scholarly journals Improvement of influenza vaccine strain A/Vietnam/1194/2004 (H5N1) growth with the neuraminidase packaging sequence from A/Puerto Rico/8/34

2012 ◽  
Vol 8 (2) ◽  
pp. 252-259 ◽  
Author(s):  
Weiqi Pan ◽  
Zhenyuan Dong ◽  
Weixu Meng ◽  
Wei Zhang ◽  
Ting Li ◽  
...  
Keyword(s):  
Puerto Rico ◽  
Influenza Vaccine ◽  
Vaccine Strain ◽  
Packaging Sequence

scholarly journals Generation of a Genetically Stable High-Fidelity Influenza Vaccine Strain

2017 ◽  
Vol 91 (6) ◽  
Author(s):  
Tadasuke Naito ◽  
Kotaro Mori ◽  
Hiroshi Ushirogawa ◽  
Naoki Takizawa ◽  
Eri Nobusawa ◽  
...  
Keyword(s):  
Puerto Rico ◽  
Influenza Vaccine ◽  
Vaccine Strain ◽  
Error Rate ◽  
High Growth ◽  
Vaccine Virus ◽  
High Fidelity ◽  
Reassortant Virus ◽  
H1n1 Vaccine ◽  
Ha Gene

ABSTRACT Vaccination is considered the most effective preventive means for influenza control. The development of a master virus with high growth and genetic stability, which may be used for the preparation of vaccine viruses by gene reassortment, is crucial for the enhancement of vaccine performance and efficiency of production. Here, we describe the generation of a high-fidelity and high-growth influenza vaccine master virus strain with a single V43I amino acid change in the PB1 polymerase of the high-growth A/Puerto Rico/8/1934 (PR8) master virus. The PB1-V43I mutation was introduced to increase replication fidelity in order to design an H1N1 vaccine strain with a low error rate. The PR8-PB1-V43I virus exhibited good replication compared with that of the parent PR8 virus. In order to compare the efficiency of egg adaptation and the occurrence of gene mutations leading to antigenic alterations, we constructed 6:2 genetic reassortant viruses between the A(H1N1)pdm09 and the PR8-PB1-V43I viruses; hemagglutinin (HA) and neuraminidase (NA) were from the A(H1N1)pdm09 virus, and the other genes were from the PR8 virus. Mutations responsible for egg adaptation mutations occurred in the HA of the PB1-V43I reassortant virus during serial egg passages; however, in contrast, antigenic mutations were introduced into the HA gene of the 6:2 reassortant virus possessing the wild-type PB1. This study shows that the mutant PR8 virus possessing the PB1 polymerase with the V43I substitution may be utilized as a master virus for the generation of high-growth vaccine viruses with high polymerase fidelity, low error rates of gene replication, and reduced antigenic diversity during virus propagation in eggs for vaccine production. IMPORTANCE Vaccination represents the most effective prophylactic option against influenza. The threat of emergence of influenza pandemics necessitates the ability to generate vaccine viruses rapidly. However, as the influenza virus exhibits a high mutation rate, vaccines must be updated to ensure a good match of the HA and NA antigens between the vaccine and the circulating strain. Here, we generated a genetically stable master virus of the A/Puerto Rico/8/1934 (H1N1) backbone encoding an engineered high-fidelity viral polymerase. Importantly, following the application of the high-fidelity PR8 backbone, no mutation resulting in antigenic change was introduced into the HA gene during propagation of the A(H1N1)pdm09 candidate vaccine virus. The low error rate of the present vaccine virus should decrease the risk of generating mutant viruses with increased virulence. Therefore, our findings are expected to be useful for the development of prepandemic vaccines and live attenuated vaccines with higher safety than that of the present candidate vaccines.

scholarly journals Antigenic assessment of the H3N2 component of the 2019-2020 Northern Hemisphere influenza vaccine

2020 ◽  
Author(s):  
Sigrid Gouma ◽  
Madison Weirick ◽  
Scott E. Hensley
Keyword(s):  
Influenza Vaccine ◽  
Northern Hemisphere ◽  
Vaccine Strain ◽  
Antibody Responses ◽  
Wild Type ◽  
H3n2 Vaccine

AbstractThe 2019-2020 Northern Hemisphere influenza vaccine includes antigens from 3c3.A H3N2 viruses; however, over half of circulating H3N2 viruses belong to subclade 3c2.A1b. Here, we analyzed antibody responses elicited by the egg-adapted 3c3.A H3N2 vaccine strain in ferrets and humans. We found that this vaccine strain elicits antibodies that have reduced reactivity to a wild-type 3c3.A strain and very limited reactivity to 3c2.A strains, including the currently circulating 3c2.A1b strain.

scholarly journals Identification of human vaccinees that possess antibodies targeting the egg-adapted hemagglutinin receptor binding site of an H1N1 influenza vaccine strain

