Influenza A virus H5N1

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Influenza A virus H5N1
Colorized transmission electron micrograph of Avian influenza A H5N1 viruses.jpg

Electron microscope image of H5N1
(virus is digitally colored gold)

Systematics
Classification : Viruses
Area : Riboviria
Empire : Orthornavirae
Phylum : Negarnaviricota
Subphylum : Polyploviricotina
Class : Insthoviricetes
Order : Articulavirales
Family : Orthomyxoviridae
Genre : Alpha influenza virus
Type : Influenza A Virus
Subspecies : H5N1
Taxonomic characteristics
Genome : (-) ssRNA segmented
Baltimore : Group 5
Symmetry : helical
Cover : available
Scientific name
Influenza A virus A / H5N1
Short name
FLUAV / (H5N1)
Left
NCBI  Taxonomy: 102793
ViralZone ( ExPASy , SIB): 130
ICTV Taxon History: 201853956

Influenza A virus H5N1 (A / H5N1) denotes a subtype of the influenza A virus (genus alphainfluenza virus ) from the orthomyxovirus family. This virus is the causative agent of a common language as avian influenza designated viral disease . Some variants of the pathogen to the highly pathogenic ( "originating from birds") avian influenza - viruses detected (HPAI). These variants include, in particular, the so-called Asia type ,which initially appeared in China, which is considered particularly virulent and has also passed on to humans several times ( → number of cases ). The virus has been known in the initially less pathogenic form since 1959, and all highly pathogenic H5N1 variants that have spread worldwide since 1997 have a common "ancestor" in the virus sample A / Goose / Guangdong / 1/96 secured in 1996.

For information about other influenza viruses that are also spread among poultry, see Avian influenza and the list of subtypes of the influenza A virus .

Special features

As with all other influenza viruses, the eight genome segments of this subtype encode ten or eleven viral proteins : hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), the matrix proteins ( M1 ) and ( M2 ), the polymerase proteins (PB1) , (PB2) and (PA), the non-structural proteins ( NS1 ) and ( NS2 ) and occasionally also PB1-F2. Three of the eight gene segments (M, NS and PB1) code for two proteins each by alternative splicing . The NS segment contains the NS gene from which the two non-structural proteins (NS1) and (NS2) are formed, while the matrix proteins 1 and 2 are formed from the M segment and PB1 and PB1-F2 from the PB1 segment.

Influenza A / H5N1 virion

Various mutations in genes of the influenza virus H5N1 have been described with regard to the increased pathogenicity compared to other influenza viruses . Influenza viruses of serotype H5N1 can according to their pathogenicity in low pathogenic avian influenza viruses (Engl. Low-pathogenic avian influenza , LPAI) and highly pathogenic avian influenza viruses (Engl. Highly pathogenic avian influenza , HPAI) are divided. A characteristic feature of HPAI is the multibasic interface (engl. Multi-basic cleavage site ) in the haemagglutinin, a proteolytic activation of the fusion domain, and thus the penetration of the host cell facilitated. When infected, some H5N1 subtypes lead to an excessive activation of the innate immune response by hemagglutinin (HA5), single-stranded and double-stranded viral RNA , which manifests itself in an increased release of cytokines by immune cells and has been referred to as a cytokine storm . The I227S mutation in hemagglutinin has been associated with increased pathogenicity in mice. Changing glycosylations in hemagglutinin can facilitate replication. A mutation in neuraminidase (H274Y) observed in some H5N1 viruses leads to resistance to oseltamivir . Some variants of PB1-F2 (mutant N66S) lead to increased apoptosis in infected cells. At one end of the NS gene there is a section that presumably plays a role in determining the severity of the course of the infection. Changes in this gene segment lead to a variation in a variable area on the NS1 protein. In the case of A / H5N1, this variable protein area has a structure that, particularly in humans, binds very effectively to so-called PDZ domains (special sub-area of ​​protein molecules in cells) and thereby disrupts the signal transmission in the cells particularly strongly. Such a disruption of the signal transmission then causes an overstimulation of the immune system , in which many inflammatory messengers are released.

