Rational selection of hemagglutinin variants of H3N2 influenza viruses in preparation of live influenza vaccine strains to optimize growth characteristics

2021 ◽  
Vol 21 (3) ◽  
pp. 141-146
Author(s):  
Ekaterina A. Stepanova ◽  
Ekaterina A. Bazhenova ◽  
Elena V. Krutikova ◽  
Nataliya V. Larionova ◽  
Irina V. Kiseleva ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Vaccine Strain ◽  
Correct Choice ◽  
Growth Characteristics ◽  
Influenza Viruses ◽  
Human Respiratory Tract ◽  
Chicken Embryos ◽  
Epidemic Season ◽  
Hemagglutination Inhibition Test ◽  
Antigenic Properties

BACKGROUND: Up to date Russian live attenuated influenza vaccines are produced in developing chicken embryos. During passaging in embryos, the virus isolated from the human respiratory tract undergoes adaptation to the receptors in embryos. The population of the virus, at any passage in chicken embryos, is heterogeneous and contains variants of viruses with one or another set of adaptive substitutions. Before preparing the vaccine strain, the population of the epidemic virus is cloned and the genetic sequence of the hemagglutinin and neuraminidase clones is analyzed. The growth characteristics of the vaccine strain and its antigenic properties depend on the correct choice of the variant of the virus. AIM: The aim of the study was to select the variant of the H3N2 subtype virus for the preparation of a vaccine reassortant based on data on the composition of the population and an assessment of its growth properties. MATERIALS AND METHODS: Viruses were cloned in developing chicken embryos, sequencing of the hemagglutinin and neuraminidase genes of the clones was performed. On the basis of the clones selected based on the results of the analysis of the population, strains of a live influenza vaccine were obtained by the reassortment in the chicken embryos. The growth characteristics of the strains, the phenotype in eggs, and the antigenic properties by hemagglutination inhibition test were evaluated. RESULTS: The influenza virus A/Kansas/14/2017 recommended by WHO for the epidemic season 2019-2020 acquired a pair of D190N + N246T substitutions dominating in the population at the 7th passage in eggs. From the population of A/Kansas/14/2017-like strain A/Brisbane/34/2018, from the third passage in the eggs, it was possible to obtain a variant of the virus with substitutions G186V + S219Y in hemagglutinin. The growth characteristics of the strain based on A/Kansas/14/2017 (passage E7) were significantly inferior to the characteristics of the strain based on A/Brisbane/34/2018 (passage E3), in the absence of differences in antigenic properties. CONCLUSIONS: The variant of egg adaptation of hemagglutinin G186V in strains of clade 3c.3a is preferable for the preparation of live influenza vaccine strains; variant N246T is not optimal. When preparing strains, it is necessary to analyze the composition of the virus population by cloning and choose the most optimal option for preparing strains. The persistence of egg-adaptive substitutions in passaged variants of the virus is not always optimal for strains of live influenza vaccine, and therefore it is preferable to use the population as close as possible to the initial variant to start work on the strain.

scholarly journals Using Sequence Data To Infer the Antigenicity of Influenza Virus

mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
Hailiang Sun ◽  
Jialiang Yang ◽  
Tong Zhang ◽  
Li-Ping Long ◽  
Kun Jia ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza Vaccine ◽  
Vaccine Strain ◽  
Sequence Data ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Computational Method ◽  
Vaccination Programs ◽  
Antigenic Properties ◽  
Human Labor

ABSTRACTThe efficacy of current influenza vaccines requires a close antigenic match between circulating and vaccine strains. As such, timely identification of emerging influenza virus antigenic variants is central to the success of influenza vaccination programs. Empirical methods to determine influenza virus antigenic properties are time-consuming and mid-throughput and require live viruses. Here, we present a novel, experimentally validated, computational method for determining influenza virus antigenicity on the basis of hemagglutinin (HA) sequence. This method integrates a bootstrapped ridge regression with antigenic mapping to quantify antigenic distances by using influenza HA1 sequences. Our method was applied to H3N2 seasonal influenza viruses and identified the 13 previously recognized H3N2 antigenic clusters and the antigenic drift event of 2009 that led to a change of the H3N2 vaccine strain.IMPORTANCEThis report supplies a novel method for quantifying antigenic distance and identifying antigenic variants using sequences alone. This method will be useful in influenza vaccine strain selection by significantly reducing the human labor efforts for serological characterization and will increase the likelihood of correct influenza vaccine candidate selection.

