Optimization of M2e cassette amino acid composition for the development of universal influenza vaccine

2021 ◽  
Vol 21 (3) ◽  
pp. 127-130
Author(s):  
Daria А. Mezhenskaya ◽  
Irina N. Isakova-Sivak ◽  
Anastasiya E. Katelnikova ◽  
Larisa G. Rudenko
Keyword(s):  
Public Health ◽  
Amino Acid ◽  
Influenza Vaccine ◽  
Influenza A ◽  
Wide Spectrum ◽  
Qualitative Assessment ◽  
Influenza A Viruses ◽  
Duration Of Action ◽  
Natural Reservoir ◽  
Universal Influenza Vaccine

The development of a universal influenza vaccine with a wide spectrum and duration of action is one of the serious public health problems. This study is dedicated to optimization of an immunogen covering the M2e epitopes of influenza A viruses circulating in the natural reservoir, as well as the creation of a prototype of a universal influenza vaccine with subsequent quantitative and qualitative assessment of the induced anti-M2e responses in ferrets.

scholarly journals An Intranasal Virus-Like Particle Vaccine Broadly Protects Mice from Multiple Subtypes of Influenza A Virus

mBio ◽  
2015 ◽  
Vol 6 (4) ◽  
Author(s):  
Louis M. Schwartzman ◽  
Andrea L. Cathcart ◽  
Lindsey M. Pujanauski ◽  
Li Qi ◽  
John C. Kash ◽  
...  
Keyword(s):  
Public Health ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Viruses ◽  
Significant Protection ◽  
Virus Infections ◽  
Influenza A Viruses ◽  
Virus Like Particle ◽  
Practical Strategy ◽  
Universal Influenza Vaccine

ABSTRACTInfluenza virus infections are a global public health problem, with a significant impact of morbidity and mortality from both annual epidemics and pandemics. The current strategy for preventing annual influenza is to develop a new vaccine each year against specific circulating virus strains. Because these vaccines are unlikely to protect against an antigenically divergent strain or a new pandemic virus with a novel hemagglutinin (HA) subtype, there is a critical need for vaccines that protect against all influenza A viruses, a so-called “universal” vaccine. Here we show that mice were broadly protected against challenge with a wide variety of lethal influenza A virus infections (94% aggregate survival following vaccination) with a virus-like particle (VLP) vaccine cocktail. The vaccine consisted of a mixture of VLPs individually displaying H1, H3, H5, or H7 HAs, and vaccinated mice showed significant protection following challenge with influenza viruses expressing 1918 H1, 1957 H2, and avian H5, H6, H7, H10, and H11 hemagglutinin subtypes. These experiments suggest a promising and practical strategy for developing a broadly protective “universal” influenza vaccine.IMPORTANCEThe rapid and unpredictable nature of influenza A virus evolution requires new vaccines to be produced annually to match circulating strains. Human infections with influenza viruses derived from animals can cause outbreaks that may be associated with high mortality, and such strains may also adapt to humans to cause a future pandemic. Thus, there is a large public health need to create broadly protective, or “universal,” influenza vaccines that could prevent disease from a wide variety of human and animal influenza A viruses. In this study, a noninfectious virus-like particle (VLP) vaccine was shown to offer significant protection against a variety of influenza A viruses in mice, suggesting a practical strategy to develop a universal influenza vaccine.

scholarly journals Cross-Reactive Neuraminidase-Inhibiting Antibodies Elicited by Immunization with Recombinant Neuraminidase Proteins of H5N1 and Pandemic H1N1 Influenza A Viruses

2015 ◽  
Vol 89 (14) ◽  
pp. 7224-7234 ◽  
Author(s):  
Wen-Chun Liu ◽  
Chia-Ying Lin ◽  
Yung-Ta Tsou ◽  
Jia-Tsrong Jan ◽  
Suh-Chin Wu
Keyword(s):  
Influenza Virus ◽  
Sialic Acid ◽  
Influenza Vaccine ◽  
Influenza A ◽  
Expression System ◽  
Influenza Viruses ◽  
Pandemic H1n1 ◽  
Influenza A Viruses ◽  
Homologous Virus ◽  
Universal Influenza Vaccine