In a study that was published in the journal Nature in mid-March 2006 , researchers argued that, unlike human influenza viruses, A / H5N1 binds to receptors that are mainly located in the alveoli of humans and animals , but hardly in the alveoli upper respiratory tract. This is the reason that human-to-human transmission has so far occurred very rarely, since in the case of a so-called droplet infection, mainly substances from the throat and pharynx are spread via the breath. At the same time, the increase in the lower lung area is partly responsible for the more severe course of the disease and the increased mortality in humans. Furthermore, mutations have been described that occur more frequently in humans or in birds and facilitate replication in the respective host .

Environmental stability

Depending on the temperature, the environmental stability ( tenacity ) of the influenza viruses and thus also of the subtype A / H5N1 with all its other variants is relatively low compared to other viruses. At a normal summer daytime temperature of around 20 ° C, viruses that have dried on surfaces can usually last two to eight hours. At 22 ° C they survive in the excrement as well as in the tissues of deceased animals and in water for at least four days, at a temperature of 0 ° C for more than 30 days and in ice they are infectiously infectious. Above body temperature, however, the environmental stability of A / H5N1 also decreases very significantly. At 56 ° C the viruses are inactivated within 3 hours and at 60 ° C within 30 minutes. From 70 ° C, the viruses are destroyed and thus finally lose their infectivity .

Classification of the subtypes

3D model of an influenza virus

Influenza viruses belong taxonomically to the Orthomyxoviridae family, which includes five genera: Influenza A , Influenza B , Influenza C , Thogotovirus and Isavirus . Birds are only attacked by influenza A viruses and their variants or subtypes.

Constant gene changes (mutations) constantly create new variants of the flu virus. These are divided into sub-types according to certain surface properties. So far, 16 H subtypes and 9 N subtypes have been recognized serologically . The subtype A / H5N1, for example, has variant 5 of hemagglutinin (H5) and variant 1 of neuraminidase (N1) on its surface . These sub-types usually only infect certain hosts at a time , while a wider range of infection vectors can spread them without these animals becoming ill. The subtype A / H5N1 is more aggressive in humans than the A / H7N7 or SARS .

Within the subtype A / H5N1 also be more clades (engl. Clades ) distinguished, which are further divided into individual stems and in its relatively high virulence partially differ significantly. The Asian H5N1 variant (A / Vietnam / H5N1 / 1203/2004) was particularly noticeable due to its increased aggressiveness and pathogenicity . According to a Hong Kong research group, this variant releases certain inflammatory substances ( cytokines , especially interleukin 6 ) in the lungs to a particularly high degree , which normally activate the body's immune response against invading pathogens. However, this excessive (excessive) cytokine release ( cytokine storm ) leads to an overreaction of the immune system and thus to additional immune pathogenesis through the destruction of the lung tissue in particular and usually quickly to severe toxic shock and multi-organ failure .

In spring 2008 the World Health Organization (WHO) announced a new, uniform set of rules for the naming of the H5N1 strains. In the future, the location should no longer be part of the name; since then, for example, the Fujian tribe has been referred to as clade 2.3.4 and the Qinghai tribe as clade 2.2. The main aim of the set of rules is to facilitate international understanding of the numerous variants of A / H5N1.

Detection methods

Graduated virological diagnostics are usually used to detect A / H5N1 .

Rapid tests are available for the detection of influenza A viruses, which are also able to detect A / H5N1 viruses. Nose and throat swabs are taken as test material. The first results are then available within 20 to 30 minutes.

Using the antibodies commonly used in serology, secondary antibodies marked with colloidal gold particles can also be used to differentiate the serotypes in the transmission electron microscope in less than half an hour.

