scholarly journals Targeting Hemagglutinin: Approaches for Broad Protection against the Influenza A Virus

Viruses ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 405 ◽  
Author(s):  
Zhang ◽  
Xu ◽  
Zhang ◽  
Liu ◽  
Xue ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Protective Efficacy ◽  
Structure And Function ◽  
Antigenic Drift ◽  
Influenza A Viruses ◽  
Universal Vaccine ◽  
Vaccine Candidates ◽  
And Function ◽  
Ha Protein

Influenza A viruses are dynamically epidemic and genetically diverse. Due to the antigenic drift and shift of the virus, seasonal vaccines are required to be reformulated annually to match with current circulating strains. However, the mismatch between vaccinal strains and circulating strains occurs frequently, resulting in the low efficacy of seasonal vaccines. Therefore, several “universal” vaccine candidates based on the structure and function of the hemagglutinin (HA) protein have been developed to meet the requirement of a broad protection against homo-/heterosubtypic challenges. Here, we review recent novel constructs and discuss several important findings regarding the broad protective efficacy of HA-based universal vaccines.

scholarly journals Effects of single-point amino acid substitutions on the structure and function neuraminidase proteins in influenza A virus

2008 ◽  
Vol 52 (4) ◽  
pp. 216-223 ◽  
Author(s):  
Takuya Yano ◽  
Eri Nobusawa ◽  
Alexander Nagy ◽  
Setsuko Nakajima ◽  
Katsuhisa Nakajima
Keyword(s):  
Amino Acid ◽  
Influenza A Virus ◽  
Influenza A ◽  
Single Point ◽  
Structure And Function ◽  
Amino Acid Substitutions ◽  
And Function

scholarly journals octoFLU: Automated Classification for the Evolutionary Origin of Influenza A Virus Gene Sequences Detected in U.S. Swine

2019 ◽  
Vol 8 (32) ◽  
Author(s):  
Jennifer Chang ◽  
Tavis K. Anderson ◽  
Michael A. Zeller ◽  
Phillip C. Gauger ◽  
Amy L. Vincent
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Antigenic Drift ◽  
Evolutionary Origin ◽  
Automated Classification ◽  
Gene Sequences ◽  
Influenza A Viruses ◽  
Query Gene ◽  
Data Set ◽  
Virus Gene

The diversity of the 8 genes of influenza A viruses (IAV) in swine reflects introductions from nonswine hosts and subsequent antigenic drift and shift. Here, we curated a data set and present a pipeline that assigns evolutionary lineage and genetic clade to query gene segments.

scholarly journals Structure and Function of the NS1 Protein of Influenza A Virus

2007 ◽  
Vol 39 (3) ◽  
pp. 155-162 ◽  
Author(s):  
Dongzi LIN ◽  
Jingfang LAN ◽  
Zhizhen ZHANG
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Structure And Function ◽  
Ns1 Protein ◽  
And Function

scholarly journals Induction of Virus-Specific Cytotoxic T Lymphocytes as a Basis for the Development of Broadly Protective Influenza Vaccines

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Marine L. B. Hillaire ◽  
Albert D. M. E. Osterhaus ◽  
Guus F. Rimmelzwaan
Keyword(s):  
T Lymphocytes ◽  
Influenza A Virus ◽  
Cytotoxic T Lymphocytes ◽  
Influenza A ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Influenza Vaccines ◽  
Virus Infections ◽  
Influenza A Viruses ◽  
Heterosubtypic Immunity

There is considerable interest in the development of broadly protective influenza vaccines because of the continuous emergence of antigenic drift variants of seasonal influenza viruses and the threat posed by the emergence of antigenically distinct pandemic influenza viruses. It has been recognized more than three decades ago that influenza A virus-specific cytotoxic T lymphocytes recognize epitopes located in the relatively conserved proteins like the nucleoprotein and that they cross-react with various subtypes of influenza A viruses. This implies that these CD8+T lymphocytes may contribute to protective heterosubtypic immunity induced by antecedent influenza A virus infections. In the present paper, we review the evidence for the role of virus-specific CD8+T lymphocytes in protective immunity against influenza virus infections and discuss vaccination strategies that aim at the induction of cross-reactive virus-specific T-cell responses.

scholarly journals A multiplex real-time PCR assay for detection of oseltamivir-resistant strains of influenza virus