ABSTRACTNeuraminidase (NA), an influenza virus envelope glycoprotein, removes sialic acid from receptors for virus release from infected cells. For this study, we used a baculovirus-insect cell expression system to construct and purify recombinant NA (rNA) proteins of H5N1 (A/Vietnam/1203/2004) and pandemic H1N1 (pH1N1) (A/Texas/05/2009) influenza viruses. BALB/c mice immunized with these proteins had high titers of NA-specific IgG and NA-inhibiting (NI) antibodies against H5N1, pH1N1, H3N2, and H7N9 viruses. H5N1 rNA immunization resulted in higher quantities of NA-specific antibody-secreting B cells against H5N1 and heterologous pH1N1 viruses in the spleen. H5N1 rNA and pH1N1 rNA immunizations both provided complete protection against homologous virus challenges, with H5N1 rNA immunization providing better protection against pH1N1 virus challenges. Cross-reactive NI antibodies were further dissected via pH1N1 rNA protein immunizations with I149V (NA with a change of Ile to Val at position 149), N344Y, and I365T/S366N NA mutations. The I365T/S366N mutation of pH1N1 rNA enhanced cross-reactive NI antibodies against H5N1, H3N2, and H7N9 viruses. It is our hope that these findings provide useful information for the development of an NA-based universal influenza vaccine.IMPORTANCENeuraminidase (NA) is an influenza virus enzymatic protein that cleaves sialic acid linkages on infected cell surfaces, thus facilitating viral release and contributing to viral transmission and mucus infection. In currently available inactivated or live, attenuated influenza vaccines based on the antigenic content of hemagglutinin proteins, vaccine efficacy can be contributed partly through NA-elicited immune responses. We investigated the NA immunity of different recombinant NA (rNA) proteins associated with pH1N1 and H5N1 viruses. Our results indicate that H5N1 rNA immunization induced more potent cross-protective immunity than pH1N1 rNA immunization, and three mutated residues, I149V, I365T, and S366N, near the NA enzyme active site(s) are linked to enhanced cross-reactive NA-inhibiting antibodies against heterologous and heterosubtypic influenza A viruses. These findings provide useful information for the development of an NA-based universal influenza vaccine.

scholarly journals Machine Learning Prediction and Experimental Validation of Antigenic Drift in H3 Influenza A Viruses in Swine

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Michael A. Zeller ◽  
Phillip C. Gauger ◽  
Zebulun W. Arendsee ◽  
Carine K. Souza ◽  
Amy L. Vincent ◽  
...  
Keyword(s):  
Public Health ◽  
Amino Acid ◽  
Regression Models ◽  
Influenza A ◽  
Sequence Data ◽  
Antigenic Drift ◽  
Influenza A Viruses ◽  
Genetic Sequence ◽  
Nonlinear Regression Models ◽  
Antigenic Phenotype

ABSTRACT The antigenic diversity of influenza A viruses (IAV) circulating in swine challenges the development of effective vaccines, increasing zoonotic threat and pandemic potential. High-throughput sequencing technologies can quantify IAV genetic diversity, but there are no accurate approaches to adequately describe antigenic phenotypes. This study evaluated an ensemble of nonlinear regression models to estimate virus phenotype from genotype. Regression models were trained with a phenotypic data set of pairwise hemagglutination inhibition (HI) assays, using genetic sequence identity and pairwise amino acid mutations as predictor features. The model identified amino acid identity, ranked the relative importance of mutations in the hemagglutinin (HA) protein, and demonstrated good prediction accuracy. Four previously untested IAV strains were selected to experimentally validate model predictions by HI assays. Errors between predicted and measured distances of uncharacterized strains were 0.35, 0.61, 1.69, and 0.13 antigenic units. These empirically trained regression models can be used to estimate antigenic distances between different strains of IAV in swine by using sequence data. By ranking the importance of mutations in the HA, we provide criteria for identifying antigenically advanced IAV strains that may not be controlled by existing vaccines and can inform strain updates to vaccines to better control this pathogen. IMPORTANCE Influenza A viruses (IAV) in swine constitute a major economic burden to an important global agricultural sector, impact food security, and are a public health threat. Despite significant improvement in surveillance for IAV in swine over the past 10 years, sequence data have not been integrated into a systematic vaccine strain selection process for predicting antigenic phenotype and identifying determinants of antigenic drift. To overcome this, we developed nonlinear regression models that predict antigenic phenotype from genetic sequence data by training the model on hemagglutination inhibition assay results. We used these models to predict antigenic phenotype for previously uncharacterized IAV, ranked the importance of genetic features for antigenic phenotype, and experimentally validated our predictions. Our model predicted virus antigenic characteristics from genetic sequence data and provides a rapid and accurate method linking genetic sequence data to antigenic characteristics. This approach also provides support for public health by identifying viruses that are antigenically advanced from strains used as pandemic preparedness candidate vaccine viruses.

