Puzzling inefficiency of H5N1 influenza vaccines in Egyptian poultry

Kim, Jeong-Ki; Kayali, Ghazi; Walker, David; Forrest, H. S.; Ellebedy, Ali H.; Griffin, Yolanda; Rubrum, Adam; Bahgat, Mahmoud Mohamed; Kutkat, M. A.; Ali, Mohamed A.; Aldridge, Jerry R.; Negovetich, Nicholas J.; Krauss, Scott; Webby, Richard J.; Webster, Robert G.

doi:10.1073/pnas.1006419107

Cited by 93 publications

(80 citation statements)

References 43 publications

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“…Genetic drift accelerated, as can be clearly seen in Tables 2 and 5, and the number of amino acid substitutions increased each season, with a much higher rate observed in variant viruses [8]. The mutations at antigenic sites (S120N/D, R140G, S141P/L, I151T/V, K152E, N154D, A156T, R162K/I/E and A185E) can affect the immune response to vaccines [27]. One of the most important observations in the 2010/2011 season is that the classic group became widely distributed in the country, causing all human infections, and so became the predominant group.…”

Section: Hpai H5n1 Viruses Intomentioning

confidence: 89%

Evolution of highly pathogenic avian influenza H5N1 viruses in Egypt indicating progressive adaptation

Arafa¹,

Suarez

Kholosy³

et al. 2012

Arch Virol

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Highly pathogenic avian influenza (HPAI) virus of the H5N1 subtype was first diagnosed in poultry in Egypt in 2006, and since then the disease became enzootic in poultry throughout the country, affecting the poultry industry and village poultry as well as infecting humans. Vaccination has been used as a part of the control strategy to help to control the disease. Epidemiological data with sequence analysis of H5N1 viruses is important to link the mechanism of virus evolution in Egypt. This study describes the evolutionary pattern of Egyptian H5N1 viruses based on molecular characterization for the isolates collected from commercial poultry farms and village poultry from 2006 to 2011. Genetic analysis of the hemagglutinin (HA) gene was done by sequencing of the full-length H5 gene. The epidemiological pattern of disease outbreaks in Egyptian poultry farms seems to be seasonal with no specific geographic distribution across the country. The molecular epidemiological data revealed that there are two major groups of viruses: the classic group of subclade 2.2.1 and a variant group of 2.2.1.1. The classic group is prevailing mainly in village poultry and had fewer mutations compared to the originally introduced virus in 2006. Since 2009, this group has started to be transmitted back to commercial sectors. The variant group emerged by late 2007, was prevalent mainly in vaccinated commercial poultry, mutated continuously at a higher rate until 2010, and started to decline in 2011. Genetic analysis of the neuraminidase (NA) gene and the other six internal genes indicates a grouping of the Egyptian viruses similar to that obtained using the HA gene, with no obvious reassortments. The results of this study indicate that HPAI-H5N1 viruses are progressively evolving and adapting in Egypt and continue to acquire new mutations every season.

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Section: Hpai H5n1 Viruses Intomentioning

confidence: 89%

Evolution of highly pathogenic avian influenza H5N1 viruses in Egypt indicating progressive adaptation

Arafa¹,

Suarez

Kholosy³

et al. 2012

Arch Virol

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“…The decisions are solely based on the laboratory evaluation results (the approval threshold is >80% protection). Under laboratory conditions, all commercially available AI H5 vaccines in Egypt provided the required 80% protection level in seronegative Specific Pathogen Free (SPF) chickens against the Egyptian HPAI H5N1 isolates (Kim et al, 2010;unpublished data). Given the weak farm biosecurity and high disease burden in the Egyptian poultry sectors, regular evaluation of the effectiveness of vaccines under field conditions is essential.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the effectiveness of rHVT-H5, inactivated H5 and rHVT-H5 with inactivated H5 prime/boost vaccination regimes in commercial broiler chickens carrying MDAs against HPAI H5N1 clade 2.2.1 virus

