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1.
高致病性H5N1亚型禽流感病毒 (AIV) 严重威胁到人类健康,因此研制高效、安全的禽流感疫苗具有重要意义。以我国分离的首株人H5N1亚型禽流感病毒 (A/Anhui/1/2005) 作为研究对象,PCR扩增基质蛋白2 (M2) 和血凝素 (HA) 基因全长开放阅读框片段,构建共表达H5N1亚型AIV膜蛋白基因 M2和HA的重组质粒pStar-M2/HA。此外,还通过同源重组以293细胞包装出表达M2基因的重组腺病毒Ad-M2以及表达HA基因的重组腺病毒Ad-HA。用间接免疫荧光 (IFA) 方法检测到了各载体上插入基因的表达。按初免-加强程序分别用重组质粒pStar-M2/HA和重组腺病毒Ad-HA+Ad-M2免疫BALB/c小鼠,共免疫4次,每次间隔14 d。第1、3次用DNA疫苗,第2、4次用重组腺病毒载体疫苗,每次免疫前及末次免疫后14 d采集血清用于检测体液免疫应答,末次免疫后14 d采集脾淋巴细胞用于检测细胞免疫应答。血凝抑制 (HI) 实验检测到免疫后小鼠血清中的HI活性。ELISA实验检测到免疫后小鼠血清中抗H5N1亚型流感病毒表面蛋白的IgG抗体。ELISPOT实验检测到免疫后小鼠针对M2蛋白和HA蛋白的特异性细胞免疫应答。流感病毒M2与HA双基因共免疫的研究,为研究开发新型重组流感疫苗奠定了基础。 相似文献
2.
王利 《微生物学免疫学进展》2012,40(3):79-82
引起流感世界性大流行的主要原因与流感病毒表面抗原血凝素(HA)和神经氨酸酶(NA)频发的变异有很大关系,抗原的变异使得流感病毒可以逃逸机体的免疫防御,而且使许多应用中的疫苗失去防御效果。综述2009年世界暴发的H1N1新型流感病毒的结构在进化过程中发生的变异,有助于增加人们对流感病毒的了解,从而有效的治疗和预防流感大流行。 相似文献
3.
将我国分离的首株人H5N1亚型禽流感病毒A/Anhui/1/2005作为研究对象,扩增其HA和HA1基因片段并克隆至真核表达载体pStar,构建成真核表达质粒。通过Western blot和间接免疫荧光检测方法确认,构建的重组质粒在真核细胞中成功地表达了目的蛋白HA和HA1。将重组质粒免疫BALB/c小鼠,检测免疫后外周血中HA/HA1特异性抗体的效价,并比较HA和HA1的免疫原性。结果表明,重组质粒免疫后成功地诱导了体液免疫反应,且二者的血清抗体效价无显著性差异。 相似文献
4.
共表达H5N1流感病毒M1和HA基因的DNA疫苗与腺病毒载体疫苗的小鼠免疫评价 总被引:2,自引:0,他引:2
为评价在小鼠体内表达流感病毒M1和HA基因诱导的免疫反应,制备共表达H5N1亚型禽流感病毒 (A/Anhui/1/2005) 全长基质蛋白1 (M1) 基因和血凝素 (HA) 基因的重组DNA疫苗pStar-M1/HA和重组腺病毒载体疫苗Ad-M1/HA,将其按初免-加强程序免疫BALB/c小鼠,共免疫4次,每次间隔14 d。第1、3次用DNA疫苗,第2、4次用重组腺病毒载体疫苗,每次免疫前及末次免疫后14 d采集小鼠血清用于检测体液免疫应答,末次免疫后14 d采集小鼠脾淋巴细胞用于检测细胞免疫应答。血凝 相似文献
5.
