scholarly journals Lessons From Influenza Pandemics of the Last 100 Years

2019 ◽  
Author(s):  
Arnold S Monto ◽  
Keiji Fukuda
Keyword(s):  
Avian Influenza ◽  
Seasonal Influenza ◽  
Influenza Pandemic ◽  
Risk Groups ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
Influenza Pandemics ◽  
Fundamental Difficulty ◽  
1918 Influenza ◽  
The Impact

Abstract Seasonal influenza is an annual occurrence, but it is the threat of pandemics that produces universal concern. Recurring reports of avian influenza viruses severely affecting humans have served as constant reminders of the potential for another pandemic. Review of features of the 1918 influenza pandemic and subsequent ones helps in identifying areas where attention in planning is critical. Key among such issues are likely risk groups and which interventions to employ. Past pandemics have repeatedly underscored, for example, the vulnerability of groups such as pregnant women and taught other lessons valuable for future preparedness. While a fundamental difficulty in planning for the next pandemic remains their unpredictability and infrequency, this uncertainty can be mitigated, in part, by optimizing the handling of the much more predictable occurrence of seasonal influenza. Improvements in antivirals and novel vaccine formulations are critical in lessening the impact of both pandemic and seasonal influenza.

scholarly journals Immune Escape Variants of H9N2 Influenza Viruses Containing Deletions at the Hemagglutinin Receptor Binding Site Retain Fitness In Vivo and Display Enhanced Zoonotic Characteristics

2017 ◽  
Vol 91 (14) ◽  
Author(s):  
Thomas P. Peacock ◽  
Donald J. Benton ◽  
Joe James ◽  
Jean-Remy Sadeyen ◽  
Pengxiang Chang ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Receptor Binding ◽  
Immune Escape ◽  
Influenza Pandemic ◽  
Influenza Viruses ◽  
Viral Fitness ◽  
Antigenic Drift ◽  
Zoonotic Infection ◽  
Avian Influenza Viruses ◽  
The Impact

ABSTRACT H9N2 avian influenza viruses are enzootic in poultry across Asia and North Africa, where they pose a threat to human health as both zoonotic agents and potential pandemic candidates. Poultry vaccination against H9N2 viruses has been employed in many regions; however, vaccine effectiveness is frequently compromised due to antigenic drift arising from amino acid substitutions in the major influenza virus antigen hemagglutinin (HA). Using selection with HA-specific monoclonal antibodies, we previously identified H9N2 antibody escape mutants that contained deletions of amino acids in the 220 loop of the HA receptor binding sites (RBSs). Here we analyzed the impact of these deletions on virus zoonotic infection characteristics and fitness. We demonstrated that mutant viruses with RBS deletions are able to escape polyclonal antiserum binding and are able to infect and be transmitted between chickens. We showed that the deletion mutants have increased binding to human-like receptors and greater replication in primary human airway cells; however, the mutant HAs also displayed reduced pH and thermal stability. In summary, we infer that variant influenza viruses with deletions in the 220 loop could arise in the field due to immune selection pressure; however, due to reduced HA stability, we conclude that these viruses are unlikely to be transmitted from human to human by the airborne route, a prerequisite for pandemic emergence. Our findings underscore the complex interplay between antigenic drift and viral fitness for avian influenza viruses as well as the challenges of predicting which viral variants may pose the greatest threats for zoonotic and pandemic emergence. IMPORTANCE Avian influenza viruses, such as H9N2, cause disease in poultry as well as occasionally infecting humans and are therefore considered viruses with pandemic potential. Many countries have introduced vaccination of poultry to try to control the disease burden; however, influenza viruses are able to rapidly evolve to escape immune pressure in a process known as “antigenic drift.” Previously, we experimentally generated antigenic-drift variants in the laboratory, and here, we test our “drifted” viruses to assess their zoonotic infection characteristics and transmissibility in chickens. We found that the drifted viruses were able to infect and be transmitted between chickens and showed increased binding to human-like receptors. However, the drift mutant viruses displayed reduced stability, and we predict that they are unlikely to be transmitted from human to human and cause an influenza pandemic. These results demonstrate the complex relationship between antigenic drift and the potential of avian influenza viruses to infect humans.

