MedWorm: H2N2

Safety, immunogencity, and efficacy of a cold-adapted A/Ann Arbor/6/60 (H2N2) vaccine in mice and ferrets.

Virology — Tue, 22 Dec 2009 00:00:00 +0100

Authors: Chen GL, Lamirande EW, Jin H, Kemble G, Subbarao K We studied the attenuation, immunogenicity and efficacy of the cold-adapted A/Ann Arbor/6/60 (AA ca) (H2N2) virus in mice and ferrets to evaluate its use in the event of an H2 influenza pandemic. The AA ca virus was restricted in replication in the respiratory tract of mice and ferrets. In mice, 2 doses of vaccine elicited a >4-fold rise in hemagglutination-inhibition (HAI) titer and resulted in complete inhibition of viral replication following lethal homologous wild-type virus challenge. In ferrets, a single dose of the vaccine elicited a >4-fold rise in HAI titer and conferred complete protection against homologous wild-type virus challenge in the upper respiratory tract. In both mice and ferrets, the AA ca virus prov...

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Seasonal, Avian, and Novel H1N1 Influenza: Prevention and Treatment Modalities (December).

The Annals of Pharmacotherapy — Tue, 17 Nov 2009 00:00:00 +0100

CONCLUSIONS: Influenza subtypes continue to change, causing disease in animals and humans. Utilization of immunization and antiviral treatment options are available to prevent, treat, and contain the spread of this infection. PMID: 19920156 [PubMed - as supplied by publisher] (Source: The Annals of Pharmacotherapy)

New WHO Criteria To Qualify Flu Viruses As Pandemic Strains

Health News from Medical News Today — Wed, 04 Nov 2009 08:00:00 +0100

An editorial published today in BMJ Clinical Evidence reports that more flu viruses could qualify as pandemic strains as a result of recent changes to the World Health Organisation (WHO) criteria for a flu pandemic. A change from, for example, A [H2N2] influenza to A [H3N2] is a process known as a "shift". (Source: Health News from Medical News Today)

The influence of the multi-basic cleavage site of the H5 hemagglutinin on the attenuation, immunogenicity and efficacy of a live attenuated influenza A H5N1 cold-adapted vaccine virus.

Virology — Mon, 12 Oct 2009 23:00:00 +0100

Authors: Suguitan AL, Marino MP, Desai PD, Chen LM, Matsuoka Y, Donis RO, Jin H, Swayne DE, Kemble G, Subbarao K A recombinant live attenuated influenza virus DeltaH5N1 vaccine with a modified hemagglutinin (HA) and intact neuraminidase genes from A/Vietnam/1203/04 (H5N1) and six remaining genome segments from A/Ann Arbor/6/60 (H2N2) cold-adapted (AA ca) virus was previously shown to be attenuated in chickens, mice and ferrets. Evaluation of the recombinant H5N1 viruses in mice indicated that three independent factors contributed to the attenuation of the DeltaH5N1 vaccine: the attenuating mutations specified by the AA ca loci had the greatest influence, followed by the deletion of the H5 HA multi-basic cleavage site (MBS), and the constellation effects of the AA genes acting in concer...

Residual immunity in older people against the influenza A(H1N1) - recent experience in northern Spain

Eurosurveillance latest news — Thu, 01 Oct 2009 00:00:00 +0100

The 2009 pandemic influenza A(H1N1) virus has a higher incidence in children and young adults, a pattern that has also been reported in seasonal influenza caused by the influenza A(H1N1) virus. We analysed age at infection in symptomatic patients with influenza in the Basque Country (northern Spain), reported through the sentinel influenza surveillance system which monitors 2.2-2.5% of the population. Between September 1999 and August 2009, influenza A(H3N2) or seasonal influenza A(H1N1) was detected in 941 patients, and from April to August 2009, pandemic influenza A(H1N1) was detected in 112 patients. The H3/H1 seasonal influenza ratio was between 3.3 and 3.4 in the under 60 year-olds, but 9.8 in older individuals, suggesting that people born before 1950 have residual immunity against th...