目的探讨人、禽流感病毒在哺乳动物体内的遗传兼容性,为下一步研究H6亚型禽流感病毒重配和致病性变异的分子机制奠定基础。方法野鸭源A/H6N1亚型禽流感病毒A/Mallard/SanJiang/275/2007以101EID50~106EID50的攻毒剂量经鼻内途径感染小鼠,通过临床症状观察、病毒滴定和病理切片观察进行病毒学和组织学两方面检测对小鼠的致病性;同时,将此病毒与2009年A/H1N1流感病毒A/Changchun/01/2009(H1N1)混合感染豚鼠,分析两株病毒在哺乳动物体内的遗传兼容性。每天采集豚鼠鼻洗液并用噬斑纯化技术获得重配病毒,对获得的重配病毒进行全基因组序列的测定。结果 H6N1亚型禽流感病毒能直接感染小鼠,但对小鼠不致死。106EID50的攻毒剂量可有效感染小鼠,攻毒后第5天,小鼠表现出被毛较粗乱、活动减少、体重下降、呼吸急促的临床症状,但至攻毒后第10天开始康复,而对照组(MOCK)小鼠在14 d的观察期内无明显临床症状。病毒滴定结果表明,该病毒主要在小鼠肺脏和鼻甲骨中复制,病毒滴度可达104.5EID50/mL。病理学观察发现感染小鼠肺泡壁增厚,有大量炎性细胞浸润,纤维蛋白渗出并伴有轻微出血;在A/H6N1和A/H1N1混合感染豚鼠的重配实验中,经过三轮噬斑纯化从豚鼠鼻洗液中分离到6株重配病毒,说明A/H6N1亚型禽流感病毒与A/H1N1亚型流感病毒具有很好的遗传兼容性,能在豚鼠体内能发生重配。结论野鸭源A/H6N1亚型流感病毒无需适应就能够感染哺乳动物;该病毒与A/H1N1流感病毒具有很好的遗传兼容性,在哺乳动物体内能够发生基因重配,产生新的重配病毒,其公共卫生意义应引起高度关注。 相似文献
6.
建立新甲型H1N1流感病毒小鼠致死模型,为研究致病性、宿主适应性以及疫苗保护性提供动物模型,并寻找病毒在适应宿主过程中影响毒力和适应性的关键位点。将新甲型H1N1流感病毒A/四川/SWL1/2009 H1N1在小鼠中连续传15代,各代次毒株均在MDCK细胞上增殖后进行测序,根据序列分析结果选择6个传代毒株感染小鼠,连续监测14 d体重和死亡情况;并对第14代和15代病毒在噬斑实验纯化后克隆和测序分析。原代病毒不致死BABL/C小鼠,经动物体内连续传代适应宿主动物后,其毒力增强,具体表现为所选的6个传代毒株中第7、11、15代毒株可以100%致死试验小鼠;分析这6个传代毒株的全基因组表明这些毒株的部分氨基酸位点发生突变。新甲型H1N1流感病毒经小鼠体内连续传代后,建立了小鼠致死模型,病毒毒力增强可能与某些氨基酸位点的改变有关。 相似文献
7.
H1N1流感病毒属于常见的致病性病毒。流行病学调查研究表明,新生儿表型缺陷与流感病毒感染有关,但是具体机制还不明确。为了探讨H1N1流感病毒对胚胎发育的影响,本文通过流感病毒感染孕母鼠来构建流感病毒宫内感染的动物模型,分别在胚胎发育至E14.5、E15.5、E16.5、E17.5、E18.5 d以及出生1 d后测量各胚胎的体长,并在体视镜下观察胚胎体表各血管和器官来分析胚胎外表发育的情况,然后采用阿尔新蓝-茜素红染色法观察各发育时期胚胎骨骼发育的情况。结果表明,流感病毒感染的小鼠胚胎的体长明显降低。外部器官发育的差异性可体现在眼、耳等器官,攻毒组成型稍晚,尾部异常卷曲更为严重。各骨骼发育攻毒组较对照组更迟缓,但没有出现长短肢或骨骼缺失等严重异常表型。本研究首次构建了流感病毒宫内感染的动物模型,探究了H1N1流感病毒对小鼠胚胎表型发育的影响。 相似文献
8.
【目的】揭示一例混合感染中H3N2和N7N9流感病毒的分子遗传特性。【方法】通过荧光定量PCR法对标本进行流感病毒分型检测。通过二代测序技术对病毒分离物进行全基因组测序分析。【结果】2013年4月在南京市检测到一例人季节性H3N2流感病毒和禽流感H7N9病毒混合感染,混合病毒分别命名为A/Nanjing/M1/2013 (H3N2) (M1-H3N2)和A/Nanjing/M2/2013 (H7N9) (M2-H7N9)。分离株M2-H7N9 HA蛋白的Q226L位点和PB2蛋白E627K位点发生突变,增强了病毒对人体的感染能力。【结论】报道了一起人混合感染H3N2和N7N9流感病毒病例,提示人可能成为流感病毒基因“混合器”,应高度关注H7N9病毒与人季节性流感病毒的基因重配现象。 相似文献
9.
