scholarly journals Mapping the antigenic diversification of SARS-CoV-2

2022 ◽  
Author(s):  
Karlijn van der Straten ◽  
Denise Guerra ◽  
Marit van Gils ◽  
Ilja Bontjer ◽  
Tom G Caniels ◽  
...  
Keyword(s):  
Large Scale ◽  
Seasonal Influenza ◽  
Immune Escape ◽  
Vaccine Effectiveness ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Neutralizing Activity ◽  
Antigenic Cartography ◽  
Vaccination Campaigns

Large-scale vaccination campaigns have prevented countless SARS-CoV-2 infections, hospitalizations and deaths. However, the emergence of variants that escape from immunity challenges the effectiveness of current vaccines. Given this continuing evolution, an important question is when and how to update SARS-CoV-2 vaccines to antigenically match circulating variants, similar to seasonal influenza viruses where antigenic drift necessitates periodic vaccine updates. Here, we studied SARS-CoV-2 antigenic drift by assessing neutralizing activity against variants-of-concern (VOCs) of a unique set of sera from patients infected with a range of VOCs. Infections with ancestral or Alpha strains induced the broadest immunity, while individuals infected with other VOCs had more strain-specific responses. Omicron was substantially resistant to neutralization by sera elicited by all other variants. Antigenic cartography revealed that all VOCs preceding Omicron belong to one antigenic cluster, while Omicron forms a new antigenic cluster associated with immune escape and likely requiring vaccine updates to ensure vaccine effectiveness.

scholarly journals Prediction of influenza vaccine effectiveness for the influenza season 2017/18 in the US

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2067 ◽  
Author(s):  
Slobodan Paessler ◽  
Veljko Veljkovic
Keyword(s):  
Influenza Vaccine ◽  
Seasonal Influenza ◽  
Influenza Season ◽  
Vaccine Effectiveness ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Correct Prediction ◽  
Seasonal Influenza Vaccine ◽  
The Us ◽  
Key Factor

Vaccination against seasonal influenza viruses is the most effective way to prevent infection. A key factor in the effectiveness of the seasonal influenza vaccine is its immunological compatibility with the circulating viruses during the season. The high evolutionary rate, antigenic shift and antigenic drift of influenza viruses, represents the main obstacle for correct prediction of the vaccine effectiveness for an upcoming flu season. Conventional structural and phylogenetic approaches for assessment of vaccine effectiveness have had a limited success in prediction of vaccine efficacy in the past. Recently, a novel bioinformatics approach for assessment of effectiveness of seasonal influenza vaccine was proposed. Here, this approach was used for prediction of the vaccine effectiveness for the influenza season 2017/18 in US.

scholarly journals Molecular Characterization of Seasonal Influenza A and B from Hospitalized Patients in Thailand in 2018–2019

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 977
Author(s):  
Kobporn Boonnak ◽  
Chayasin Mansanguan ◽  
Dennis Schuerch ◽  
Usa Boonyuen ◽  
Hatairat Lerdsamran ◽  
...  
Keyword(s):  
Amino Acid ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Surface Proteins ◽  
Antigenic Drift ◽  
Influenza B ◽  
Receptor Binding Site ◽  
Antigenic Sites ◽  
Ha Protein