scholarly journals Avian Influenza & Human Health

2014 ◽  
Vol 5 (1) ◽  
pp. 35-38
Author(s):  
Prosun Roy ◽  
SM Rashed-ul Islam ◽  
Farhana Rahman ◽  
Md Mahmudur Rahman Siddiqui
Keyword(s):  
Avian Influenza ◽  
Human Health ◽  
Viral Infections ◽  
Influenza Pandemic ◽  
Animal Health ◽  
Genetic Mutation ◽  
Influenza Viruses ◽  
Avian Influenza Viruses ◽  
Influenza Pandemics ◽  
The World

The world is now under human pandemic threat by avian influenza viruses. As the human, animal and the environment interact closely from the dawn of the civilization, human health is tremendously influenced by animal health and their health issues. In last few centuries the world has suffered a number of influenza pandemics killing millions of people such as Spanish Flu (1918), Asiatic or Russian Flu (1889-1890), Asian Flu (1957-1958) etc. The exceptional capability of genetic mutation of the influenza viruses offered threats to the whole world time to time. Like all other countries Bangladesh also not away from the heat of the situation. Human cases of avian influenza subtype H1N1, H3, H5N1, and H9N2 have already been reported from Bangladesh. This article reviews the information available on pandemic potential of avian influenza viruses. The article also sheds light on different avian influenza viruses along with some emphasis on clinical and preventive aspects of the avian influenza viral infections, and on avian influenza pandemic preparedness of Bangladesh. DOI: http://dx.doi.org/10.3329/akmmcj.v5i1.18839 Anwer Khan Modern Medical College Journal Vol. 5, No. 1: January 2014, Pages 35-38

scholarly journals Novel Highly Pathogenic Avian A(H5N2) and A(H5N8) Influenza Viruses of Clade 2.3.4.4 from North America Have Limited Capacity for Replication and Transmission in Mammals

mSphere ◽  
2016 ◽  
Vol 1 (2) ◽  
Author(s):  
Bryan S. Kaplan ◽  
Marion Russier ◽  
Trushar Jeevan ◽  
Bindumadhav Marathe ◽  
Elena A. Govorkova ◽  
...  
Keyword(s):  
North America ◽  
Avian Influenza ◽  
North American ◽  
Influenza Viruses ◽  
Morbidity And Mortality ◽  
Avian Influenza Viruses ◽  
Highly Pathogenic ◽  
The North ◽  
Domestic Poultry ◽  
The Impact

ABSTRACT Highly pathogenic H5 influenza viruses have been introduced into North America from Asia, causing extensive morbidity and mortality in domestic poultry. The introduced viruses have reassorted with North American avian influenza viruses, generating viral genotypes not seen on other continents. The experiments and analyses presented here were designed to assess the impact of this genetic diversification on viral phenotypes, particularly as regards mammalian hosts, by comparing the North American viruses with their Eurasian precursor viruses. Highly pathogenic influenza A(H5N8) viruses from clade 2.3.4.4 were introduced to North America by migratory birds in the fall of 2014. Reassortment of A(H5N8) viruses with avian viruses of North American lineage resulted in the generation of novel A(H5N2) viruses with novel genotypes. Through sequencing of recent avian influenza viruses, we identified PB1 and NP gene segments very similar to those in the viruses isolated from North American waterfowl prior to the introduction of A(H5N8) to North America, highlighting these bird species in the origin of reassortant A(H5N2) viruses. While they were highly virulent and transmissible in poultry, we found A(H5N2) viruses to be low pathogenic in mice and ferrets, and replication was limited in both hosts compared with those of recent highly pathogenic avian influenza (HPAI) H5N1 viruses. Molecular characterization of the hemagglutinin protein from A(H5N2) viruses showed that the receptor binding preference, cleavage, and pH of activation were highly adapted for replication in avian species and similar to those of other 2.3.4.4 viruses. In addition, North American and Eurasian clade 2.3.4.4 H5NX viruses replicated to significantly lower titers in differentiated normal human bronchial epithelial cells than did seasonal human A(H1N1) and highly pathogenic A(H5N1) viruses isolated from a human case. Thus, despite their having a high impact on poultry, our findings suggest that the recently emerging North American A(H5N2) viruses are not expected to pose a substantial threat to humans and other mammals without further reassortment and/or adaptation and that reassortment with North American viruses has not had a major impact on viral phenotype. IMPORTANCE Highly pathogenic H5 influenza viruses have been introduced into North America from Asia, causing extensive morbidity and mortality in domestic poultry. The introduced viruses have reassorted with North American avian influenza viruses, generating viral genotypes not seen on other continents. The experiments and analyses presented here were designed to assess the impact of this genetic diversification on viral phenotypes, particularly as regards mammalian hosts, by comparing the North American viruses with their Eurasian precursor viruses.