本研究通过对深圳市4名甲流重症患者的血清抗体及其所感染的新甲型H1N1流感病毒的抗原性和分子特点的分析,发现这些患者在感染后短期内产生的血清中和抗体滴度均不超过1:20,不能起到有效的保护作用;交叉血凝抑制实验的结果显示新H1N1病毒与季节性H1N1和H3N2流感病毒无任何交叉反应,抗原性差异很大,而患者所感染的病毒与标准株的抗原性则没有太大差异;分子特点的分析表明新H1N1病毒进入人群后依然属于经典的猪流感亚系,4名重症患者感染的病毒不具备高致病性流感病毒的遗传特点,几个氨基酸位点的变异没有影响病毒的毒力和致病性,只有一株毒株的NA蛋白发生了His275Tyr的突变,产生了对达菲等神经氨酸酶抑制剂的耐药性。 相似文献
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E. Frobert M. Bouscambert-Duchamp V. Escuret S. Mundweiler M. Barthélémy F. Morfin M. Valette C. Gerdil B. Lina O. Ferraris 《Current microbiology》2010,61(1):25-28
The A(H5N1) influenza virus pandemic may be the result of avian H5N1 adapting to humans, leading to massive human to human
transmission in a context of a lack of pre-existing immunity. As A(H1N1) and A(H5N1) share the same neuraminidase subtype,
anti-N1 antibodies subsequent to H1N1 infections or vaccinations may confer some protection against A(H5N1). We analysed,
by microneutralization assay, the A/Vietnam/1194/04 (H5N1) anti-N1 cross-protection acquired either during A/NewCaledonia/20/99
(H1N1) infection or vaccination. In cases with documented H1N1 infection, H5N1 cross-protection could be observed only in
patients born between 1930 and 1950. No such protection was detected in the sera of vaccinated individuals. 相似文献
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HuaLan Chen 《中国科学:生命科学英文版》2009,52(5):419-427
H5N1 highly pathogenic avian influenza virus was first detected in a goose in Guangdong Province of China in 1996. Multiple
genotypes of H5N1 viruses have been identified from apparently healthy waterfowl since 1999. In the years 2004–2008, over
100 outbreaks in domestic poultry occurred in 23 provinces and caused severe economic damage to the poultry industry in China.
Beginning from 2004, a culling plus vaccination strategy has been implemented for the control of epidemics. Since then, over
35420000 poultry have been depopulated, and over 55 billion doses of the different vaccines have been used to control the
outbreaks. Although it is logistically impossible to vaccinate every single bird in China due to the large poultry population
and the complicated rearing styles, there is no doubt that the increased vaccination coverage has resulted in decreased disease
epidemic and environmental virus loading. The experience in China suggests that vaccination has played an important role in
the protection of poultry from H5N1 virus infection, the reduction of virus load in the environment, and the prevention of
H5N1 virus transmission from poultry to humans.
Supported by the Key Animal Infectious Disease Control Program of the Ministry of Agriculture, the Chinese National S&T Plan(Grant
No. 2004BA519A-57), National Key Basic Research and Development Program of China (Grant Nos: 2005CB523005, 2005CB523200). 相似文献
15.
The evolutionary dynamics of the H5N1 virus present a challenge for conventional control
measures. Efforts must consider the regional aspects of endemic H5N1.The H5N1 virus has spread across Asia, Europe and Africa, and has infected birds in several
endemic areas, including China, Indonesia, Vietnam and Egypt. H5N1 outbreaks pose a massive
threat for the poultry industry and, ultimately, for human health [1]. However, the rapid spread of the virus also offers the opportunity to
study and learn from its dynamics in the wild. The insights gained should inform new public
health policies and preventive actions against a possible pandemic.Progress in influenza research has been impressive. In particular, the application of reverse
genetics has led to the identification of mutations and reassortment changes that determine
virus virulence. Perhaps the most significant results come from the two now infamous studies,
published in Nature and Science, about the generation of recombinant H5N1
viruses that are transmissible in ferrets [2,3]. These advances show that we are steadily elucidating influenza
virus at the molecular level. By contrast, our understanding of the dynamics of highly
pathogenic influenza virus in the environment remains limited [4,5].Highly pathogenic avian influenza (HPAI) is an important poultry disease. The major reservoir
of the virus is wild waterfowl, and infected birds are usually asymptomatic as a result of
long-term evolutionary adaptation [1,6]. After transmission from wild waterfowl to poultry, however, avian
influenza viruses occasionally become highly pathogenic and can cause mortalities of up to
100% within 48 h of infection. The standard method for controlling an HPAI outbreak is the
testing and culling of all infected poultry, and the setting up of a concentric control area
around the infected flock.The HPAI H5N1 virus, circulating in Eurasia and Africa, emerged in China around 1997
[1] but it only infected terrestrial birds at the
time. Continuous transmission in poultry eventually allowed the virus to evolve, resulting in
large outbreaks in China in 2005 with high mortality in wild waterfowl. The virus spread
rapidly, probably though migratory birds, to Central Asia, Europe, the Middle East and Africa.