For a - more precise - laboratory evidence, the highly conserved matrix gene (M gene), which is highly conserved due to the functional specifications of the two proteins generated by alternative splicing, is attempted from an organic sample with the aid of the polymerase chain reaction (qRT-PCR) A virus occurs. Throat and cloacal swabs, which can be obtained from dead as well as living animals, are usually used as sample material. Tissue samples (e.g. lungs, trachea, brain) can also be taken from dead animals, which allow a more reliable analysis result due to the higher viral load.

If an infection with influenza A virus was confirmed in this way, the PCR is used again to detect hemagglutinin variant 5 (H5) and - in parallel - variant 1 of neuraminidase (N1) using selected recognition sequences . If these two findings are also positive, the third step is a molecular biological differentiation between low pathogenic (LPAI) and highly pathogenic (HPAI) influenza viruses based on the DNA sequence of the hemagglutinin cleavage site obtained by RT-PCR and DNA sequencing . This can be done by sequencing the H5 cleavage site or by probe hybridization in a qRT-PCR. The following example shows a DNA and amino acid sequence of A / H5N1: AGA GAG AGA AGA AGA AAA AAG AGA * GGA CTA TTT / RERRRKKR * GLF. The basic amino acid sequence (arginine, lysine) at the cleavage point (*) indicates a highly pathogenic influenza virus. The distinction between highly pathogenic and low pathogenic influenza viruses can also be made by determining the pathogenicity index in animal experiments.

In addition to molecular biological diagnostics - at least in the case of an initial outbreak - the virus is isolated in the embryonated hen's egg . Classically, the evaluation is carried out by means of the hemagglutination inhibition test , which proves the ability of the influenza viruses to agglutinate erythrocytes. The surface protein hemagglutinin is then subtyped using the hemagglutination inhibition test against polyclonal reference sera. Similarly, the neuraminidase type can be determined using the neuraminidase inhibition test.

Serological tests are also used to detect antibodies against influenza viruses. These tests can also record diseases that have occurred in the past, since antibodies (especially against H5 and N1) and cytotoxic T cells (especially against NP and PB1) can be detected in the convalescent after the disease . The most widely used method is the ELISA , which, due to its simple handling and automatability, allows the investigation of large sample quantities at low costs. Such ELISA tests can detect both subtype-specific (H5) and virus-specific influenza A viruses.

The hemagglutination inhibition test, in combination with reference antigens, can determine antibodies against hemagglutinin types H1 to H16.

When plaque assay for influenza virus which is mostly cell line MDCK (Engl. Madine Darby Canine Kidney ) used.

origin

According to a study published in February 2006, Chinese researchers apparently succeeded in narrowing down the origin of the highly pathogenic H5N1 variant. From early 2004 to mid-2005, the researchers examined more than 51,000 ducks, geese and chickens in markets in six south-east Chinese provinces and found that around 2 out of 100 ducks and geese carried the virus unobtrusively. The virus was also found in some chickens (0.26%). They were also able to detect three regional clusters (differences) in the genes of the viruses, with a focus on the southern Chinese provinces of Guangdong , Hunan and Yunnan . According to the researchers, these differences indicate that the viruses had already had a long time to change. The Chinese researchers suspect that A / H5N1 has been circulating in southern China for more than 10 years, although the first major outbreak in poultry farming did not occur until 1997. In contrast to the official political institutions of China, the researchers also assume that the viruses in southern China have developed into the highly pathogenic variant that exists today and from there to the neighboring countries; Virus samples from Thailand are very similar to the samples from Guangdong. The considerable degree of infection of the Chinese poultry stocks with A / H5N1 is attributed by researchers to the vaccination of many animals against avian influenza viruses, which is common there, as a result of which many virus carriers are protected from conspicuous disease symptoms.