Influenza viruses continue to be a major public health threat due to the possible emergence of more virulent influenza virus strains resulting from dynamic changes in virus adaptability, consequent of functional mutations and antigenic drift in surface proteins, especially hemagglutinin (HA) and neuraminidase (NA). In this study, we describe the genetic and evolutionary characteristics of H1N1, H3N2, and influenza B strains detected in severe cases of seasonal influenza in Thailand from 2018 to 2019. We genetically characterized seven A/H1N1 isolates, seven A/H3N2 isolates, and six influenza B isolates. Five of the seven A/H1N1 viruses were found to belong to clade 6B.1 and were antigenically similar to A/Switzerland/3330/2017 (H1N1), whereas two isolates belonged to clade 6B.1A1 and clustered with A/Brisbane/02/2018 (H1N1). Interestingly, we observed additional mutations at antigenic sites (S91R, S181T, T202I) as well as a unique mutation at a receptor binding site (S200P). Three-dimensional (3D) protein structure analysis of hemagglutinin protein reveals that this unique mutation may lead to the altered binding of the HA protein to a sialic acid receptor. A/H3N2 isolates were found to belong to clade 3C.2a2 and 3C.2a1b, clustering with A/Switzerland/8060/2017 (H3N2) and A/South Australia/34/2019 (H3N2), respectively. Amino acid sequence analysis revealed 10 mutations at antigenic sites including T144A/I, T151K, Q213R, S214P, T176K, D69N, Q277R, N137K, N187K, and E78K/G. All influenza B isolates in this study belong to the Victoria lineage. Five out of six isolates belong to clade 1A3-DEL, which relate closely to B/Washington/02/2009, with one isolate lacking the three amino acid deletion on the HA segment at position K162, N163, and D164. In comparison to the B/Colorado/06/2017, which is the representative of influenza B Victoria lineage vaccine strain, these substitutions include G129D, G133R, K136E, and V180R for HA protein. Importantly, the susceptibility to oseltamivir of influenza B isolates, but not A/H1N1 and A/H3N2 isolates, were reduced as assessed by the phenotypic assay. This study demonstrates the importance of monitoring genetic variation in influenza viruses regarding how acquired mutations could be associated with an improved adaptability for efficient transmission.

scholarly journals Global circulation patterns of seasonal influenza viruses vary with antigenic drift

Nature ◽  
2015 ◽  
Vol 523 (7559) ◽  
pp. 217-220 ◽  
Author(s):  
Trevor Bedford ◽  
Steven Riley ◽  
Ian G. Barr ◽  
Shobha Broor ◽  
Mandeep Chadha ◽  
...  
Keyword(s):  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Global Circulation ◽  
Circulation Patterns

scholarly journals Development of an interactive online tool for genome sequence-based influenza vaccine strain selection

2021 ◽  
Author(s):  
◽  
Sweta Pragyan Praharaj
Keyword(s):  
Influenza Vaccine ◽  
Phylogenetic Tree ◽  
Influenza Vaccination ◽  
Vaccine Strain ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
Seasonal Influenza Vaccine ◽  
Antigenic Cartography

Seasonal influenza viruses in humans infect approximately 5 [percent] to 15 [percent] of the population and cause an estimated half-million deaths worldwide per year. Among the four co-circulating seasonal influenza viruses, subtype H3N2 and H1N1 influenza A viruses have rapid mutations and frequent antigenic drift events, leading to frequent updates of vaccine strains in the seasonal influenza vaccine. Seasonal influenza vaccination is the primary option to prevent and control influenza epidemics, and the selection of an antigenic matched vaccine strain is one of the keys to the success of seasonal influenza vaccination. Thus, it is critical to have robust and rapid antigenic analyses of epidemic strains and estimates of their genetic and antigenic relationship with the vaccine strain in use. In this study, we present vaccineEvol, an interactive and user-friendly web visualization tool that allows researchers to comprehend large sequence datasets into antigenic and genetic analyses. With the integration of the genomic sequences from the public database, the tool enables the users to track and analyze both genetic and antigenic evolutionary dynamics of seasonal influenza viruses. Primarily, our application can quantify both genetic and antigenic distances among seasonal H3N2 influenza A viruses and display genetic and antigenic variants using phylogenetic tree and antigenic cartography, respectively. The users can also interactively analyze genetic and antigenic variants between the phylogenetic tree and antigenic cartography. The application performs machine learning based computations in the backend, which was previously developed in our lab, and efficient construction of trees and maps in the frontend. In summary, in this study, an interactive web server was developed for rapid antigenic and genetic analyses of seasonal influenza viruses and thus facilitate seasonal influenza vaccine strain selection.