Such ‘east to west'' movements of H5N1 viruses over comparably long distances have
not since been recorded. Moreover, migrating wildfowl have begun to spread the virus
intermittently between Asia and Siberia [7]. This H5N1
lineage is the longest-circulating HPAI virus that has been reported, and it has reached
epizootic levels in both domestic and wild bird populations.…the challenge is to understand the evolution of H5N1 to better
predict new strains that could become a serious threat for human healthOne of the striking characteristics of the H5N1 lineage, in contrast with other HPAI, is its
infectivity toward mammals. H5N1 can be directly transmitted from birds to humans and cause
severe disease, although it has a significantly lower transmissibility than seasonal influenza
viruses [1]. So far, 608 cases of human H5N1 infections
have been reported with 59% mortality [5]. Most human
infections have resulted from close contact with H5N1-infected poultry or poultry products,
and no sustained human–human transmission has as yet been documented. Nonetheless, a
potential H5N1 pandemic remains a great concern for public health.The viruses that caused the five influenza pandemics since 1900 arose by two mechanisms:
reassortment among avian, human and swine influenza viruses, and accumulation of mutations in
an avian influenza virus [1,8]. Triple reassortment between avian H5N1, swine H3N1 and H1N1 viruses, and
double reassortment between avian H5N1 and H9N2 viruses has already been reported in Asia,
which raises concerns about new reassortment viruses that could infect humans [9,10]. Meanwhile, research has
identified some 80 genetic mutations that could increase infectivity of avian influenza
viruses in mammals, and thus potentially facilitate avian influenza evolution to generate a
pandemic strain [8,11].
H5N1 strains with some of these mutations have often been found in bird populations
[5] and in human H5N1 strains [12]. Indeed, specific mutations that could confer switching in
receptor-binding specificity were reported in H5N1-infected patients in Thailand
[13]. The two controversial studies published in
Nature and Science also showed how a handful of mutations might enable the
H5N1 virus to be transmitted between humans [2,3]. Pathogenic variants of the H5N1 virus with a higher pandemic
potential could naturally evolve; the challenge is to understand the evolution of H5N1 to
better predict new strains that could become a serious threat for human health.…continuous replication of H5N1 virus in Egypt has provided a
valuable opportunity to study the impact of genetic evolution on phenotypic variation
without reassortmentThe evolutionary dynamics of the Egyptian H5N1 strains provide clues to understanding the
pandemic potential of H5N1. The virus was introduced only once in Egypt, in early 2006, and
spread among a variety of bird species, including chickens, ducks, turkeys, geese and quail
[14]. The virus rapidly evolved to form a
phylogenetically distinct clade that has since diverged into multiple sublineages
[15]. Thus, continuous replication of H5N1 virus in
Egypt has provided a valuable opportunity to study the impact of genetic evolution on
phenotypic variation without reassortment.After diversification in local bird populations, some new H5 sublineages have emerged in
Egypt with a higher affinity for human-type receptors. Indeed, since their emergence in 2008,
almost all human H5N1 strains in Egypt have been phylogenetically grouped into these new
sublineages, which can be transmitted to humans with a higher efficacy than other avian
influenza viruses. This might explain why, since 2009, Egypt has had the highest number of
human cases of H5N1 infection, with more than 50% of the cases worldwide [5]. Fortunately, these Egyptian H5N1 sublineages still do not have
binding affinity for receptors in the upper respiratory tract and, therefore, do not sustain
transmission in humans. However, it increases the risk of H5N1 variants that are better
adapted to humans after viral replication in infected patients.…Egypt is regarded as the country with the highest H5N1 pandemic
potential worldwideThe Egyptian H5N1 sublineages are also diversifying antigenically in the field, as some are
no longer crossreactive to other co-circulating sublineages [15]. Moreover, faint traces of species-specific evolutionary changes have
been detected [16], implying a change in their host
species. It shows that the H5N1 virus has undergone significant diversification in Egypt
during the past seven years. Of greater concern, however, are Egyptian H5N1 strains that carry
mammalian influenza virus type PB2 and have lost the N-linked 158 glycosylation site in the
top region of haemagglutinin [15,17], both of which can potentially facilitate viral transmission to humans.