Smears from the nose of 702 asymptomatic Indonesian pigs analyzed between 2005 and 2007 revealed that 52 animals (7.4%) were infected with A / H5N1 viruses. The viruses each showed a great similarity with comparison samples which had been obtained at the same time in the vicinity due to H1N1 outbreaks among poultry; From this the authors derived the assumption that the viruses had passed from poultry to pigs. One of the virus isolates (A / swine / Banten / UT3062 / 2005) was able to bind to a receptor that is found in the nose of both birds and humans due to a mutation. This mutation was not previously known from virus samples from birds, but presumably an adaptation to this species that occurred in pigs; the mutation could possibly serve as a marker for assessing the pandemic potential of other H5N1 isolates.

Genetic changes

The A / H5N1 subtype is also considered to be particularly aggressive (HPAI, Highly Pathogenic Avian Influenza) from the findings already presented above . The virologist Robert G. Webster highlights a special property of this subtype that, like variant H7 and unlike all other subtypes, it first affects the lungs and then spreads throughout the body and in birds it also destroys the heart, liver and brain. That is why it kills infested birds very quickly today, which do not belong to its virus reservoir, and because of its pathogenic properties it is closely monitored by scientists for interdependencies with other strains and transgressions of the species barrier .

Before the aforementioned and two other proven genetic changes (which, according to experts, happened at the end of 1996 / beginning of 1997 and 2003), the pathogen had already appeared several times in Europe, but it was considered to be less aggressive. Even today, isolated wild birds are found that are infected with this less pathogenic variant but show hardly any symptoms of the disease, for example in 2004 in France and in mid-November 2005 in a duck near Padua .

First findings

According to a report in the journal Nature , one of the genetic changes (relating to an amino acid at position 223 of the hemagglutinin receptor protein), which were initially detected in Hong Kong and Vietnam in 2003 and then again in early 2006 in children who died in Turkey , allows the viruses to become infected more easily than bind to human cells beforehand. A second genetic change, also proven in the Turkish children, causes the exchange of glutamic acid for lysine in position 627 of its polymerase protein, which the viruses use to replicate their genetic material . This mutation has also been detected earlier elsewhere, but never in combination with the mutation at position 223 of the hemagglutinin receptor protein. It was also detected in the Netherlands in 2003 when a man died of an H7N7 infection there, and is one of a total of 10 mutations that are said to have given the Spanish flu virus the ability to pass through to humans largely unhindered. The change in the polymerase protein allows the viruses to survive longer than before in a person's relatively cool nose, while the changed receptor protein enables easier binding to the mucous membrane cells of the nose. The World Health Organization had relativized these findings in February 2006 to the extent that it pointed out that it was not known for sure which specific mutations were necessary for A / H5N1 to pass more easily and sustainably from person to person.

According to a report in the New Scientist magazine , British researchers assumed in 2008 that two specific mutations in the H5 protein were already capable of making it much easier for the viruses to bind to the mucous membrane cells of mammals. So far, none of these mutations has been detectable in the circulating virus strains. From this one can conclude that neither of these changes has a selective advantage for the viruses, which minimizes the risk that both changes occur at the same time.

A research team led by James Stevens from the Scripps Research Institute in La Jolla , California , expressed the opinion in 2006 that the influenza A / H5N1 viruses are now more similar to the pathogens of human influenza than previously thought. The surface proteins of A / H5N1 would now show striking similarities with those of the Spanish flu pathogen . In the case of the H5N1 strain isolated from ducks in 1997, they found fewer similarities. They therefore feared that only a few more changes on the surface of the A / H5N1 viruses would be enough to make them highly dangerous for humans.

