scholarly journals Influenza viruses resistant to neuraminidase inhibitors.

2014 ◽  
Vol 61 (3) ◽  
Author(s):  
Aneta Nitsch-Osuch ◽  
Lidia Bernadeta Brydak

Neuraminidase inhibitors (NAIs) are antiviral drugs for treatment and prophylaxis of influenza. By blocking the activity of the enzyme neuraminidase, NAIs prevent new viral particles from being released. The increasing use of NAIs brings into focus the risk of drug resistance arising to the class. There are three levels of antiviral resistance according to the way that resistance can be detected or inferred: genotypic, phenotypic and clinical resistance. For many years seasonal influenza viruses resistance to NAIs was low (0.33%). Recently, there has been described an increasing number of resistant seasonal influenza strains to oseltamivir (2% in adults, 5-18% in children). In 2007 there were published data describing 14% resistant to oseltamivir strains of influenza A/H1N1/ in Europe. Approximately 0.5-1.0% of influenza A/H1N1/pdm09 isolates are currently resistant to oseltamivir. The established markers of the resistance to oseltamivir were found in 2.4% of human and 0.8% of avian isolates of influenza A/H5N1/. It has been not observed a cross resistance among oseltamivir and zanamivir. NAIs resistance in influenza viruses is relative and despite its presence patients with resistant viruses may still benefit from receiving these antivirals. The response to treatment with antivirals remains the most important proof of antiviral effectiveness. The rational use of NAIs is essential to preserve the best choice for treatment and prophylaxis of seasonal, avian and pandemic influenza.

2009 ◽  
Vol 14 (38) ◽  
Author(s):  
S Burrel ◽  
L Roncin ◽  
M E Lafon ◽  
H Fleury

The recent emergence of seasonal influenza A(H1N1) strains resistant to oseltamivir makes it necessary to monitoring carefully the susceptibility of human influenza viruses to neuraminidase inhibitors. We report the prevalence of the oseltamivir resistance among influenza A viruses circulating in south-western France over the past three years: seasonal influenza A(H1N1), seasonal influenza A(H3N2), and the influenza A(H1N1)v viruses associated with the ongoing 2009 pandemic. The main result of the study is the absence of oseltamivir resistance in the pandemic H1N1 strains studied so far (n=129).


2010 ◽  
Vol 17 (12) ◽  
pp. 1998-2006 ◽  
Author(s):  
Ali H. Ellebedy ◽  
Thomas P. Fabrizio ◽  
Ghazi Kayali ◽  
Thomas H. Oguin ◽  
Scott A. Brown ◽  
...  

ABSTRACT Human influenza pandemics occur when influenza viruses to which the population has little or no immunity emerge and acquire the ability to achieve human-to-human transmission. In April 2009, cases of a novel H1N1 influenza virus in children in the southwestern United States were reported. It was retrospectively shown that these cases represented the spread of this virus from an ongoing outbreak in Mexico. The emergence of the pandemic led to a number of national vaccination programs. Surprisingly, early human clinical trial data have shown that a single dose of nonadjuvanted pandemic influenza A (H1N1) 2009 monovalent inactivated vaccine (pMIV) has led to a seroprotective response in a majority of individuals, despite earlier studies showing a lack of cross-reactivity between seasonal and pandemic H1N1 viruses. Here we show that previous exposure to a contemporary seasonal H1N1 influenza virus and to a lesser degree a seasonal influenza virus trivalent inactivated vaccine is able to prime for a higher antibody response after a subsequent dose of pMIV in ferrets. The more protective response was partially dependent on the presence of CD8+ cells. Two doses of pMIV were also able to induce a detectable antibody response that provided protection from subsequent challenge. These data show that previous infection with seasonal H1N1 influenza viruses likely explains the requirement for only a single dose of pMIV in adults and that vaccination campaigns with the current pandemic influenza vaccines should reduce viral burden and disease severity in humans.


2021 ◽  
Vol 12 ◽  
Author(s):  
Laura Sánchez-de Prada ◽  
Raúl Ortiz de Lejarazu-Leonardo ◽  
Javier Castrodeza-Sanz ◽  
Eduardo Tamayo-Gómez ◽  
José María Eiros-Bouza ◽  
...  