The genetic diversification of H5N1 virus in Egypt represents an increasing pandemic
potential, and Egypt is regarded as the country with the highest H5N1 pandemic potential
worldwide [18].A similar situation exists in other geographical areas. Multiple clades and sublineages of
H5N1 are co-circulating in Asia, occasionally enabling reassortment events within and beyond
the viral subtypes in the field [19,20]. Several H5N1 strains with enhanced binding affinity to human-type
receptors have been reported in Indonesia [12].
Similarly, avian and swine H5N1 strains with an altered receptor-binding preference have been
isolated sporadically in Indonesia and Laos [21,22]. As in other areas, distinct groups of H5N1 viruses are
circulating amongst themselves and with other avian influenza viruses, generating diverse
viral phenotypes in nature. The evolutionary dynamics of H5N1 might even accelerate in the
wild. H5N1 viruses diverge genetically in ducks [23];
they can transfer the virus over long distances by migration. Thus, the H5N1 virus has
established a complex life cycle in nature with accelerated evolutionary dynamics. The
pandemic threat of H5N1 remains a serious concern and might be increasing.Control measures based on isolating and culling are still the gold standard for controlling
the early phase of an H5N1 outbreak, and worked against the H5N1 outbreaks in Hong Kong in
1997 and in Thailand in 2004 [4]. However, this measure
failed in several countries and made H5N1 endemic. Cross-border circulation of H5N1 further
complicates implementation of a classical control strategy based on culling in the infected
area.In response, public health officials in several countries, including Egypt and Indonesia,
advocate poultry vaccination as a preventive or adjunct control measure [1]. Although vaccination does not completely prevent infections, its
proper use can help to control avian influenza outbreaks by reducing virus transmission from
infected animals. However, it can also increase vaccine-driven evolution among avian influenza
viruses. The endemic status of H5N1, which can cause devastating local epidemics, puts
pressure on health officers to use a vaccine or a vaccination strategy that might eventually
increase selective pressure and thereby accelerate H5N1 evolution. Given the high mutability
and diversity of circulating viruses, it seems best to avoid using a vaccine based on a strain
from a different geographical area because there would only be a partial antigen match; such a
heterologous vaccine would only be effective in the short term compared with a homologous
vaccine. During past control of H5N1 epidemics using imported vaccines, escape mutants have
emerged within about a year of the start of vaccination, which made the epidemic even worse
[14]. When a vaccination strategy is implemented in
an endemic area, the vaccine seed strain should be selected from the same geographical area to
try to get the longest possible protection. Vaccine seed virus selection must be periodically
revised to produce well-matched and efficacious vaccines.Close communication and workshops hold the greatest potential for
controlling the H5N1 virusIn most cases, H5 vaccine for an endemic area comes from a foreign supplier. It would be
necessary to enable foreign manufacturers to produce customized H5 vaccines based on epidemic
strains from different areas. The best approach might be a plasmid-based reverse genetics
system to construct vaccine seed viruses [1]. In
egg-based production, which is the basis of flu vaccine production, the seed virus needs to be
adapted for high growth. This time-consuming step carries the risk of antigenic changes during
vaccine production. Yet, advances in influenza reverse genetics have led to the development of
cell culture systems to produce recombinant viruses, which would enable rapid genetic
mutagenesis and reassortment. Once reverse genetics generates a virus genome that is well
adapted to growth in cell culture, the haemagglutinin and neuraminidase genes can be easily
interchanged with those of other influenza viruses. In addition, virus growth in cell culture
can shorten production time, which increases the probability of selecting a seed virus
antigenically appropriate for the upcoming flu season, and enables a rapid increase in
production if necessary [24].A control strategy imposed without consideration of regional customs will
not be successfulGiven the zoonotic risks of influenza viruses to both humans and animals, the establishment
of a vaccine production system applicable to both human and animal infections is an urgent
issue. The capacity of vaccine production needs to be flexible for seasonal, pre-pandemic and
pandemic vaccines. Advances in genetic engineering facilitate in vitro control of
human- and avian-type receptor expression on cultured cells, which should allow both human and
avian influenza viruses to grow in the same system. As vaccine production capacity based on
cell culture develops, commercial production of H5N1 vaccines tailored to each geographical
area should become possible. In addition, emergency vaccination guidelines, such as
pre-pandemic vaccine stockpiling, expanding and accelerating vaccine production and setting
vaccination priorities, should be formulated in a business–government partnership, to
ensure pandemic preparation. There is no guarantee that the H5N1 virus will be the next
pandemic influenza strain. However, exploring options for versatile vaccine manufacturing is a
key to controlling zoonotic influenza viruses, including H5N1.The complexity of H5N1 ecology also makes control of endemic H5N1 by vaccination a complex
task. The problem is that antigenically different groups of viruses, which are not
crossreactive, are often co-circulating in endemic areas. Circulation of viruses in each
sublineage is not restricted in terms of geography or host species, which complicates efforts
to use a vaccine produced against antigens from a single virus strain [15]. Of greater concern, H5N1 virus infects a variety of bird species
[1], which means the vaccination targets have
expanded. Bird species differ in their optimal vaccination protocol—for example, the
single vaccination used routinely in chickens does not induce an adequate immune response in
turkeys, which require multi-dose vaccination at an older age [25]. Furthermore, rearing many bird species and their hybrid breeds in
uncontrolled confinement is common in H5N1 endemic countries, especially in rural areas.