Kilany¹,

Hassan²,

Safwat³

et al. 2015

Avian Pathology

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(2015) Comparison of the effectiveness of rHVT-H5, inactivated H5 and rHVT-H5 with inactivated H5 prime/boost vaccination regimes in commercial broiler chickens carrying MDAs against HPAI H5N1 clade 2.2.1 virus, Avian Pathology, 44:5, 333-341, DOI: 10.1080/03079457.2015 Vaccination is the main tool implemented in Egypt since 2007 to control H5N1 avian influenza. The present study aimed at comparing the effectiveness of three avian influenza vaccination regimes in commercial broiler chickens carrying high levels of maternally derived antibodies (MDAs). Day-old chicks were divided into four experimental groups. Group I received only the rHVT-H5 vaccine (recombinant turkey herpesvirus (HVT) which carries a H5 clade 2.2 insert) administered at D1. Group II received only the KV-H5 (an oil emulsion killed vaccine prepared from reassortant HPAI virus (A/duck/Anhui/1/06)) vaccine (inactivated reverse genetic H5N1 clade 2.3.4 virus) administered at D8. Group III received rHVT-H5 and KV-H5 as prime/boost. Group IV served as unvaccinated control. Weekly serological monitoring was conducted using the haemagglutination inhibition test. Two challenge experiments were conducted at D28 and D35 using HPAI H5N1 clade 2.2.1 virus. Birds were monitored daily 14 days post-challenge for morbidity and mortality, and oropharyngeal swabs were collected for virological monitoring. Initially, day-old chicks had high mean MDA titres (9 + 0.9 log 2 ). The MDA half-life was >7 and <7 days, respectively, for unvaccinated and vaccinated birds. Group III showed the highest post-vaccination humoral immune response and seroconversion rate. The highest protection rate against morbidity (80-90%) and mortality (90-90%) was obtained in Group III after challenge at D28 and D35, respectively, as compared to Group I (70-70%) and (80-90%) and Group II (0-0%) and (30-30%). Groups I and III had lower number of shedder birds. The vaccination regime with prime/boost conferred the highest and earliest protection, and can hence be recommended for the broiler production sector in endemic and high HPAI H5N1 challenge areas.

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“…The ability of RO-7 to decrease morbidity and mortality in virusinfected BALB/c mice, as well as reduce virus replication in the lung and pulmonary pathology, without inducing detectable antiviral resistance suggests it has potential for further development for clinical applications. (63). The reciprocal of the last serum dilution that inhibited hemagglutination was recorded as the HI titer.…”

Section: Discussionmentioning

confidence: 99%

The PA Endonuclease Inhibitor RO-7 Protects Mice from Lethal Challenge with Influenza A or B Viruses

Jones

Marathe

Vogel

et al. 2017

Antimicrob Agents Chemother

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Current influenza treatment relies on a single class of antiviral drugs, the neuraminidase inhibitors (NAIs), raising concern over the potential emergence of resistant variants and necessitating the development of novel drugs. In recent years, investigational inhibitors targeting the endonuclease activity of the influenza acidic polymerase (PA) protein have yielded encouraging results, although there are only limited data on their in vivo efficacy. Here, we examined the antiviral potential of the PA endonuclease inhibitor RO-7 in prophylactic and therapeutic regimens in BALB/c mice inoculated with influenza A/California/04/2009 (H1N1)pdm09 or B/Brisbane/60/2008 viruses, which represent currently circulating antigenic variants. RO-7 was administered to mice intraperitoneally twice daily at dosages of 6, 15, or 30 mg/ kg/day for 5 days, starting 4 h before or 24 or 48 h after virus inoculation, and showed no adverse effects. Prophylactic administration completely protected mice from lethal infection by influenza A or B virus. The level of therapeutic protection conferred depended upon the time of treatment initiation and RO-7 dosage, resulting in 60 to 100% and 80 to 100% survival with influenza A and B viruses, respectively. RO-7 treatment significantly decreased virus titers in the lung and lessened the extent and severity of lung damage. No PA endonuclease-inhibitor resistance was observed in viruses isolated from lungs of RO-7-treated mice, and the viruses remained susceptible to the drug at nanomolar concentrations in phenotypic assays. These in vivo efficacy results further highlight the potential of RO-7 for development as antiviral therapy for influenza A and B virus infections.

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Puzzling inefficiency of H5N1 influenza vaccines in Egyptian poultry

Cited by 93 publications

References 43 publications

Evolution of highly pathogenic avian influenza H5N1 viruses in Egypt indicating progressive adaptation

Evolution of highly pathogenic avian influenza H5N1 viruses in Egypt indicating progressive adaptation

Comparison of the effectiveness of rHVT-H5, inactivated H5 and rHVT-H5 with inactivated H5 prime/boost vaccination regimes in commercial broiler chickens carrying MDAs against HPAI H5N1 clade 2.2.1 virus

The PA Endonuclease Inhibitor RO-7 Protects Mice from Lethal Challenge with Influenza A or B Viruses

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