BackgroundSex differences in immune responses are well known. However, the humoral response in males and females in the case of influenza vaccination is yet to be characterized since studies have shown uneven results.MethodsA retrospective study was conducted in 2,243 individuals (46.9% males) divided by age (15–64 and ≥65 years old). A serological analysis was performed by hemagglutination inhibition assay (HI) just before and 28 days after annual vaccination against seasonal influenza viruses in people vaccinated during the 2006–2018 seasons. A comparison of the humoral responses against influenza A and B viruses contained in the vaccine, between male and female individuals in young adults and elderly was conducted.ResultsSignificative higher humoral response against classical influenza A (H1N1), A(H1N1)pdm09 subtype and B/Victoria lineage in terms of seroconversion rate were found in elderly women. No significant differences were found in the case of A(H3N2) subtype.ConclusionsElderly women seem to display a greater humoral response against classical A(H1N1), pandemic A(H1N1)pmd09 and B/Victoria lineage than elderly men. Sex dimorphism does not affect young adults.


2009 ◽  
Vol 14 (32) ◽  
Author(s):  
H Uphoff ◽  
S Geis ◽  
A Grüber ◽  
A M Hauri

For the next influenza season (winter 2009-10) the relative contributions to virus circulation and influenza-associated morbidity of the seasonal influenza viruses A(H3N2), A(H1N1) and B, and the new influenza A(H1N1)v are still unknown. We estimated the chances of seasonal influenza to circulate during the upcoming season using data of the German influenza sentinel scheme from 1992 to 2009. We calculated type and subtype-specific indices for past exposure and the corresponding morbidity indices for each season. For the upcoming season 2009-10 our model suggests that it is unlikely that influenza A(H3N2) will circulate with more than a low intensity, seasonal A(H1N1) with more than a low to moderate intensity, and influenza B with more than a low to median intensity. The probability of a competitive circulation of seasonal influenza A with the new A(H1N1)v is low, increasing the chance for the latter to dominate the next influenza season in Germany.


2014 ◽  
Vol 19 (1) ◽  
Author(s):  
E Takashita ◽  
M Ejima ◽  
R Itoh ◽  
M Miura ◽  
A Ohnishi ◽  
...  

Six influenza A(H1N1)pdm09 viruses were detected in Sapporo, Japan, between November and December 2013. All six viruses possessed an H275Y substitution in the neuraminidase protein, which confers cross-resistance to oseltamivir and peramivir. No epidemiological link among the six cases could be identified; none of them had received neuraminidase inhibitors before specimen collection. The haemagglutinin and neuraminidase genes of the six viruses were closely related to one another, suggesting clonal spread of a single resistant virus.


Author(s):  
Merryn Roe ◽  
Matthew Kaye ◽  
Pina Iannello ◽  
Hilda Lau ◽  
Iwona Buettner ◽  
...  

As part of its role in the World Health Organization’s (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne received a record total of 5866 human influenza positive samples during 2017. Viruses were analysed for their antigenic, genetic and antiviral susceptibility properties and were propagated in qualified cells and hens’ eggs for use as potential seasonal influenza vaccine virus candidates. In 2017, influenza A(H3) viruses predominated over influenza A(H1)pdm09 and B viruses, accounting for a total of 54% of all viruses analysed. The majority of A(H1)pdm09, A(H3) and influenza B viruses analysed at the Centre were found to be antigenically similar to the respective WHO recommended vaccine strains for the Southern Hemisphere in 2017. However, phylogenetic analysis indicated that the majority of circulating A(H3) viruses had undergone genetic drift relative to the WHO recommended vaccine strain for 2017. Of 3733 samples tested for susceptibility to the neuraminidase inhibitors oseltamivir and zanamivir, only two A(H1)pdm09 viruses and one A(H3) virus showed highly reduced inhibition by oseltamivir, while just one A(H1)pdm09 virus showed highly reduced inhibition by zanamivir.


2021 ◽  
Author(s):  
Ryan R Chaparian ◽  
Alfred T Harding ◽  
Kristina Riebe ◽  
Amelia Karlsson ◽  
Gregory D Sempowski ◽  
...  

Vaccines targeting SARS-CoV-2 have gained emergency FDA approval, however the breadth against emerging variants and the longevity of protection remains unknown. Post-immunization boosting may be required, perhaps on an annual basis if the virus becomes an endemic pathogen. Seasonal influenza virus vaccines are already developed every year, an undertaking made possible by a robust global vaccine production and distribution infrastructure. To create a seasonal combination vaccine targeting influenza viruses and SARS-CoV-2 that is also amenable to frequent reformulation, we have developed a recombinant influenza A virus (IAV) genetic platform that reprograms the virus to package an immunogenic domain of the SARS-CoV-2 spike (S) protein onto IAV particles. Vaccination with this combination vaccine elicits neutralizing antibodies and provides protection from lethal challenge with both pathogens. This technology may allow for leveraging of established influenza vaccine infrastructure to generate a cost-effective and scalable seasonal vaccine solution for both influenza and coronaviruses.