Therefore, the immunogenicity of existing vaccines is probably inadequate to protect all
target species with a single vaccination scheme. Endemic H5N1 already forces public health
officials to redefine vaccine development policy to improve both vaccine immunogenicity and
vaccination regime.Unfortunately, it is unlikely that science will ever produce a clear
answer as to when, where and how the next pandemic influenza virus will emergeToday, there are numerous techniques that could overcome these problems by increasing
immunogenic potency and crossreactivity. Innovative vaccine formats—multivalent,
universal, nasal and synthetic vaccines—possibly coupled with the use of adjuvants,
could improve the global vaccine supply [24]. These new
technologies should be applied as soon as possible. Nevertheless, no single technique can
probably resolve the underlying complexity of H5N1 dynamics. Over-reliance on vaccination
might therefore only worsen the situation. Vaccination can help control endemic H5N1 only when
administered as part of an integrated control programme that includes surveillance, culling,
restricting host movement and enhanced quarantine and biosecurity.The complex evolutionary dynamics of the H5N1 virus are challenging host species barriers and
the ecology brings H5N1 into close proximity to humans [1]. The close link between the virus and humans is a multifaceted phenomenon
that can affect health in myriad ways. Thus, we need to redefine control strategies to address
the nature of H5N1 dynamics. Surveillance is the basis of infection control in the field. Wild
birds and their predators should be included as surveillance targets, thereby expanding the
H5N1 host species range. Another drawback is the fact that epidemiological studies focus
mainly on virus genotyping. Although genetic data is informative, the diversity of H5N1
viruses makes characterization based only on genetic traits difficult. Characterization of
viral phenotypes—antigenicity, receptor-binding preference, pathogenicity and
transmissibility—is equally important for investigating the evolutionary dynamics of
H5N1 viruses in nature. We would need techniques to determine easily viral phenotype, in
particular new rapid diagnostic systems that can be used for timely epidemiological
investigations and rapid infection control measures [1].
For example, portable kits that can determine virus receptor specificity would allow field
testing of whether a particular avian influenza virus strain has adapted to human-type
receptors, thereby adding a new dimension for characterizing and assessing H5N1
outbreaks.Our perception of H5N1 control should change from short-term hunting to
long-term controlThe large-scale slaughter of all known and suspected infected birds in H5N1 endemic countries
is hugely expensive in terms of execution costs and compensation for lost poultry. Financial
assistance from international organizations might be needed to promote the thorough
implementation of such a policy. However, H5N1 endemic countries are not all poor nations and
some have already built a certain level of technology infrastructure. Thus, transfer of
epidemiological skills and concepts to local health officers and scientists is a priority.
Overseas collaborations between technologically developed countries and their institutions,
and H5N1 endemic countries and their institutions, should be established at a functional
level. Close communication and workshops hold the greatest potential for controlling the H5N1
virus. Such projects supported by governments and funding agencies would encourage
establishment of bilateral and multilateral relationships between developed countries and the
developing countries, which are the epicentres of H5N1 outbreaks. Sharing information about
risk and risk management is one of the key methods for reducing the threat of future H5N1
epidemics.Globalization has had major benefits for international travel and trade, and sharing of
information. The improvements in information technology have dramatically increased the speed
and ease of data flow [26]. Intelligence networks
facilitate instantaneous sharing of information and enable global warnings about potential
hazards as well as problem-solving. Moreover, collaborative research centres, which have been
established on reciprocal bases between scientifically advanced countries and institutes and
overseas partner countries and institutes in Asia, Africa and Latin America, are important
players in information networking—for instance the Institute Pasteur Network, the
Mahidol Oxford Tropical Medicine Research Unit and Japan Initiative for Global Research
Network on Infectious Diseases. Linking such laboratory-based networks should be the next
step. This would have a profound synergistic effect by maximizing research capacity, human
resources and geographic coverage to build a robust global-scale network for infection
control.However, regional socio-cultural issues can be a significant concern for virus control
wherever accepted values and scientific understanding might differ. Multiple local and
regional factors—customs, religion, politics and economics—can affect H5N1 control
in an area. Successful implementation of an H5N1 control strategy depends largely on mutual
understanding and consideration of local idiosyncrasies.Some examples from Egypt show how regional identity can be closely linked with local public
health initiatives. Egypt is an Islamic nation and bird meat is an important source of animal
protein, and the only source in some rural areas [14].