scholarly journals Hemagglutination inhibition antibody titers as a correlate of protection against influenza disease in the 2018/2019 epidemic season in Poland

2020 ◽  
Author(s):  
Ewelina Hallmann-Szelińska ◽  
Karol Szymański ◽  
Katarzyna Łuniewska ◽  
Katarzyna Kondratiuk ◽  
Lidia Bernadeta Brydak
Keyword(s):  
Hemagglutination Inhibition ◽  
Influenza A ◽  
Age Groups ◽  
Influenza Viruses ◽  
Clinical Samples ◽  
Influenza B Virus ◽  
Influenza B ◽  
Epidemic Season ◽  
Hemagglutination Inhibition Test ◽  
Inhibition Antibody

The aim of this study was to determine the level of antibodies against hemagglutinin of influenza viruses in the sera of people in the seven age groups in the epidemic season 2018/2019 in Poland. The level of anti-hemagglutinin antibodies was determined by hemagglutination inhibition test (HAI). 1050 clinical samples from all over the country were tested. The level of antibodies against influenza viruses was highest in the 10–14 age group for A/Singapore/INFIMH-16-0019/2016 (H3N2) and B/Phuket/3073/2013 Yamagata lineage antigens. These results confirm the circulation of four antigenically different influenza virus strains, two subtypes of influenza A virus – A/Michigan/45/2015 (H1N1)pdm09 and A/Singapore/INFIMH-16-0019/2016 (H3N2) and two lineages of influenza B virus – B/Colorado/06/2017 – Victoria lineage and B/Phuket/3073/2013 Yamagata lineage.

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.

Growth characteristics of experimental live influenza vaccine strains with modified NP and NS genes

2021 ◽  
Vol 21 (3) ◽  
pp. 135-139
Author(s):  
Polina I. Prokopenko ◽  
Виктория A. Matyushenko ◽  
Irina N. Isakova-Sivak ◽  
Larisa G. Rudenko
Keyword(s):  
Influenza Vaccine ◽  
Respiratory Tract ◽  
Growth Characteristics ◽  
Influenza Viruses ◽  
Full Length ◽  
Open Reading Frame ◽  
Ns1 Protein ◽  
Reading Frame ◽  
Ns1 Gene ◽  
Np Gene

BACKGROUND: Vaccination is the most effective means of fighting influenza epidemics, but the immunogenicity of licensed influenza vaccines is not always satisfactory. One of the ways to increase the immunogenicity of an attenuated live influenza vaccine is to shorten the open reading frame of the NS1 protein, a modulator of innate antiviral immunity. In addition, the T-cell response to vaccination can be optimized by including the NP gene from the epidemic parental virus into the genome of vaccine strains. MATERIALS AND METHODS: The open reading frame of the NS1 protein of the master donor virus A/Leningrad/134/17/57 was truncated to 126 amino acids by site-directed mutagenesis. The HA, NA, and NP genes of the model virus A/Anhui/1/2013 (H7N9) were cloned into the pCIPolISapIT vector. The rescue of recombinant influenza viruses was performed by transfection of Vero cells with a desired set of plasmids. The growth properties of the recombinant viruses were determined in embryonated chicken eggs incubated at different temperatures, as well as in the tissues of the respiratory tract of mice (nasal turbinates, lungs). RESULTS: Experimental live influenza vaccine strains of subtype H7N9 with genome compositions 6:2 and 5:3 and carrying a full-length or truncated NS1 gene were actively replicated in eggs under optimal conditions, while maintaining the temperature-sensitive and cold-adapted phenotypes characteristic of classical live influenza vaccine strains. All viruses lacked the ability to grow in the lungs of C57BL/6J mice, which confirms the attenuated phenotype of the viruses. In the nasal passages of mice, only viruses with the full-length NS1 gene replicated, while viruses expressing the truncated NS1 protein were not detected in the respiratory tract of animals. CONCLUSIONS: The results indicate that modification of the NS1 gene of the vaccine virus and the inclusion of wild-type NP gene in its genome does not affect its growth characteristics in eggs. A decrease in the activity of viral replication in the upper respiratory tract of mice with a shortening of the NS1 open reading frame indicates an increase in the attenuating properties of modified vaccines, which opens up prospects for the use of new vaccines in children under three years of age.