scholarly journals Characterization of H9N2 influenza A viruses isolated from chicken products imported into Japan from China

2006 ◽  
Vol 135 (3) ◽  
pp. 386-391 ◽  
Author(s):  
M. MASE ◽  
M. ETO ◽  
K. IMAI ◽  
K. TSUKAMOTO ◽  
S. YAMAGUCHI
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Influenza A ◽  
H9n2 Virus ◽  
Amino Acid Substitutions ◽  
Influenza A Viruses ◽  
Potential Sources

We characterized eleven H9N2 influenza A viruses isolated from chicken products imported from China. Genetically they were classified into six distinct genotypes, including five already known genotypes and one novel genotype. This suggested that such multiple genotypes of the H9N2 virus have possibly already become widespread and endemic in China. Two isolates have amino-acid substitutions that confer resistance to amantadine in the M2 region, and this supported the evidence that this mutation might be a result of the wide application of amantadine for avian influenza treatment in China. These findings emphasize the importance of surveillance for avian influenza virus in this region, and of quarantining imported chicken products as potential sources for the introduction of influenza virus.

scholarly journals Plasticity of the Influenza Virus H5 HA Protein

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Huihui Kong ◽  
David F. Burke ◽  
Tiago Jose da Silva Lopes ◽  
Kosuke Takada ◽  
Masaki Imai ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
Mammalian Cells ◽  
Influenza A ◽  
Viral Antigen ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
Highly Pathogenic ◽  
Antigenic Properties ◽  
Ha Protein

ABSTRACT Since the emergence of highly pathogenic avian influenza viruses of the H5 subtype, the major viral antigen, hemagglutinin (HA), has undergone constant evolution, resulting in numerous genetic and antigenic (sub)clades. To explore the consequences of amino acid changes at sites that may affect the antigenicity of H5 viruses, we simultaneously mutated 17 amino acid positions of an H5 HA by using a synthetic gene library that, theoretically, encodes all combinations of the 20 amino acids at the 17 positions. All 251 mutant viruses sequenced possessed ≥13 amino acid substitutions in HA, demonstrating that the targeted sites can accommodate a substantial number of mutations. Selection with ferret sera raised against H5 viruses of different clades resulted in the isolation of 39 genotypes. Further analysis of seven variants demonstrated that they were antigenically different from the parental virus and replicated efficiently in mammalian cells. Our data demonstrate the substantial plasticity of the influenza virus H5 HA protein, which may lead to novel antigenic variants. IMPORTANCE The HA protein of influenza A viruses is the major viral antigen. In this study, we simultaneously introduced mutations at 17 amino acid positions of an H5 HA expected to affect antigenicity. Viruses with ≥13 amino acid changes in HA were viable, and some had altered antigenic properties. H5 HA can therefore accommodate many mutations in regions that affect antigenicity. The substantial plasticity of H5 HA may facilitate the emergence of novel antigenic variants.

scholarly journals Public health implications of influenza B outbreaks in closed settings in the United Kingdom in the 2007/08 influenza season

2008 ◽  
Vol 13 (38) ◽  
Author(s):  
P Mook ◽  
J Ellis ◽  
J M Watson ◽  
CI Thompson ◽  
M Zambon ◽  
...  
Keyword(s):  
Public Health ◽  
United Kingdom ◽  
Burden Of Disease ◽  
Influenza A ◽  
Health Management ◽  
Influenza Season ◽  
Influenza B ◽  
Influenza A Viruses ◽  
School Aged Children ◽  
The United Kingdom

Several influenza B outbreaks occurred in closed settings late in the 2007/08 influenza season (October to mid-May) in the United Kingdom (UK), with implications for public health management. Influenza B viruses usually circulate late in the season and cause a milder disease than influenza A viruses [1]. Epidemics of influenza B usually occur every two to three years with the burden of disease falling predominantly on school-aged children [2].