A large proportion of Egyptian households in rural areas raise poultry. Although broiler and
layer chickens are raised under modern hygienic controls on commercial farms, backyard birds
are raised in open uncontrolled farms, leaving them free to interact with other birds (Fig 1A). The poultry meat trade depends mainly on live bird markets in
traditional bazaars (Fig 1B), because of a preference for freshly
slaughtered poultry. Pigeon towers are built on farms, backyards and roofs throughout villages
to raise pigeons for eating. Generally, birds in Egypt are raised in proximity to humans
(Fig 1C), which presents an increasing risk of human H5N1 infection in
Egypt and establishment of endemic H5N1 in birds nationwide.Open in a separate windowFigure 1Socio-cultural traditions in rearing birds for food in Egypt. (A) Free rearing
of backyard birds. (B) Live birds at a downtown market. (C) An example of
the intertwined relationship between birds and humans.Such regional identity is inseparable from socio-cultural contexts, making fundamental change
virtually impossible. Although there are many scenarios in which a local public health system
could be improved by food safety standards and veterinary inspection or short-term closing of
live bird markets for virus clearance, H5N1 control measures have to be implemented whilst
respecting the intrinsic socio-cultural traditions in the region. A control strategy imposed
without consideration of regional customs will not be successful. It is the local health
officers and scientists who are best suited to address the enormous complexity and breadth of
issues required for H5N1 control. They also experience H5N1 outbreaks in their area on a
regular basis and have a great incentive to be involved in infection control. Therefore, it is
important to include local expertise in planning and implementing a control
strategy.Science in an area such as infectious disease research can no longer be
viewed as independent of societal needs…Science is frequently looked at as if it can produce a ‘silver bullet'' to solve
every problem. Early success in vaccine and antibiotic development also created a false sense
of optimism that scientific methods could eliminate the risk of infection. However, the
reality has turned out to be different—some infectious diseases remain uncontrollable
and far from eradication. Given the mutable and diversifying nature of avian influenza
viruses, there is a significant possibility that different avian influenza subtypes and
strains do not follow a single evolutionary pathway. Unfortunately, it is unlikely that
science will ever produce a clear answer as to when, where and how the next pandemic influenza
virus will emerge. Our perception of H5N1 control should change from short-term hunting to
long-term control. The ecology of H5N1 virus brings it into close proximity to humans. The
most important strategy is to minimize contact between terrestrial poultry and wild waterfowl
to segregate H5N1 in poultry, because H5N1 spread would be uncontrollable if it established a
stable equilibrium in waterfowl. For example, H5N1 viruses in Siberia have not been
consistently isolated each year from carcasses and faeces of wildfowl migrating from Asia
[7]. This implies that H5N1 circulation in the wild
still largely depends on occasional introduction from poultry. It is possible that trials to
limit H5N1 infection in poultry would lead to a reduction in viral spread and a dwindling
evolutionary path in nature. Infection control policy must abandon fixed strategies in favour
of flexible ones to keep pace with the evolutionary dynamics of pathogens such as H5N1 (Fig 2).Open in a separate windowFigure 2Changing dynamics of H5N1 virus in the field. Endemic H5N1 virus diversifies in nature,
making traditional control measures extremely difficult.Today''s infection control strategy is becoming largely dependent on the reliability and
accuracy of information networking. However, the vast flood of scientific information can hide
erroneous information and easily mislead the public [26]. Of greater concern, globalization has prompted the centralization of
capital and resources, which can lead to an overemphasis on certain research topics. As a
consequence, research projects are often short term, without consideration of effects that
might have a long-term social impact [27]. This has led
to a debate about whether to limit publication of certain types of research or keep scientific
information completely accessible. There is probably no easy answer to this. Our global
society needs a more mature approach to support research projects that are accurate
reflections of societal needs in public health. At the same time, the increasing links between
science and society put more pressure on science to play a greater role in society. This is a
serious dilemma—how to use science to solve societal problems whilst maintaining its
autonomy [27]. Science in an area such as infectious
disease research can no longer be viewed as independent of societal needs; we need to
establish a balance between the pursuit of independent basic research and its application for
solving clinical problems and crises.?