Molecular Detection of a Novel Human Influenza (H1N1) of Pandemic Potential by Conventional and Real-Time Quantitative RT-PCR Assays [Brief Communications]

Clinical Chemistry — Mon, 27 Jul 2009 23:00:00 +0100

Conclusions: These assays appear useful for the rapid diagnosis of cases with the novel H1N1 virus, thereby allowing better pandemic preparedness. (Source: Clinical Chemistry)

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H1N1 traced to 1918 pandemic

NHS News Feed — Tue, 21 Jul 2009 16:47:00 +0100

This article was written by D M Morens and colleagues from the National Institute of Allergy and Infectious Diseases, Bethesda, in the US. It was published in the New England Journal of Medicine. No potential conflicts of interest were reported. A related article on the evolution of the current pandemic strain of the H1N1 virus was also published in the same issue and has been covered in Behind the Headlines. What kind of study was this? This was a review article written by acknowledged experts in the field, explaining the lineage of the pandemic flu virus seen in 1918 and relating it to the emergence of the pandemic H1N1 strain currently circulating. What do the researchers say? The researchers explain that descendents of the H1N1 influenza A virus that caused the pandemic of 1918�...

The history of swine flu

NHS News Feed — Tue, 30 Jun 2009 18:30:00 +0100

The Independent says that “the swine flu pandemic might not have happened had it not been for the accidental release of the same strain of influenza virus from a research laboratory in the late 1970s.” The news comes from a medical article which analysed the history of the influenza A H1N1 virus, including the recent development of swine flu seen around the world. The reports say that the H1N1 influenza strain was responsible for a flu pandemic in 1977, but before this it had not been found in humans for more than 20 years. By looking at the genetic makeup of the 1977 virus, researchers have found that it was similar to a strain that was circulating in 1950. This 1950s strain would have been stored in labs and researchers have suggested that the re-emergence of the virus in 1977 “was...

Extant blood samples to deduce the strains of the 1890 and possibly earlier pandemic influenzas

Medical Hypotheses — Sun, 24 May 2009 23:00:00 +0100

Summary: Influenza outbreaks in 1918, 1957 and 1968 caused some of the highest infectious disease mortality in the 20th century. In particular the 1918 pandemic caused more than 50 million deaths worldwide—the most deaths caused by any infectious disease ever in human history. Influenza pandemics in 1890 and earlier in the 19th century and back until at least the 16th century also caused non-trivial mortality. The excessively high mortality from flu in these years is thought to be due to major antigenic shifts in influenza strains, as opposed to smaller drifts in flu strains in years between pandemics. It is also thought that flu strains cycle naturally; however, as the 1918 pandemic was caused by an H1N1 strain, the 1957 pandemic by an H2N2 strain and the 1968 pandemic by an H3N2 flu, t...

Functional significance of the hemadsorption activity of influenza virus neuraminidase and its alteration in pandemic viruses

Archives of Virology — Thu, 21 May 2009 06:21:03 +0100

Abstract Human influenza viruses derive their genes from avian viruses. The neuraminidase (NA) of the avian viruses has, in addition to the catalytic site, a separate sialic acid binding site (hemadsorption site) that is not present in human viruses. The biological significance of the NA hemadsorption activity in avian influenza viruses remained elusive. A sequence database analysis revealed that the NAs of the majority of human H2N2 viruses isolated during the influenza pandemic of 1957 differ from their putative avian precursor by amino acid substitutions in the hemadsorption site. We found that the NA of a representative pandemic virus A/Singapore/1/57 (H2N2) lacks hemadsorption activity and that a single reversion to the avian-virus-like sequence (N367S) restores hemad...

Characteristics of arbidol-resistant mutants of influenza virus: Implications for the mechanism of anti-influenza action of arbidol.

Antiviral Research — Fri, 21 Nov 2008 05:00:00 +0100

Authors: Leneva IA, Russell RJ, Boriskin YS, Hay AJ The antiviral drug arbidol (ARB), which is licensed in Russia for use against influenza, is known to inhibit early membrane fusion events in influenza A and B virus replication. To investigate in more detail the target and mechanism of ARB action we generated and studied the characteristics of ARB-resistant influenza virus mutants. Observations of the ARB susceptibility of reassortants between A/Singapore/1/57(H2N2) and A/chicken/Germany/27(H7N7, "Weybridge" strain) and of mutants of the latter virus identified the virus haemagglutinin (HA) as the major determinant of ARB sensitivity. ARB-resistant mutants, selected from the most sensitive reassortant, possessed single amino acid substitutions in the HA2 subunit which caused an increa...

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Genetic characterization and protective immunity of cold-adapted attenuated avian H9N2 influenza vaccine.