2009 ◽  
Vol 83 (20) ◽  
pp. 10366-10373 ◽  
Author(s):  
Aeron C. Hurt ◽  
Jessica K. Holien ◽  
Michael Parker ◽  
Anne Kelso ◽  
Ian G. Barr

ABSTRACT The neuraminidase inhibitors zanamivir and oseltamivir are marketed for the treatment and prophylaxis of influenza and have been stockpiled by many countries for use in a pandemic. Although recent surveillance has identified a striking increase in the frequency of oseltamivir-resistant seasonal influenza A (H1N1) viruses in Europe, the United States, Oceania, and South Africa, to date there have been no reports of significant zanamivir resistance among influenza A (H1N1) viruses or any other human influenza viruses. We investigated the frequency of oseltamivir and zanamivir resistance in circulating seasonal influenza A (H1N1) viruses in Australasia and Southeast Asia. Analysis of 391 influenza A (H1N1) viruses isolated between 2006 and early 2008 from Australasia and Southeast Asia revealed nine viruses (2.3%) that demonstrated markedly reduced zanamivir susceptibility and contained a previously undescribed Gln136Lys (Q136K) neuraminidase mutation. The mutation had no effect on oseltamivir susceptibility but caused approximately a 300-fold and a 70-fold reduction in zanamivir and peramivir susceptibility, respectively. The role of the Q136K mutation in conferring zanamivir resistance was confirmed using reverse genetics. Interestingly, the mutation was not detected in the primary clinical specimens from which these mutant isolates were grown, suggesting that the resistant viruses either occurred in very low proportions in the primary clinical specimens or arose during MDCK cell culture passage. Compared to susceptible influenza A (H1N1) viruses, the Q136K mutant strains displayed greater viral fitness than the wild-type virus in MDCK cells but equivalent infectivity and transmissibility in a ferret model.


2015 ◽  
Vol 23 (1) ◽  
Author(s):  
Daniela Pitigoi ◽  
George Necula ◽  
Viorel Alexandrescu ◽  
Maria Elena Mihai ◽  
Carmen Maria Cherciu ◽  
...  

AbstractBackgound. Using influenza epidemiological and virological surveillance data, we aimed at investigating the profile of influenza viruses circulating in Romania during the season 2012-2013 and estimating the effectiveness (VE) of the seasonal vaccine. Methods. We tested all specimens collected from patients with influenza like illness (ILI) in the national surveillance system between week 40/2012 to week 20/2013. Influenza A/B positive specimens identified by molecular detection (RT-PCR) were further characterized. We used hemagglutination inhibition assay for antigenic characterization and chemiluminiscence assay for the antiviral susceptibility testing. Subsequently we conducted nucleotide sequencing of hemagglutinin and neuraminidase genes and phylogenetic tree analyses. We estimated influenza VE using the test negative case-control study design, as 1-odds ratio of vaccination among ILI cases positive for influenza and ILI negative controls. Results and Discussions. We tested 1087 specimens, and 537 cases were positive (56.2% influenza B, 40.6% A(H1N1)pdm09, 3.2% A(H3N2). Sixty-four influenza viruses were antigenically and/or genetically characterized. A(H1N1)pdm09 viruses were related to the vaccine strain A/ California/07/2009 and clustered with genetic group 6 similar to A/St. Petersburg/27/2011. Influenza B viruses belonged to clade 2 of type B/Yamagata lineage, related to B/Estonia/55669/2011 except one, B/Victoria lineage, representative strain B/Brisbane/60/2008. A(H3) viruses clustered with group 3C of the A/Victoria/208/2009 clade, similar to the vaccine strain A/Victoria/361/2011. All tested strains (57) demonstrated susceptibility to oseltamivir and zanamivir. The adjusted seasonal influenza vaccine effectiveness against influenza A(H1N1)pdm09 (N=119) was 76.9% (95% CI: -113.4, 98.5), suggesting a good protection, consistent with the good match between the vaccine and circulating strains.


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