Open in a separate windowYohei WatanabeOpen in a separate windowKazuyoshi IkutaOpen in a separate windowMadiha S Ibrahim 相似文献
16.
17.
Previously we demonstrated the versatile utility of the Parapoxvirus Orf virus (ORFV) as a vector platform for the development of potent recombinant vaccines. In this study we present the generation of new ORFV recombinants expressing the hemagglutinin (HA) or nucleoprotein (NP) of the highly pathogenic avian influenza virus (HPAIV) H5N1. Correct foreign gene expression was examined in vitro by immunofluorescence, Western blotting and flow cytometry. The protective potential of both recombinants was evaluated in the mouse challenge model. Despite adequate expression of NP, the recombinant D1701-V-NPh5 completely failed to protect mice from lethal challenge. However, the H5 HA-expressing recombinant D1701-V-HAh5n mediated solid protection in a dose-dependent manner. Two intramuscular (i.m.) injections of the HA-expressing recombinant protected all animals from lethal HPAIV infection without loss of body weight. Notably, the immunized mice resisted cross-clade H5N1 and heterologous H1N1 (strain PR8) influenza virus challenge. In vivo antibody-mediated depletion of CD4-positive and/or CD8-posititve T-cell subpopulations during immunization and/or challenge infection implicated the relevance of CD4-positive T-cells for induction of protective immunity by D1701-V-HAh5n, whereas the absence of CD8-positive T-cells did not significantly influence protection. In summary, this study validates the potential of the ORFV vectored vaccines also to combat HPAIV. 相似文献
18.
Charles Nfon Yohannes Berhane John Pasick Carissa Embury-Hyatt Gary Kobinger Darwyn Kobasa Shawn Babiuk 《PloS one》2012,7(12)
There is a critical need to have vaccines that can protect against emerging pandemic influenza viruses. Commonly used influenza vaccines are killed whole virus that protect against homologous and not heterologous virus. Using chickens we have explored the possibility of using live low pathogenic avian influenza (LPAI) A/goose/AB/223/2005 H1N1 or A/WBS/MB/325/2006 H1N2 to induce immunity against heterologous highly pathogenic avian influenza (HPAI) A/chicken/Vietnam/14/2005 H5N1. H1N1 and H1N2 replicated in chickens but did not cause clinical disease. Following infection, chickens developed nucleoprotein and H1 specific antibodies, and reduced H5N1 plaque size in vitro in the absence of H5 neutralizing antibodies at 21 days post infection (DPI). In addition, heterologous cell mediated immunity (CMI) was demonstrated by antigen-specific proliferation and IFN-γ secretion in PBMCs re-stimulated with H5N1 antigen. Following H5N1 challenge of both pre-infected and naïve controls chickens housed together, all naïve chickens developed acute disease and died while H1N1 or H1N2 pre-infected chickens had reduced clinical disease and 70–80% survived. H1N1 or H1N2 pre-infected chickens were also challenged with H5N1 and naïve chickens placed in the same room one day later. All pre-infected birds were protected from H5N1 challenge but shed infectious virus to naïve contact chickens. However, disease onset, severity and mortality was reduced and delayed in the naïve contacts compared to directly inoculated naïve controls. These results indicate that prior infection with LPAI virus can generate heterologous protection against HPAI H5N1 in the absence of specific H5 antibody. 相似文献
19.
糖尿病患者免疫功能低下,是流感病毒感染的高危人群.研制有效的流感病毒疫苗对糖尿病患者尤为重要.以注射STZ的方法建立糖尿病小鼠模型,比较糖尿病小鼠和健康小鼠对H5N1病毒易感性的差异.病毒感染3 d后糖尿病小鼠的肺部病毒滴度比健康小鼠高,显示糖尿病小鼠对H5N1病毒更易感.用一次免疫的方法接种不同剂量的H5N1灭活疫苗(单独免疫或与佐剂共同免疫),比较其在糖尿病小鼠和健康小鼠诱导抗体应答的能力.一次免疫H5N1流感病毒灭活疫苗可诱导糖尿病小鼠产生体液免疫应答,但其抗体量低于健康小鼠,增加疫苗剂量可提高抗体水平.佐剂能增强H5N1全病毒灭活疫苗在糖尿病小鼠体内诱导的抗体反应. 相似文献
20.
Casey PG 《Bioengineered bugs》2012,3(3):144
The recent moratorium on research using engineered H5N1 influenza viruses is a move which cannot achieve its aims as it ignores the prevalence of molecular biology. 相似文献