Controversial experiments with ferrets

In an experiment carried out by Dutch researchers led by Ron Fouchier from the Erasmus Medical Center in Rotterdam, it was possible in 2011 to infect ferrets with A / H5N1 viruses and then to transfer the viruses from the sick animals to their own species. In the autumn and winter of 2011, the researchers involved remained uncontested by reports that the virus spread through the air after the tenth such transmission and infected ferrets in neighboring cages, which soon perished. In influenza research, ferrets are considered to be an animal model similar to humans, since the distribution and specificity of the hemagglutinin receptors that the influenza virus uses to bind to and fuse with the cell are similar. This consists of sialic acid- modified proteins, which in ferrets and humans are linked to galactose in the upper respiratory tract via an α-2,6- glycosidic bond ; in the avian strains this is frequently α-2,3-linked. In humans, however, the α-2,3 linkage occurs primarily in the lower respiratory tract, which makes the release of newly formed virions by coughing and thus also the transmission more difficult. Due to these different links, avian influenza strains ( bird flu H5N1 ) can only be transmitted poorly to and through humans. It can therefore be assumed that the results obtained in the tests with the ferrets can also be applied to humans. The original strain of the virus had already shown three mutations that are known to adapt A / H5N1 to a stay in mammals. The tenfold transmission had added two new mutations which, in combination with the three initial ones, turned out to be fatal. All five mutations had previously been individually detected in birds. From the end of 2011 this experiment led to a discussion about bio-terrorist risks, if details of the study were published.

At the end of January 2012, 39 influenza researchers announced that they would voluntarily interrupt their work for 60 days and refrain from further experiments on the transferability of A / H5N1. This should give the health authorities time to adopt stricter security measures. A few days later, members of the US National Science Advisory Board for Biosecurity (NSABB) declared that the research results should not be published in full. The NSABB had been commissioned by the US government to submit a risk assessment regarding dual use . At the same time, the government of the Netherlands had insisted that Ron Fouchier had his planned publication officially approved as an "export" within the framework of EU regulations on preventing the proliferation of weapons of mass destruction .

In February 2012, Ron Fouchier corrected the alleged results of his study later published in Science, which had been discussed until then : In fact, the mutated virus did not spread in aerosols like a pandemic or seasonal virus. The ferrets only perish if the virus was specifically introduced into the windpipe or nasal passages. At the beginning of April 2012, the US National Science Advisory Board for Biosecurity gave permission to publish the research results.

Also Yoshihiro Kawaoka was from the School of Veterinary Medicine of the University of Wisconsin-Madison , details of a similar study known which had been also examined by the US Agency for biosafety; This study, published in Nature in May 2012 , also found that H5N1 viruses used in ferrets were more easily transmitted from animal to animal.

Control and protection measures

Vaccine development

Vaccines against a virus can be developed more quickly the more precisely the researchers know about its structure. Therefore, samples of newly emerged virus variants have been passed on to research institutions free of charge by the national health authorities through the World Health Organization (WHO) for decades . From the end of 2006, however, Indonesia refused to make its virus samples available to the WHO for several months because the country would not benefit from its actions in the event of a pandemic: All major vaccine producers are based in industrialized countries , which are expected to issue trade bans after a pandemic broke out would to provide their own population with the then presumably scarce vaccine. In May 2007 the WHO made financial commitments, whereupon Indonesia announced that it would resume its cooperation with the WHO. However, this promise was only made more concrete in May 2008 when Indonesia announced that it would make the relevant data of its virus samples available to the WHO in a newly established online database. However, virus samples are usually required for vaccine development, and Indonesia continued to hamper release. It was not until April 2011 that the WHO reported a “landmark agreement”, according to which vaccine producers - as compensation for passing on virus samples - made at least ten percent of the vaccine quantity produced in a pandemic available to the WHO for distribution to regions in need or allow the royalty-free production of vaccines in developing countries . In addition, the researchers from the industrialized countries who are involved in the evaluation of virus samples should “actively search” for colleagues from the developing countries with whom they could jointly publish original scientific papers in renowned specialist journals.