Vaccine — Fri, 03 Oct 2008 04:00:00 +0100

Authors: Lee JS, Kim HS, Seo SH H9N2 influenza viruses are endemic in many Asian countries including China and Korea, and cause a considerable economic loss to chicken industry by reduction in egg production and about 30% mortality. Here we developed live cold-adapted attenuated H9N2 influenza vaccine by adaptation of viruses in hen's eggs at 25 degrees C. Genetic analysis shows that the cold-adapted H9N2 (A/Chicken/Korea/S1/03) viruses contain a total of 44 amino acid substitutions, of which 7 amino acids are identical to the loci identified in the cold-adapted H2N2 (A/Ann Arbor/6/60) vaccine strain compared to genes in wild-type H9N2 (A/Chicken/Korea/S1/03) influenza viruses. When cold-adapted H9N2 (A/Chicken/Korea/S1/03) influenza viruses were inoculated in layers viruses were detec...

Prevalence of avian influenza viruses, Borrelia garinii, Mycobacterium avium, and Mycobacterium avium subsp. paratuberculosis in waterfowl and terrestrial birds in Slovakia, 2006.

Avian Pathology — Thu, 18 Sep 2008 17:52:35 +0100

Authors: Gronesova P, Ficova M, Mizakova A, Kabat P, Trnka A, Betakova T The prevalence of Borrelia, Mycobacteria and avian influenza virus (AIV) infections, together with the distribution of different AIV subtypes, was studied in migratory waterfowl and terrestrial birds trapped in three localities in Slovakia during 2006. Samples obtained from waterfowl captured in the Senianske Ponds area of Eastern Slovakia showed the highest diversity of AIV isolates. A total of 13 different subtypes were detected in 19 samples from this location (H1N2, H2N2, H3N2, H6N6, H7N6, H9N2, H9N5, H9N6, H10N5, H10N6, H12N6, H13N6, and H16N6). H3N5 virus was detected in 50% of passerines testing positive for AIV in the Parizske Wetlands, with H7N2, H9N2, H9N5, H12N1, and H13N2 infections also recorded at th...

Homologous recombination evidence in human and swine influenza A viruses.

Virology — Wed, 20 Aug 2008 04:00:00 +0100

This study reports several significant evidence demonstrating that homologous recombination also takes place between influenza A viruses in human and swine lineages. Moreover, in a mosaic descended from swine H1N1 subtype and human H2N2, we found that its minor putative parent might be a derivative from the human cold-adapted vaccine lineage, which suggests that live vaccine is capable of playing a role in genetic change of influenza A virus via recombination with circulating viruses. These results would be important for knowing the molecular mechanism of mammal influenza A virus heredity and evolution. PMID: 18721995 [PubMed - as supplied by publisher] (Source: Virology)

Effects of single-point amino acid substitutions on the structure and function neuraminidase proteins in influenza A virus.

Microbiology and Immunology — Thu, 03 Jul 2008 15:39:44 +0100

Authors: Yano T, Nobusawa E, Nagy A, Nakajima S, Nakajima K In order to clarify the effect of amino acid substitutions on the structure and function of the neuraminidase (NA) protein of influenza A virus, we introduced single-point amino acid substitutions into the NA protein of the A/Tokyo/3/67 (H2N2) strain using PCR-based random mutation. The rate of tolerant random one amino acid substitutions in the NA protein was 47%. Rates of tolerant substitutions for the stalk and for the surface and inner portion of the head region of the NA protein were 79, 54, and 19%, respectively. Deleterious changes, such as those causing the NA protein to stop at the Golgi/endoplasmic reticulum, were scattered throughout the protein. On the other hand, the ratio of mutations with which the NA protein lo...

Confronting an influenza pandemic with inexpensive generic agents: can it be done?

The Lancet Infectious Diseases — Tue, 15 Apr 2008 04:00:00 +0100

Authors: Fedson DS Avian influenza A H5N1 presents a serious and possibly imminent pandemic threat. In such an event, adequate supplies of affordable vaccines and antiviral agents will be unavailable to most people in the world. In view of the overwhelming need for effective alternatives, generic agents that target the host immune response or the pandemic virus should be considered. Many scientists doubt the effectiveness of these agents. Nonetheless, several studies suggest that statins improve outcomes in patients with bacteraemia and pneumonia and might be similarly effective against influenza. An experimental study has shown that the fibrate gemfibrozil, a peroxisome proliferator-activated receptor (PPAR) alpha agonist, reduces mortality in H2N2 influenza virus-infected mice. There...

