/09 ca The second approach was to select a low pathogenicity avian influenza H5 virus that elicited antibodies that cross-reacted with a broad range of H5 viruses, including the Egypt H5N1 viruses and contained a novel NA subtype for humans. We selected the low pathogenicity A/duck/Hokkaido/69/2000 (H5N3) virus (dk/Hok/00) for this purpose. Both candidate vaccines were attenu...
3 Biotech
The highly pathogenic avian H5N1 influenza viruses have been recognized as a potential pandemic threat to humans, and to the poultry industry since 1997. H5 viruses consist of a high mutation rate, so universal vaccine designing is very challenging. Here, we describe a vaccinomics approach to design a novel multi-epitope influenza vaccine, based on the highly conserved regions of surface glycoprotein, Hemagglutinin (HA). Initially, the HA protein sequences from Bangladeshi origin were retrieved and aligned by ClustalW. The sequences of 100% conserved regions extracted and analyzed to select the highest potential T-cell and B-cell epitope. The HTL and CTL analyses using IEDB tools showed that DVWTYNAELLVL-MEN possesses the highest affinity with MHC class I and II alleles, and it has the highest population coverage. The docking simulation study suggests that this epitope has the potential to interact with both MHC class I and MHC class II. The B-cell epitope prediction provides a potential peptide, GAIAGFIEGGWQGM. We further retrieved HA sequences of 3950 avian and 250 human H5 isolates from several populations of the world, where H5 was an epidemic. Surprisingly, these epitopes are more than 98% conserved in those regions which indicate their potentiality as a conserved vaccine. We have proposed a multi-epitope vaccine using these sequences and assess its stability and potentiality to induce B-cell immunity. In vivo study is necessary to corroborate this epitope as a vaccine, however, setting forth groundwork for wet-lab studies essential to mitigate pandemic threats and provide cross-protection of both avian and humans against H5 influenza viruses.
Vaccine, 2006
We generated a high-growth 7:1 reassortant (Len17/H5) that contained the hemagglutinin (HA) gene from non-pathogenic A/Duck/Potsdam/1402-6/86 (H5N2) virus and other genes from the cold-adapted (ca) attenuated A/Leningrad/134/17/57 (H2H2) strain. Len17/H5 demonstrated an attenuated phenotype in mice and did not infect chickens. Mice administered Len17/H5 either as a live-attenuated intranasal vaccine or as an inactivated intramuscular vaccine were substantially protected from lethal challenge with highly pathogenic A/Hong Kong/483/97 (H5N1) virus and were protected from pulmonary infection with antigenically distinct A/Hong Kong/213/2003 (H5N1) virus. The cross-protective effect correlated with the levels of virus-specific mucosal IgA and/or serum IgG antibodies. Our results suggest a new strategy of using classical genetic reassortment between a high-growth ca H2N2 strain and antigenically related non-pathogenic avian viruses to prepare live-attenuated and inactivated vaccines for influenza pandemic. Published by Elsevier Ltd.
Vaccines Developed for H5 Highly Pathogenic Avian Influenza in China
Annals of the New York Academy of Sciences, 2006
Since the first detection of highly pathogenic H5N1 avian influenza virus from sick goose in Guangdong province in China in 1996, scientists in China started to develop vaccines for avian influenza pandemic preparedness. An H5N2 inactivated vaccine was produced from a low pathogenic virus, A/turkey/England/N-28/73, and was used for the buffer zone vaccination in the H5N1 outbreaks in 2004 in China. We also generated a low pathogenic H5N1 reassortant virus A/Harbin/Re-1/2003 (Re-1) that derives its HA and NA genes from GSGD/96 virus and six internal genes from the high-growth A/Puerto Rico/8/34 (PR8) virus by using plasmid-based reverse genetics. The inactivated vaccine derived from Re-1 strain could induce more than 10 months protective immune response in chickens after one dose inoculation, and most importantly, this vaccine is immunogenic for geese and ducks. An H5N1 fowlpox vectored live vaccine was also generated by inserting the HA and NA genes of GSGD/96 virus in the genome of a fowlpox vaccine strain. Laboratory tests indicated that after one dose of immunization of this vaccine, chickens could develop an over than 40 weeks protective immune response against H5N1 virus challenge.
Vaccines, 2020
Vietnam is one of the countries most affected worldwide by the highly pathogenic avian influenza (HPAI) virus, which caused enormous economic loss and posed threats to public health. Over nearly two decades, with the antigenic changes in the diversified H5Ny viruses, the limited protective efficacy of the available vaccines was encountered. Therefore, it is necessary to approach a technology platform for the country to accelerate vaccine production that enables quick response to new influenza subtypes. This study utilized a powerful reverse genetics technique to successfully generate a recombinant H5N1 vaccine strain (designated as IBT-RG02) containing two surface proteins (haemagglutinin (HA) and neuraminidase (NA)) from the HPAI H5N1 (A/duck/Vietnam/HT2/2014(H5N1)) of the dominant clade 2.3.2.1c in Vietnam during 2012-2014. Importantly, the IBT-RG02 vaccine candidate has elicited high antibody titres in chickens (geometric mean titre (GMT) of 6.42 and 6.92, log2 on day 14 and day 28 p.i., respectively). To test the efficacy, immunized chickens were challenged with the circulating virulent strains. As results, there was a high protection rate of 91.6% chickens against the virulent A/DK/VN/Bacninh/NCVD-17A384/2017 of the same clade and a cross-protection of 83.3% against A/duck/TG/NAVET(3)/2013 virus of clade 1.1. Our promising results showed that we can independently master the reverse genetics technology for generation of highly immunogenic vaccine candidates, and henceforth, it is a timely manner to reformulate avian influenza virus vaccines against variable H5 clade HPAI viruses in Vietnam.