Vaccine ◽  
2018 ◽  
Vol 36 (28) ◽  
pp. 4095-4101 ◽  
Author(s):  
Tyler A. Garretson ◽  
Joshua G. Petrie ◽  
Emily T. Martin ◽  
Arnold S. Monto ◽  
Scott E. Hensley
Keyword(s):  
Influenza Vaccine ◽  
Binding Site ◽  
Vaccine Strain ◽  
Receptor Binding ◽  
H1n1 Influenza ◽  
Receptor Binding Site

scholarly journals Assessment of Antigen-Specific and Cross-Reactive Antibody Responses to an MF59-Adjuvanted A/H5N1 Prepandemic Influenza Vaccine in Adult and Elderly Subjects

2012 ◽  
Vol 19 (12) ◽  
pp. 1943-1948 ◽  
Author(s):  
Iván Bihari ◽  
Gyula Pánczél ◽  
Jozsef Kovacs ◽  
Jenny Beygo ◽  
Elena Fragapane
Keyword(s):  
Influenza Vaccine ◽  
Vaccine Strain ◽  
Influenza Pandemic ◽  
Vaccine Dose ◽  
The Elderly ◽  
Antibody Responses ◽  
Elderly Subjects ◽  
H5n1 Influenza ◽  
Reactive Antibody ◽  
Heterologous Antibody

ABSTRACTPreparedness against an A/H5N1 influenza pandemic requires well-tolerated, effective vaccines which provide both vaccine strain-specific and heterologous, cross-clade protection. This study was conducted to assess the immunogenicity and safety profile of an MF59-adjuvanted, prepandemic influenza vaccine containing A/turkey/Turkey/01/2005 (H5N1) strain viral antigen. A total of 343 participants, 194 adults (18 to 60 years) and 149 elderly individuals (≥61 years), received two doses of the investigational vaccine given 3 weeks apart. Homologous and heterologous antibody responses were analyzed by hemagglutination inhibition (HI), single radial hemolysis (SRH), and microneutralization (MN) assays 3 weeks after administration of the first vaccine dose and 3 weeks and 6 months after the second dose. Immunogenicity was assessed according to European licensure criteria for pandemic influenza vaccines. After two vaccine doses, all three European licensure criteria were met for adult and elderly subjects against the homologous vaccine strain, A/turkey/Turkey/1/2005, when analyzed by HI and SRH assays. Cross-reactive antibody responses were observed by HI and SRH analyses against the heterologous H5N1 strains, A/Indonesia/5/2005 and A/Vietnam/1194/2004, in adult and elderly subjects. Solicited local and systemic reactions were mostly mild to moderate in severity and occurred less frequently in the elderly than in adult vaccinees. In both adult and elderly subjects, MF59-adjuvanted vaccine containing 7.5 μg of A/Turkey strain influenza virus antigen was highly immunogenic, well tolerated, and able to elicit cross-clade, heterologous antibody responses against A/Indonesia and A/Vietnam strains 6 weeks after the first vaccination.

scholarly journals IgE-RESPONSE AFTER ADMINISTRATION OF PANDEMIC VACCINE STRAIN A/CALIFORNIA/7/2009 (H1N1) v

2012 ◽  
Vol 67 (10) ◽  
pp. 44-48
Author(s):  
M. P. Kostinov ◽  
O. A. Terkacheva ◽  
S. N. Zhirova ◽  
A. P. Cherdanchev ◽  
M. K. Erofeeva
Keyword(s):  
Influenza Vaccine ◽  
Healthy Volunteers ◽  
Vaccine Strain ◽  
Specific Ige ◽  
Dose Administration ◽  
Ige Antibodies ◽  
2009 H1n1 ◽  
Ige Response ◽  
Egg Components ◽  
Pandemic Vaccine

Changes in total and allergy-specific IgE (IgE-antibodies) in 70 healthy volunteers vaccinated with influenza vaccine subunit strain A/California/7/2009/(H1N1). Safety of this vaccine was shown. Repeated second dose administration is not accompanied by increase in IgE-antibodies to egg components. Vaccine injection results in decrease of total IgE in patients with elevated IgE at baseline. 

scholarly journals 10. Quadrivalent M2SR (M2-deficient Single Replication) Live Influenza Vaccine Provides Better Protection Than Inactivated Vaccine Against Drifted Influenza B Virus Challenge in Ferrets

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S128-S129
Author(s):  
Lindsay Hill-Batorski ◽  
Yasuko Hatta ◽  
Michael Moser ◽  
David Marshall ◽  
Pamuk Bilsel
Keyword(s):  
Body Weight ◽  
Detection Limit ◽  
Influenza Vaccine ◽  
Vaccine Strain ◽  
Virus Titer ◽  
Influenza B ◽  
Post Challenge ◽  
Post Vaccination ◽  
Challenge Virus ◽  
Temperature Changes