scholarly journals Preparing intensive care for the next pandemic influenza

Critical Care ◽  
2019 ◽  
Vol 23 (1) ◽  
Author(s):  
Taylor Kain ◽  
Robert Fowler
Keyword(s):  
Resource Allocation ◽  
Influenza Virus ◽  
Intensive Care ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Large Scale ◽  
Influenza Pandemic ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Timely Initiation

Abstract Few viruses have shaped the course of human history more than influenza viruses. A century since the 1918–1919 Spanish influenza pandemic—the largest and deadliest influenza pandemic in recorded history—we have learned much about pandemic influenza and the origins of antigenic drift among influenza A viruses. Despite this knowledge, we remain largely underprepared for when the next major pandemic occurs. While emergency departments are likely to care for the first cases of pandemic influenza, intensive care units (ICUs) will certainly see the sickest and will likely have the most complex issues regarding resource allocation. Intensivists must therefore be prepared for the next pandemic influenza virus. Preparation requires multiple steps, including careful surveillance for new pandemics, a scalable response system to respond to surge capacity, vaccine production mechanisms, coordinated communication strategies, and stream-lined research plans for timely initiation during a pandemic. Conservative models of a large-scale influenza pandemic predict more than 170% utilization of ICU-level resources. When faced with pandemic influenza, ICUs must have a strategy for resource allocation as strain increases on the system. There are several current threats, including avian influenza A(H5N1) and A(H7N9) viruses. As humans continue to live in closer proximity to each other, travel more extensively, and interact with greater numbers of birds and livestock, the risk of emergence of the next pandemic influenza virus mounts. Now is the time to prepare and coordinate local, national, and global efforts.

scholarly journals The 2009 H1N1 Pandemic Influenza Virus: What Next?

mBio ◽  
2010 ◽  
Vol 1 (4) ◽  
Author(s):  
David M. Morens ◽  
Jeffery K. Taubenberger ◽  
Anthony S. Fauci
Keyword(s):  
Influenza Virus ◽  
Immune Escape ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Population Immunity ◽  
Pandemic Virus ◽  
2009 H1n1 ◽  
Immune Escape Mechanisms ◽  
Global Population

ABSTRACT History suggests that the 2009 pandemic H1N1 influenza virus faces extinction unless it mutates to avoid already high global population immunity. The immune escape mechanisms potentially at its disposal include antigenic drift, antigenic shift via genetic reassortment, and intrasubtypic reassortment. Going back to the late 19th century, the evolutionary histories of past pandemic viruses are examined in an effort to better understand the nature and extent of the immune pressures faced by the 2009 pandemic virus in the immediate future. While human influenza viruses have often surprised us, available evidence leads to the hope that the current pandemic virus will continue to cause low or moderate mortality rates if it does not become extinct.

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 Integrating influenza antigenic dynamics with molecular evolution

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Trevor Bedford ◽  
Marc A Suchard ◽  
Philippe Lemey ◽  
Gytis Dudas ◽  
Victoria Gregory ◽  
...  
Keyword(s):  
Molecular Evolution ◽  
Cross Reactivity ◽  
Host Immunity ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Genetic Evolution ◽  
Antigenic Phenotype ◽  
Antigenic Evolution ◽  
Antigenic Cartography ◽  
Virus Strains

Influenza viruses undergo continual antigenic evolution allowing mutant viruses to evade host immunity acquired to previous virus strains. Antigenic phenotype is often assessed through pairwise measurement of cross-reactivity between influenza strains using the hemagglutination inhibition (HI) assay. Here, we extend previous approaches to antigenic cartography, and simultaneously characterize antigenic and genetic evolution by modeling the diffusion of antigenic phenotype over a shared virus phylogeny. Using HI data from influenza lineages A/H3N2, A/H1N1, B/Victoria and B/Yamagata, we determine patterns of antigenic drift across viral lineages, showing that A/H3N2 evolves faster and in a more punctuated fashion than other influenza lineages. We also show that year-to-year antigenic drift appears to drive incidence patterns within each influenza lineage. This work makes possible substantial future advances in investigating the dynamics of influenza and other antigenically-variable pathogens by providing a model that intimately combines molecular and antigenic evolution.