Adju-fluax

1974 ◽  
Vol 12 (20) ◽  
pp. 79-80
Keyword(s):  
Influenza Vaccine ◽  
Vaccine Strain ◽  
Antibody Formation ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Degree Of Protection ◽  
New Type

Adju-fluax (MSD) is a new type of killed influenza vaccine for injection. Like all influenza vaccines, it is maximally effective only as long as the virus from which it was prepared is antigenically similar to that circulating in the population. Because the current influenza viruses, both A and B, are undergoing antigenic change, it is difficult to predict what kind of virus will be important next winter. Assuming the new strain is related antigenically to the vaccine strain, Adju-fluax has an important advantage over other vaccines because it contains an adjuvant - a substance which markedly potentiates antibody formation. Adjuvants increase both the degree of protection and its duration.1 2

scholarly journals Circulating influenza viruses and the effectiveness of seasonal influenza vaccine in Romania, season 2012-2013 / Virusurile gripale circulante și eficacitatea vaccinului gripal sezonier în România, în sezonul 2012-2013

2015 ◽  
Vol 23 (1) ◽  
Author(s):  
Daniela Pitigoi ◽  
George Necula ◽  
Viorel Alexandrescu ◽  
Maria Elena Mihai ◽  
Carmen Maria Cherciu ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Vaccine Strain ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Nucleotide Sequencing ◽  
Influenza B ◽  
Seasonal Influenza Vaccine ◽  
Negative Case ◽  
Influenza A H1n1

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.

Influenza vaccine strain selection and recent studies on the global migration of seasonal influenza viruses

Vaccine ◽  
2008 ◽  
Vol 26 ◽  
pp. D31-D34 ◽  
Author(s):  
Colin A. Russell ◽  
Terry C. Jones ◽  
Ian G. Barr ◽  
Nancy J. Cox ◽  
Rebecca J. Garten ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Vaccine Strain ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Strain Selection ◽  
Global Migration

scholarly journals A31 Diversity change of influenza A (H3N2) strains circulating in Brazil during 2017–8: What to expect in the coming winter?

2019 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
P C Resende ◽  
B Caetano ◽  
A Matos ◽  
J Lopes ◽  
C Garcia ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Vaccine Strain ◽  
Influenza A ◽  
Phylogenetic Reconstruction ◽  
Distinct Group ◽  
Genetic Profile ◽  
Epidemic Season ◽  
Epidemic Period ◽  
Trivalent Vaccine ◽  
Universal Influenza Vaccine