scholarly journals Generation of Live Attenuated Influenza Virus by Using Codon Usage Bias

2015 ◽  
Vol 89 (21) ◽  
pp. 10762-10773 ◽  
Author(s):  
Rebecca L. Y. Fan ◽  
Sophie A. Valkenburg ◽  
Chloe K. S. Wong ◽  
Olive T. W. Li ◽  
John M. Nicholls ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Codon Usage ◽  
Codon Bias ◽  
Seasonal Influenza ◽  
Viral Proteins ◽  
Influenza Viruses ◽  
Donor Strain ◽  
Avian Influenza Viruses ◽  
Attenuated Viruses

ABSTRACTSeasonal influenza epidemics and occasional pandemics threaten public health worldwide. New alternative strategies for generating recombinant viruses with vaccine potential are needed. Interestingly, influenza viruses circulating in different hosts have been found to have distinct codon usage patterns, which may reflect host adaptation. We therefore hypothesized that it is possible to make a human seasonal influenza virus that is specifically attenuated in human cells but not in eggs by converting its codon usage so that it is similar to that observed from avian influenza viruses. This approach might help to generate human live attenuated viruses without affecting their yield in eggs. To test this hypothesis, over 300 silent mutations were introduced into the genome of a seasonal H1N1 influenza virus. The resultant mutant was significantly attenuated in mammalian cells and mice, yet it grew well in embryonated eggs. A single dose of intranasal vaccination induced potent innate, humoral, and cellular immune responses, and the mutant could protect mice against homologous and heterologous viral challenges. The attenuated mutant could also be used as a vaccine master donor strain by introducing hemagglutinin and neuraminidase genes derived from other strains. Thus, our approach is a successful strategy to generate attenuated viruses for future application as vaccines.IMPORTANCEVaccination has been one of the best protective measures in combating influenza virus infection. Current licensed influenza vaccines and their production have various limitations. Our virus attenuation strategy makes use of the codon usage biases of human and avian influenza viruses to generate a human-derived influenza virus that is attenuated in mammalian hosts. This method, however, does not affect virus replication in eggs. This makes the resultant mutants highly compatible with existing egg-based vaccine production pipelines. The viral proteins generated from the codon bias mutants are identical to the wild-type viral proteins. In addition, our massive genome-wide mutational approach further minimizes the concern over reverse mutations. The potential use of this kind of codon bias mutant as a master donor strain to generate other live attenuated viruses is also demonstrated. These findings put forward a promising live attenuated influenza vaccine generation strategy to control influenza.

scholarly journals Development and Evaluation of Vero Cell-Derived Master Donor Viruses for Influenza Pandemic Preparedness