scholarly journals Genetic and Antigenic Evolution of European Swine Influenza A Viruses of HA-1C (Avian-Like) and HA-1B (Human-Like) Lineages in France from 2000 to 2018

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1304
Author(s):  
Amélie Chastagner ◽  
Séverine Hervé ◽  
Stéphane Quéguiner ◽  
Edouard Hirchaud ◽  
Pierrick Lucas ◽  
...  
Keyword(s):  
Amino Acid ◽  
Influenza A ◽  
Phylogenetic Analyses ◽  
Swine Influenza ◽  
Amino Acid Sequences ◽  
Antigenic Drift ◽  
Influenza A Viruses ◽  
Double Deletion ◽  
Antigenic Evolution ◽  
Amino Acid Mutations

This study evaluated the genetic and antigenic evolution of swine influenza A viruses (swIAV) of the two main enzootic H1 lineages, i.e., HA-1C (H1av) and -1B (H1hu), circulating in France between 2000 and 2018. SwIAV RNAs extracted from 1220 swine nasal swabs were hemagglutinin/neuraminidase (HA/NA) subtyped by RT-qPCRs, and 293 virus isolates were sequenced. In addition, 146 H1avNy and 105 H1huNy strains were submitted to hemagglutination inhibition tests. H1avN1 (66.5%) and H1huN2 (25.4%) subtypes were predominant. Most H1 strains belonged to HA-1C.2.1 or -1B.1.2.3 clades, but HA-1C.2, -1C.2.2, -1C.2.3, -1B.1.1, and -1B.1.2.1 clades were also detected sporadically. Within HA-1B.1.2.3 clade, a group of strains named “Δ146-147” harbored several amino acid mutations and a double deletion in HA, that led to a marked antigenic drift. Phylogenetic analyses revealed that internal segments belonged mainly to the “Eurasian avian-like lineage”, with two distinct genogroups for the M segment. In total, 17 distinct genotypes were identified within the study period. Reassortments of H1av/H1hu strains with H1N1pdm virus were rarely evidenced until 2018. Analysis of amino acid sequences predicted a variability in length of PB1-F2 and PA-X proteins and identified the appearance of several mutations in PB1, PB1-F2, PA, NP and NS1 proteins that could be linked to virulence, while markers for antiviral resistance were identified in N1 and N2. Altogether, diversity and evolution of swIAV recall the importance of disrupting the spreading of swIAV within and between pig herds, as well as IAV inter-species transmissions.

scholarly journals Computational Approaches and Challenges to Developing Universal Influenza Vaccines

Vaccines ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 45 ◽  
Author(s):  
Xueting Qiu ◽  
Venkata R. Duvvuri ◽  
Justin Bahl
Keyword(s):  
Influenza Vaccine ◽  
Influenza A ◽  
Low Cost ◽  
T Cell Epitopes ◽  
Computational Approaches ◽  
Novel Technologies ◽  
Consensus Sequences ◽  
Computational Optimization ◽  
Sequence Reconstruction ◽  
Universal Influenza Vaccine

The traditional design of effective vaccines for rapidly-evolving pathogens, such as influenza A virus, has failed to provide broad spectrum and long-lasting protection. With low cost whole genome sequencing technology and powerful computing capabilities, novel computational approaches have demonstrated the potential to facilitate the design of a universal influenza vaccine. However, few studies have integrated computational optimization in the design and discovery of new vaccines. Understanding the potential of computational vaccine design is necessary before these approaches can be implemented on a broad scale. This review summarizes some promising computational approaches under current development, including computationally optimized broadly reactive antigens with consensus sequences, phylogenetic model-based ancestral sequence reconstruction, and immunomics to compute conserved cross-reactive T-cell epitopes. Interactions between virus-host-environment determine the evolvability of the influenza population. We propose that with the development of novel technologies that allow the integration of data sources such as protein structural modeling, host antibody repertoire analysis and advanced phylodynamic modeling, computational approaches will be crucial for the development of a long-lasting universal influenza vaccine. Taken together, computational approaches are powerful and promising tools for the development of a universal influenza vaccine with durable and broad protection.

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