Abstract Background Quadrivalent inactivated influenza vaccines (QIV) induce neutralizing antibodies (Abs) against the viral hemagglutinin (HA). Despite annual update of HA vaccine antigens to match circulating strains, current vaccines provide ~60% vaccine effectiveness (VE). QIV VE can be as low as 10% when circulating strains do not match vaccine HA. The live M2SR (M2-deficient single replication) influenza vaccine candidate has previously shown broad humoral, mucosal and cellular immune responses and protection against multiple influenza A subtypes. Here we show similar properties with the Quadrivalent M2SR (Quad M2SR) against drifted influenza B challenge in comparison to QIV. Methods Ferrets pre-infected with influenza H1N1 and B/Yamagata viruses, were immunized intranasally (IN) with PBS (Mock) or Quad M2SR, or intramuscularly with Fluzone QIV. Serum collected post-vaccination was evaluated for Ab responses. Forty-two days after vaccination, ferrets were challenged IN with 106 pfu of B/Brisbane/60/2008 (Victoria lineage) influenza virus. Nasal washes were taken for 7 days post-challenge and evaluated for challenge virus by TCID50 assay. Nasal turbinates, trachea and lungs were also evaluated for virus. Results Quad M2SR and QIV elicited high serum Abs against the vaccine strain B/Colorado/06/2017 (Fig. 1A) and against the drifted influenza B challenge strain B/Brisbane/60/2008 (Fig. 1B) in ferrets with preexisting immunity. Like Mock, ferrets who received QIV displayed both weight loss (6.2%, Fig. 2A) and a rise in temperature (1.1oC, Fig. 2B) after challenge. In contrast, the Quad M2SR group did not exhibit any significant weight or temperature changes after challenge. Quad M2SR controlled the drifted challenge virus better than QIV as evidenced by significantly lower or absent post-challenge virus titer in nasal washes (Fig. 3A) and nasal turbinates (Fig. 3B). Figure 1. Serum Neutralization Titers Post-Vaccination Plaque reduction neutralization test (PRNT) antibody titers for Quad M2SR and QIV against matched Influenza B vaccine strain B/Colorado/06/2017 (Fig. 1A) and drifted strain B/Brisbane/60/2008 (Fig. 1B) on pre-study (Day -3), pre-vaccination (Day 28), and 3 weeks post vaccination (Day 51). The detection limit of the assay (horizontal dashed line) was 15 PRNT50. Figure 2. Post-challenge body weight and temperature changes Percent body weight changes (Fig. 2A) and average body temperatures changes (Fig. 2B) following challenge with drifted Influenza B strain B/Brisbane/60/2008 for ferrets vaccinated with Quad M2SR or QIV. Figure 3. Post-challenge virus titers in respiratory tract. Viral titers in nasal washes (Fig. 3A) and nasal turbinates (Fig. 3B) collected post-challenge with Influenza B strain B/Brisbane/60/2008 in ferrets vaccinated with Quad M2SR or QIV. No virus was detected in the trachea or lungs. The detection limit of the assay (horizontal dashed line) was 1.5 log10 TCID50/mL and 20 FFU respectively. Virus titer between groups was significant on day 3 of the nasal washes: one-way analysis of variance (ANOVA) with Multiple t tests to compare between groups, #p<0.05,><0.01,><> Conclusion Despite eliciting similar Ab titers, the Quad M2SR demonstrated superior protection compared to QIV in a drifted influenza B challenge model in ferrets. These results suggest that the intranasal M2SR platform may confer additional advantages over currently available vaccines. Quad M2SR is in late-stage development for testing in a first-in-human clinical study. Disclosures Lindsay Hill-Batorski, PhD, FluGen (Employee) Yasuko Hatta, DVM, PhD, FluGen (Employee) Michael Moser, PhD, FluGen (Employee) David Marshall, BS, FluGen (Employee) Pamuk Bilsel, PhD, FluGen (Employee)

A single amino acid change in hemagglutinin reduces the cross-reactivity of antiserum against an equine influenza vaccine strain

2019 ◽  
Vol 164 (9) ◽  
pp. 2355-2358
Author(s):  
Manabu Nemoto ◽  
Seiya Yamayoshi ◽  
Hiroshi Bannai ◽  
Koji Tsujimura ◽  
Hiroshi Kokado ◽  
...  
Keyword(s):  
Amino Acid ◽  
Influenza Vaccine ◽  
Vaccine Strain ◽  
Amino Acid Change ◽  
Cross Reactivity ◽  
Single Amino Acid ◽  
Equine Influenza ◽  
Single Amino Acid Change ◽  
The Cross

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.

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