Active immunization

Adenovirus versus other viruses

At the beginning of February 2006 , both a research team led by Andrea Gambotto from the University of Pittsburgh and a group led by Suryaprakash Sambhara from the Centers for Disease Control and Prevention (CDC) in Atlanta , both USA , produced a new type of prototype of an avian flu system that has so far been reliably effective in mice and chickens. Vaccine against A / H5N1 presented.

Andrea Gambotto's employees took harmless cold viruses ( adenoviruses ) and built into them a special gene of the A / H5N1 virus, which produces (expresses) parts or the full version of a certain protein of the bird flu virus on the virus surface . This is what is known as haemagglutinin (HA), which is found on the surface of all flu viruses and helps them to dock with the host cells so that they can then penetrate them.

Hemagglutinin

In mice treated with this genetically engineered vaccine, no pathogens were detectable six days after the subsequent infection with the virus variant A / Vietnam / H5N1 / 1203/2004, and immunity to A / H5N1 was also observed after 70 days . Chickens were protected from H5N1 avian flu after just 21 days if this vaccine was injected under the skin (subcutaneously). According to the scientists, the active ingredient is based on genetically modified components of the living virus and therefore activates the immune system more effectively than conventional flu vaccinations .

Since the modified viruses used for the new vaccine are not grown in fertilized chicken eggs like the conventional flu vaccines, but in cell cultures, they can now be produced very quickly and in large quantities and just as quickly tailored to virus changes that have occurred. This made a simplified and accelerated vaccine production possible. According to their own information, the scientists in Pittsburgh only needed 36 days to produce their serums .

The researchers working with Suryaprakash Sambhara in Atlanta also used the common cold virus as a “transporter” for a gene from the virus. In them, all mice treated with this vaccine survived a subsequent infection with A / H5N1, with all viruses no longer being detectable in the lungs of the animals within four days. According to the scientists, their vaccine can be used for various sub-variants of the avian flu virus and can be produced by employees within five to seven weeks.

However, experts believe that many more time-consuming tests are necessary to an effective vaccination of humans is possible. It could take three to four years for the vaccines to be ready for the market.

In early 2006, a research team led by John Treanor from the University of Rochester , New York State, tested a vaccine against A / H5N1 for its effectiveness in humans. In contrast to the dose of 15 micrograms used for vaccines against human influenza, the test subjects now received two vaccinations of either 7.5 or 90 micrograms four weeks apart from these scientists. In the high-dose group, 54 percent of the subjects achieved an antibody level determined by blood samples after the second vaccination, which experts believe will probably protect against illness. However, the researcher Gregory Poland from the Mayo Clinic in Rochester rates the protective effect achieved by his colleagues in humans as weak or at most mediocre. He also points out that the different variants of A / H5N1 that are now in circulation will certainly require several different vaccines . Therefore, Poland is much more likely to see a need to promote more modern vaccine production processes using cell cultures.

In 2005, a team led by Thomas Mettenleiter from the Friedrich Loeffler Institute on the island of Riems developed the prototype for a vaccine against H5N1 bird flu, which protects chickens from this viral disease and, unlike conventional vaccines, allows vaccinated and infected animals to be clearly distinguished.

For their experiments, the researchers modified an existing vaccine virus against Newcastle disease , which is caused by an RNA virus of the Paramyxoviridae family, the Newcastle Disease Virus (NDV). For this purpose, a mutant of the hemagglutinin gene of an H5N2 influenza virus was integrated into the NDV genome by reverse genetics ; After a transfection , active virus particles could be isolated which, in addition to the NDV surface proteins, also had the H5 protein. The efficiency of the experiments in chickens indicated that the vaccine protects against both Newcastle disease and H5N1 avian influenza, as the animals treated in this way subsequently survived high levels of avian influenza and ND viruses and developed antibodies against both pathogens . Since animals vaccinated with this vaccine only produce antibodies against proteins of the ND virus and the hemagglutinin of the influenza virus, vaccinated animals can be distinguished from unvaccinated animals. For this purpose, an attempt is made by means of ELISA to detect antibodies against the influenza nucleoprotein, which is not present in the vaccine virus. If the proof is positive, this indicates an infection of the animal with an influenza virus. The new vaccine is to be checked in further tests, but can be approved around 2011 at best.