Abstract The H3N2 subtype of influenza A (H3N2) was the predominant strain during the early months of the 2017 influenza epidemic in Brazil. In Australia, it was responsible for a strong and prolonged 2017 season and reached the Northern hemisphere causing an intense 2017/8 influenza season. Several genetic and antigenic A(H3N2) variants were circulating, which made the decision about which strain to incorporate into the influenza vaccine challenging. For 2018, the WHO selected a new H3N2 strain, A/Singapore/INFIMH-16-0019/2016-like, to replace the strain A/HongKong/4801/2014-like in the Southern Hemisphere trivalent vaccine. The aim of this study was to describe the genetic diversity of influenza A (H3N2) viruses circulating in Brazil between January 2017 and January 2018, checking the match between the vaccines and worldwide circulating strains with the Brazilian influenza strains. Hemagglutinin gene sequencing of the influenza A (H3N2) was performed, followed by a phylogenetic reconstruction using additional database sequences to define genetic groups and compare with other worldwide circulating strains. We observed a large diversity of H3N2 genetic clusters, including 3C.2a, 3C.2a1, 3C.3a, and their subgroups. During the 2016–7, inter-epidemic and 2017 epidemic period the cluster most frequently detected belonged to clade 3C.2a1 (148/185; 80.0%), a distinct group related to the 2017 vaccine strain A/HongKong/4801/2014-like (3C.2a). However, the genetic profile changed during the study period and in the inter-epidemic season 2017–8 the most commonly detected genetic group was the 3C.2a cluster (43/58; 74.1%). Inside this cluster, the majority (34/43; 79.1%) of strains belonged to a single genetic 3C.2a subgroup 2 (3C.2a2), bearing antigenic substitutions T131K and R142K (site A) and R261Q (site E). The dominance of this 3C.2a2 in the 2017–8 inter-epidemic period in Brazil was similar to the 2017–8 season in Europe and Canada according their surveillance data. The new vaccine strain has five to six antigenic changes in comparison to the predominant 3C.2a2 circulating in South America since September 2017 until now. It is possible that the vaccine mismatch will not protect the population against a majority of circulating strains. Surveillance of the vaccine effectiveness supported by antigenic and serological analysis are necessary to prove this hypothesis. However, this highlights the difficulty of vaccine strain selection and highlights the need for of a universal influenza vaccine.

scholarly journals The prediction of Influenza A/H3N2 Vaccine Efficacy using samples obtained from Indonesian Hajj pilgrims in 2013

2018 ◽  
Vol 9 (1) ◽  
pp. 1-7
Author(s):  
Agustiningsih Agustiningsih ◽  
Kartika Dewi Puspa ◽  
Hartanti Dian Ikawati ◽  
Eka Pratiwi ◽  
Ririn Ramadhany ◽  
...  
Keyword(s):  
Amino Acid ◽  
Influenza Vaccine ◽  
Vaccine Strain ◽  
Vaccine Efficacy ◽  
Influenza A ◽  
Influenza Viruses ◽  
Health Science ◽  
H3n2 Virus ◽  
Science Journal ◽  
Virus Influenza