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An exploratory method for estimating the changing speed of epidemic waves from historical data

International Journal of Epidemiology — Thu, 31 Jan 2008 05:00:00 +0100

Conclusions The new measure of wave velocity appears to be applicable to those historical time series where breakdown into regional or local areas is available. The study is being extended to (i) other countries where similar influenza time series are available and (ii) to other diseases within Iceland. (Source: International Journal of Epidemiology)

Healthy Human Subjects Have CD4+ T Cells Directed against H5N1 Influenza Virus.

Journal of Immunology — Thu, 24 Jan 2008 10:28:50 +0100

Authors: Roti M, Yang J, Berger D, Huston L, James EA, Kwok WW It is commonly perceived that the human immune system is naive to the newly emerged H5N1 virus. In contrast, most adults have been exposed to influenza A H1N1 and H3N2 viruses through vaccination or infection. Adults born before 1968 have likely been exposed to H2N2 viruses. We hypothesized that CD4(+) T cells generated in response to H1N1, H3N2, and H2N2 influenza A viruses also recognize H5N1 epitopes. Tetramer-guided epitope mapping and Ag-specific class II tetramers were used to identify H5N1-specific T cell epitopes and detect H5N1-specific T cell responses. Fifteen of 15 healthy subjects tested had robust CD4(+) T cell responses against matrix protein, nucleoprotein, and neuraminidase of the influenza A/Viet Nam/1203/...

Automated extraction of avian influenza virus for rapid detection using real-time RT-PCR.

Journal of Clinical Virology — Sat, 15 Sep 2007 04:00:00 +0100

CONCLUSION: The main advantages of automated robotic viral nucleic acid extraction are high throughput processing; hands-free operation; and reduction in human and technical error. This study demonstrates successful detection of influenza A virus with magnetic beads utilizing the Qiagen MagAttract cell kit on a BioRobot M48 platform. PMID: 17875401 [PubMed - as supplied by publisher] (Source: Journal of Clinical Virology)

Non-compact nucleocapsid protein multimers in influenza-virus-infected cells

Archives of Virology — Wed, 10 Jan 2007 07:54:23 +0100

In this study we demonstrate that, in addition to compact NP oligomers, incompletely folded NP multimers are detected in tracellularly by SDS/PAGE carried out under weak dissociating conditions. In cells infected with avian, human A(H2N2), and human A(H3N2) viruses, NP multimers are detected in the stacking gel of SDS/PAGE as retarded and loose structures dissociating at +50??C. NP multimers are more sensitive to proteolysis than NP oligomers, but they are more resistant to proteolysis than NP monomers. In contrast to compact NP oligomers, NP multimers possess a weak immunoreactivity to some monoclonal antibodies. Pulse-chase experiments have shown that NP multimers appear at early stages of NP synthesis and are partially converted post-translationally into faster-migrating compact NP olig...

Laboratory Exposure to Influenza A H2N2, Germany, 2004–2005, A. Schrauder et al.

Emerging Infectious Diseases Journal — Wed, 15 Nov 2006 10:58:02 +0100

(Source: Emerging Infectious Diseases Journal)

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Characterization of an influenza A H5N2 reassortant as a candidate for live-attenuated and inactivated vaccines against highly pathogenic H5N1 viruses with pandemic potential.

Vaccine — Sat, 21 Oct 2006 08:21:02 +0100

Authors: Desheva JA, Lu XH, Rekstin AR, Rudenko LG, Swayne DE, Cox NJ, Katz JM, Klimov AI 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...

The origins of new pandemic viruses: the acquisition of new host ranges by canine parvovirus and influenza A viruses.

Annual Review of Microbiology — Sat, 01 Jan 2005 05:00:00 +0100

Authors: Parrish CR, Kawaoka Y Transfer of viruses between hosts to create a new self-sustaining epidemic is rare; however, those new viruses can cause severe outbreaks. Examples of such viruses include three pandemic human influenza A viruses and canine parvovirus in dogs. In each case one virus made the original transfer and spread worldwide, and then further adaptation resulted in the emergence of variants worldwide. For the influenza viruses several changes were required for growth and spread between humans, and the emergence of human H2N2 and H3N2 strains in 1957 and 1968 involved the acquisition of three or two new genomic segments, respectively. Adaptation to humans involved several viral genes including the hemagglutinin, the neuraminidase, and the replication proteins. The can...