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 626
Author(s):  
Po-Ling Chen ◽  
Tsai-Teng Tzeng ◽  
Alan Yung-Chih Hu ◽  
Lily Hui-Ching Wang ◽  
Min-Shi Lee
Keyword(s):  
Vero Cell ◽  
Seasonal Influenza ◽  
Influenza Pandemic ◽  
High Growth ◽  
Vero Cells ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Pandemic Preparedness ◽  
Influenza Pandemics ◽  
Production Platform

The embryonated egg-based platform currently produces the majority of seasonal influenza vaccines by employing a well-developed master donor virus (MDV, A/PR/8/34 (PR8)) to generate high-growth reassortants (HGRs) for A/H1N1 and A/H3N2 subtypes. Although the egg-based platform can supply enough seasonal influenza vaccines, it cannot meet surging demands during influenza pandemics. Therefore, multi-purpose platforms are desirable for pandemic preparedness. The Vero cell-based production platform is widely used for human vaccines and could be a potential multi-purpose platform for pandemic influenza vaccines. However, many wild-type and egg-derived influenza viruses cannot grow efficiently in Vero cells. Therefore, it is critical to develop Vero cell-derived high-growth MDVs for pandemic preparedness. In this study, we evaluated two in-house MDVs (Vero-15 and VB5) and two external MDVs (PR8 and PR8-HY) to generate Vero cell-derived HGRs for five avian influenza viruses (AIVs) with pandemic potentials (H5N1 clade 2.3.4, H5N1 clade 2.3.2.1, American-lineage H5N2, H7N9 first wave and H7N9 fifth wave). Overall, no single MDV could generate HGRs for all five AIVs, but this goal could be achieved by employing two in-house MDVs (vB5 and Vero-15). In immunization studies, mice received two doses of Vero cell-derived inactivated H5N1 and H7N9 whole virus antigens adjuvanted with alum and developed robust antibody responses.

scholarly journals The Impact of Migratory Flyways on the Spread of Avian Influenza Virus in North America

2016 ◽  
Author(s):  
Mathieu Fourment ◽  
Aaron E. Darling ◽  
Edward C. Holmes
Keyword(s):  
Influenza Virus ◽  
Genetic Structure ◽  
North America ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Bird Species ◽  
Influenza Viruses ◽  
Data Sets ◽  
Avian Influenza Viruses ◽  
The Impact

AbstractWild birds are the major reservoir hosts for influenza A viruses (AIVs) and have been implicated in the emergence of pandemic events in livestock and human populations. Understanding how AIVs spread within and across continents is therefore critical to the development of successful strategies to manage and reduce the impact of influenza outbreaks. In North America many bird species undergo seasonal migratory movements along a North-South axis, thereby fostering opportunities for viruses to spread over long distances. However, the role played by such avian flyways in shaping the genetic structure of AIV populations has proven controversial. To assess the relative contribution of bird migration along flyways to the genetic structure of AIV we performed a large-scale phylogeographic study of viruses sampled in the USA and Canada, involving the analysis of 3805 to 4505 sequences from 36 to 38 geographic localities depending on the gene data set. To assist this we developed a maximum likelihood-based genetic algorithm to explore a wide range of complex spatial models, thereby depicting a more complete picture of the migration network than previous studies. Based on phylogenies estimated from nucleotide data sets, our results show that AIV migration rates within flyways are significantly higher than those between flyways, indicating that the migratory patterns of birds play a key role in pathogen dispersal. These findings provide valuable insights into the evolution, maintenance and transmission of AIVs, in turn allowing the development of improved programs for surveillance and risk assessment.Significance StatementAvian influenza viruses infect a wide variety of wild bird species and represent a potential disease threat to the poultry industry and hence to human and livestock populations. However, the ecological factors that drive the geographic spread and evolution of these viruses are both poorly understood and controversial at the continental scale, particularly the role played by migratory flyways in shaping patterns of virus dispersal. Using a novel phylogeographic analysis of large genomic data sets we show migration flyways act as important transmission barriers to the spread of avian influenza viruses in North America. Hence, these results indicate that the spread of avian influenza virus in wild birds in North America has an element of predictability.

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