scholarly journals Novel Approaches for The Development of Live Attenuated Influenza Vaccines

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 190 ◽  
Author(s):  
Pilar Blanco-Lobo ◽  
Aitor Nogales ◽  
Laura Rodríguez ◽  
Luis Martínez-Sobrido
Keyword(s):  
Influenza A ◽  
Reverse Genetics ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Influenza Vaccines ◽  
Global Public Health ◽  
Protection Efficacy ◽  
Seasonal Epidemics ◽  
Rapid Generation

Influenza virus still represents a considerable threat to global public health, despite the advances in the development and wide use of influenza vaccines. Vaccination with traditional inactivate influenza vaccines (IIV) or live-attenuated influenza vaccines (LAIV) remains the main strategy in the control of annual seasonal epidemics, but it does not offer protection against new influenza viruses with pandemic potential, those that have shifted. Moreover, the continual antigenic drift of seasonal circulating influenza viruses, causing an antigenic mismatch that requires yearly reformulation of seasonal influenza vaccines, seriously compromises vaccine efficacy. Therefore, the quick optimization of vaccine production for seasonal influenza and the development of new vaccine approaches for pandemic viruses is still a challenge for the prevention of influenza infections. Moreover, recent reports have questioned the effectiveness of the current LAIV because of limited protection, mainly against the influenza A virus (IAV) component of the vaccine. Although the reasons for the poor protection efficacy of the LAIV have not yet been elucidated, researchers are encouraged to develop new vaccination approaches that overcome the limitations that are associated with the current LAIV. The discovery and implementation of plasmid-based reverse genetics has been a key advance in the rapid generation of recombinant attenuated influenza viruses that can be used for the development of new and most effective LAIV. In this review, we provide an update regarding the progress that has been made during the last five years in the development of new LAIV and the innovative ways that are being explored as alternatives to the currently licensed LAIV. The safety, immunogenicity, and protection efficacy profile of these new LAIVs reveal their possible implementation in combating influenza infections. However, efforts by vaccine companies and government agencies will be needed for controlled testing and approving, respectively, these new vaccine methodologies for the control of influenza infections.

scholarly journals Adenoviral Vector-Based Vaccine Platforms for Developing the Next Generation of Influenza Vaccines

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 574 ◽  
Author(s):  
Ekramy E. Sayedahmed ◽  
Ahmed Elkashif ◽  
Marwa Alhashimi ◽  
Suryaprakash Sambhara ◽  
Suresh K. Mittal
Keyword(s):  
Large Scale ◽  
Seasonal Influenza ◽  
Influenza Pandemic ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Vaccine Platform ◽  
Large Numbers ◽  
Universal Influenza Vaccine ◽  
Short Time ◽  
New Strategies

Ever since the discovery of vaccines, many deadly diseases have been contained worldwide, ultimately culminating in the eradication of smallpox and polio, which represented significant medical achievements in human health. However, this does not account for the threat influenza poses on public health. The currently licensed seasonal influenza vaccines primarily confer excellent strain-specific protection. In addition to the seasonal influenza viruses, the emergence and spread of avian influenza pandemic viruses such as H5N1, H7N9, H7N7, and H9N2 to humans have highlighted the urgent need to adopt a new global preparedness for an influenza pandemic. It is vital to explore new strategies for the development of effective vaccines for pandemic and seasonal influenza viruses. The new vaccine approaches should provide durable and broad protection with the capability of large-scale vaccine production within a short time. The adenoviral (Ad) vector-based vaccine platform offers a robust egg-independent production system for manufacturing large numbers of influenza vaccines inexpensively in a short timeframe. In this review, we discuss the progress in the development of Ad vector-based influenza vaccines and their potential in designing a universal influenza vaccine.

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