According to a research report by Gary Nabel's team from the Vaccine Research Center of the National Institutes of Health in Bethesda (USA), it would be quite possible to develop a vaccine against a H5N1 influenza pandemic that may break out in the future, even before a human is Directly transmissible variant of the bird flu virus emerged in the environment. The scientists have focused on a small area of hemagglutinin - molecule concentrates a dangerous H5N1 variant laboratory with which the pathogens attach to the surface of the host cell and enter into it. It was possible to prove that the host's binding partner, the so-called sialic acid receptor , consists of a different salic acid variant in birds and humans. It is therefore assumed that adapting the HA binding site to this difference on the virus side represents an important and necessary step from avian to human virus. In anticipation of possible evolutionary steps , the researchers used targeted mutations to hold several viruses with their variant of the virus with different adaptation of the HA binding site to the human SA receptor. In further experiments, they found that, as an immune reaction to these new virus variants, mice also produced antibodies that were directed against the specific binding site of the respective virus.

It was then possible to observe that these antibodies brought about good immune protection against the virus variant used in each case. The modified laboratory viruses could thus be suitable as vaccination viruses. A development of resistance to such a vaccine stands in the way of the fact that the pathogen cannot change the HA binding site at will, since this also has an important function in its life cycle. According to the researchers, the process they have tested can be used to produce a number of vaccine prototypes that can be used very quickly in an emergency and with which large quantities of vaccine can be produced for nationwide vaccinations.

New vaccines

Daronrix is a pandemic vaccine with inactivated influenza viruses from the manufacturer GlaxoSmithKline Biologicals. Similar to Prepandrix as a prepandemic vaccine, it is a split vaccine .

As the first vaccine of its kind, it was approved with the virus strain A / H5N1 (A / Vietnam / 1194/2004) by the European Medicines Agency on March 21, 2007 for the 27 EU countries, enabled by Directive CPMP / VEG / 4986/03 to replace the contained strain with the actually circulating strain in the event of a pandemic.

Focetria is a pandemic vaccine with the adjuvant MF59 from the Swiss company Novartis Vaccines and Diagnostics. In preliminary studies and a first application for approval, Influenza A / H5N3 and Influenza A / H9N2 were used , then a new application was converted to Influenza A / H5N1.

As the second vaccine of its kind, it was approved with the virus strain Influenza A / H5N1 (A / Vietnam / 1194/2004) by the European Medicines Agency on May 8, 2007 for the 27 EU countries plus Norway and Iceland, the CPMP / VEG guideline / 4986/03 makes it possible to replace the contained strain with the actually circulating strain in the event of a pandemic.

Passive immunization

At the beginning of 2006, a research team led by Jaihai Lu from Sun Yat-sen University in Guangzhou , People's Republic of China , developed a passive vaccination against A / H5N1 for mice. The researchers infected horses with attenuated A / H5N1 viruses and then recovered the antibodies against these pathogens from their blood. Then they cut a certain part of these antibodies with an enzyme , which is not rejected by the immune system of the mice. This antibody fragment was then injected into mice that had been infected 25 hours previously with a dose of H5N1 virus that would normally be fatal for them. According to the Chinese researchers, 100 micrograms of the antibody fragments protected all mice from what would otherwise be certain death, because all animals in the control group that were only treated with a placebo usually died after about nine hours. Experts, however, express considerable concerns with regard to the possible use of this method in humans, since such a passive vaccine could indeed be produced more quickly than an active one, but on the other hand it would be less well tolerated and only cause less immune protection.