Abstrak Latar Belakang: Vaksinasi merupakan salah satu cara efektif dalam mengontrol dan mengurangi beban penyakit yang disebabkan oleh Influenza. Akan tetapi, efikasi vaksin bisa bervariasi jika strain yang digunakan untuk vaksin berbeda dengan strain yang bersirkulasi di dunia. Hal ini menunjukan pentingnya melakukan analisa prediksi efikasi vaksin. Pada studi ini, prediksi efikasi vaksin Influenza A/H3N2 dilakukan berdasarkan perhitungan antigenic distance strain vaksin WHO dengan virus influenza yang berasal dari jemaah Haj iIndonesia pada tahun 2013. Metode: Sekuensing gen HA dilakukan terhadap dua sampel tersimpan yang terkonfirmasi positif Influenza A/ H3N2 yang berasal dari jemaah Haji Indonesia tahun 2013. Pepitope Calculator digunakan untuk menghitung antigenic distance dari dua strain virus influenza dan dilanjutkan dengan perhitungan Pepitope value. Vaksin strain yang direkomendasikan oleh WHO; A/Texas/50/2012, A/Switzerland/9715293/2013, A/HongKong/4801/2014 dan dua virus yang diambil dari jemaah Haji Indonesia pada tahun 2013 dianalisa pada studi ini. Hasil: Prediksi efikasi vaksin yang direkomendasikan WHO tahun 2013 (A/Texas/50/2012) dengan sampel yang berasal dari jemaah Haji Indonesia tahun 2013 menunjukkan hasil lebih rendah dibandingkan dengan strain vaksin untuk musim flu pada tahun selanjutnya. Hasil ini sesuai dengan hasil analisis filogenetik dan perbandingan asam amino dimana sampel pada studi ini berkerabat lebih dekat dengan strain vaksin untuk musim flu selanjutnya dengan perbedaan asam amino yang lebih sedikit di bagian epitope protein HA dibandingkan dengan vaksin tahun 2013. Kesimpulan: Perhitungan efikasi vaksin menggunakan antigenic distance antara strain vaksin WHO dan virus yang menginfeksi jemaah haji Indonesia pada tahun 2013 menunjukkan hasil yang rendah. (Health Science Journal of Indonesia 2018;9(1):1-7) Keywords: Efikasi vaksin, Influenza A/H3N2, jemaah Haji, Indonesia Abstract Background: Influenza vaccination is an effective approach to control and reduce the disease burden of influenza viruses. However, the efficacy of influenza vaccine varies every year due to the different antigenic distance between vaccine and the circulating influenza strains globally and therefore necessitates the study of vaccine efficacy (VE). This study describes the prediction of Influenza A/H3N2 VE based on antigenic distances WHO vaccine strains and the virus obtained from Indonesian Hajj pilgrims in 2013. Methods: Coding between Sequence of HA gene of Influenza A/H3N2 virus was obtained from archival samples of Indonesian Hajj Pilgrims in 2013. Pepitope value calculation using Pepitope Calculator to measure the antigenic distance of HA sequences of two influenza strains was implemented. The HA sequences of WHO vaccine strains: A/ Texas/50/2012, A/Switzerland/9715293/2013, A/HongKong/4801/2014 and two influenza viruses from Indonesian Hajj pilgrims in 2013 were analyzed. Results: This study predicted that influenza vaccine strain recommended by WHO for 2013 (A/Texas/50/2012) have low efficacy to the influenza virus obtained from Indonesian Hajj Pilgrim in 2013 while showing higher efficacy to vaccine strain recommended for the following year. This result was in line with phylogenetic analysis and amino acid differences in which the samples in this study were grouped together with vaccine strain in following years and had less amino acid differences in epitope located in HA protein compared with 2013 vaccine strain. Conclusion: The prediction of VE using the antigenic distance measurement between WHO vaccine strain and Indonesian Hajj pilgrim collected in 2013, is considered low. (Health Science Journal of Indonesia 2018;9(1):1-7) Keywords: Vaccine efficacy, influenza A/H3N2 virus, Hajj pilgrim, Indonesia

scholarly journals PROBLEMS OF ISOLATION, IDENTIFICATION AND ANTIGENIC CHARACTERIZATION OF RECENT HUMAN A(H3N2) INFLUENZA VIRUSES

2018 ◽  
Vol 63 (4) ◽  
pp. 160-164
Author(s):  
P. A. Petrova ◽  
N. I. Konovalova ◽  
D. M. Danilenko ◽  
A. D. Vasilieva ◽  
M. Yu. Eropkin
Keyword(s):  
Influenza A ◽  
Influenza Viruses ◽  
High Rate ◽  
Influenza Vaccines ◽  
Antigenic Analysis ◽  
Hemagglutination Inhibition Test ◽  
Glycosylation Sites ◽  
Antigenic Properties ◽  
H3n2 Influenza ◽  
Selection Of

Human A (H3N2) influenza viruses are distinguished by a high rate of evolution and regularly cause epidemics around the world. Their ability to adapt and to escape from the host's immune response and to change their receptor specificity is very high. Over the past 20 years, these viruses have lost the ability to agglutinate red blood cells of chickens and turkeys and have practically ceased to propagate in chicken embryos - the main source of influenza vaccines. Isolation of viruses in the MDCK cell culture led to the selection of strains that lose one of the potential glycosylation sites. Many of the A (H3N2) strains have acquired mutations in neuraminidase, which distort the results of antigenic analysis in the hemagglutination inhibition test - the cornerstone method for the analysis of the match between viral isolates circulating in human population to strains selected for the influenza vaccines. In this regard, the characteristics of the antigenic properties of influenza A (H3N2) viruses by traditional methods become poorly informative, and the selection of vaccine strains of this subtype is erroneous, which is reflected in the discrepancy between vaccine and circulating A (H3N2) viruses in recent years (2013-2014, 2014 -2015, 2015-2016). The search, development and implementation of new algorithms for the isolation and antigen analysis of influenza A (H3N2) viruses are extremely urgent.

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