Genetic Approaches

British scientists from the University of Cambridge , University of Edinburgh and the Veterinary Laboratories Agency have transgenic chickens developed that the avian influenza can not be transmitted. The chickens were fitted with an expression cassette which produced a piece of RNA that served as a bait for polymerase. Instead of binding to the virus genome and thereby helping the virus to replicate, the polymerase then clings to this bait. The transgenic chickens still died from avian influenza, but no longer infected other chickens. The aim is the complete immunization of chickens against A / H5N1.

Reporting requirement

In Austria, infections with the influenza virus A / H5N1 or another bird flu virus are also a notifiable disease according to Section 1 (1) of the 1950 Epidemic Act . The reporting obligation relates to suspected cases, illnesses and deaths. Doctors and laboratories, among others, are obliged to report this ( Section 3 Epidemics Act).

In Germany, “zoonotic influenza” is a notifiable disease according to Section 6 (1) of the Infection Protection Act (IfSG). You are required to report by name in the event of suspicion, illness or death. It mainly affects the diagnosing physicians (cf. § 8 IfSG). In addition, the direct detection of (any) influenza viruses must be reported by name in accordance with Section 7 IfSG, if the evidence indicates an acute infection. This reporting obligation for the pathogen primarily affects laboratories and their lines (see also § 8 IfSG).

See also

literature

  • Xiyan Xu et al. a .: Genetic characterization of the pathogenic Influenza A / Goose / Guangdong / 1/96 (H5N1) Virus: Similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreak in Hong Kong. In: Virology. Volume 261, No. 1, 1999, pp. 15-19, doi: 10.1006 / viro.1999.9820 , full text
  • M. Hugh-Jones: Biological disasters of animal origin: the role and preparedness of veterinary and public health services. In: Revue scientifique et technique (International Office of Epizootics). Volume 25, Number 1, April 2006, pp. 421-7, 429, PMID 16796065 (Review).

Web links

Individual evidence

  1. ↑ ICTV Master Species List 2018b.v2 . MSL # 34, March 2019
  2. ↑ a b ICTV: ICTV Taxonomy history: Akabane orthobunyavirus , EC 51, Berlin, Germany, July 2019; Email ratification March 2020 (MSL # 35)
  3. ↑ Negative Sense RNA Viruses: Orthomyxoviridae , in: ICTV 9th Report (2011)
  4. ↑ see avian flu H5N1 # Animal-to-animal transmission routes and distribution of H5N1
  5. ↑ Josanne H. Verhagen et al. : How a virus travels the world. In: Science . Volume 347, No. 6222, 2015, pp. 616–617, doi: 10.1126 / science.aaa6724
  6. ↑ Xiyan Xu et al. : Genetitic characterization of the pathogenic Influenza A / Goose / Guangdong / 1/96 (H5N1) Virus: Similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreak in Hong Kong. In: Virology. Volume 261, 1999, pp. 15-19, full text
  7. ↑ Yoshi Kawaoka , Robert G. Webster : Sequence requirements for cleavage activation of influenza virus hemagglutinin expressed in mammalian cells. In: Proceedings of the National Academy of Sciences of the United States of America . Volume 85, Number 2, January 1988, pp. 324-328, ISSN  0027-8424 . PMID 2829180 . PMC 279540 (free full text).
  8. ↑ S. Fukuyama, Y. Kawaoka: The pathogenesis of influenza virus infections: the contributions of virus and host factors. In: Current Opinion in Immunology . Volume 23, Number 4, August 2011, pp. 481-486, ISSN  1879-0372 . doi: 10.1016 / j.coi.2011.07.016 . PMID 21840185 . PMC 3163725 (free full text).
  9. ^ I Ramos, A. Fernandez-Sesma: Innate immunity to H5N1 influenza viruses in humans. In: Viruses. Volume 4, Number 12, December 2012, pp. 3363-3388, ISSN  1999-4915 . PMID 23342363 . PMC 3528270 (free full text).
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This version was added to the list of articles worth reading on June 2, 2006 .