2014 ◽  
Vol 9 (6) ◽  
pp. 628-633
Author(s):  
Dawid Nidzworski ◽  
Joanna Dobkowska ◽  
Marcin Hołysz ◽  
Beata Gromadzka ◽  
Bogusław Szewczyk
Keyword(s):  
Real Time ◽  
Influenza A Virus ◽  
Real Time Pcr ◽  
Influenza A ◽  
Influenza Pandemic ◽  
Neuraminidase Inhibitor ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Influenza A Viruses ◽  
Oseltamivir Resistance

AbstractInfluenza is a contagious disease of humans and animals caused by viruses belonging to the Orthomyxoviridae family. The influenza A virus genome consists of negative sense, single-stranded, segmented RNA. Influenza viruses are classified into subtypes based on two surface antigens known as hemagglutinin (H) and neuraminidase (N). The main problem with influenza A viruses infecting humans is drug resistance, which is caused by antigenic changes. A few antiviral drugs are available, but the most popular is the neuraminidase inhibitor — oseltamivir. The resistance against this drug has probably developed through antigenic drift by a point mutation in one amino acid at position 275 (H275Y). In order to prevent a possible influenza pandemic it is necessary to develop fast diagnostic tests. The aim of this project was to develop a new test for detection of influenza A virus and determination of oseltamivir resistance/sensitivity in humans. Detection and differentiation of oseltamivir resistance/sensitivity of influenza A virus was based on real-time PCR. This test contains two TaqMan probes, which work at different wavelengths. Application of techniques like multiplex real-time PCR has greatly enhanced the capability for surveillance and characterization of influenza viruses. After its potential validation, this test can be used for diagnosis before treatment.

scholarly journals Immunologic studies on the influenza A virus nonstructural protein NS1.

1982 ◽  
Vol 156 (1) ◽  
pp. 243-254 ◽  
Author(s):  
M W Shaw ◽  
E W Lamon ◽  
R W Compans
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Nonstructural Protein ◽  
Antigenic Drift ◽  
Ns1 Protein ◽  
Influenza A Viruses ◽  
Cytoplasmic Inclusions ◽  
Infected Cells ◽  
Virus Isolates

We purified the major influenza virus nonstructural protein, designated NS1, from cytoplasmic inclusions that were solubilized and used to raise antisera in rabbits. One of the antisera was found to be specific for NS1 by complement fixation tests and analyses of immune precipitates. Antiserum to NS1 isolated from cells infected with A/WSN/33 virus specifically precipitated NS1 from extracts of cells infected with seven distinct isolates of influenza A virus representing five different antigenic subtypes. These included A/WSN/33, A/PR/8/34, A/FW/5/50, A/USSR/90/77, A/RI/5+/57, A/Victoria/3/75, and A/Swine /1977/31; however, NS1 from cells infected with B/Lee/40 virus was not precipitated. Radioimmunoassays using radioiodinated NS1 protein from A/WSN virus-infected cells and unlabeled cytoplasmic extracts of cells infected with various strains of influenza virus as competitors indicated significant antigenic cross-reactivities for the NS1 proteins of all influenza A viruses tested. The results suggest a gradual antigenic drift over the 45 yr separating the earliest and most recent virus isolates examined. Thus, compared with the virion neuraminidase and hemagglutinin antigens, NS1 appears to be highly conserved in different influenza A virus isolates.

scholarly journals The Molecular Determinants of Antibody Recognition and Antigenic Drift in the H3 Hemagglutinin of Swine Influenza A Virus

2016 ◽  
Vol 90 (18) ◽  
pp. 8266-8280 ◽  
Author(s):  
Eugenio J. Abente ◽  
Jefferson Santos ◽  
Nicola S. Lewis ◽  
Phillip C. Gauger ◽  
Jered Stratton ◽  
...  
Keyword(s):  
Amino Acid ◽  
Influenza A Virus ◽  
Influenza A ◽  
Double Mutant ◽  
Swine Influenza ◽  
Antigenic Drift ◽  
Amino Acid Substitutions ◽  
Wild Type ◽  
Antigenic Evolution ◽  
Ha Protein

ABSTRACTInfluenza A virus (IAV) of the H3 subtype is an important respiratory pathogen that affects both humans and swine. Vaccination to induce neutralizing antibodies against the surface glycoprotein hemagglutinin (HA) is the primary method used to control disease. However, due to antigenic drift, vaccine strains must be periodically updated. Six of the 7 positions previously identified in human seasonal H3 (positions 145, 155, 156, 158, 159, 189, and 193) were also indicated in swine H3 antigenic evolution. To experimentally test the effect on virus antigenicity of these 7 positions, substitutions were introduced into the HA of an isogenic swine lineage virus. We tested the antigenic effect of these introduced substitutions by using hemagglutination inhibition (HI) data with monovalent swine antisera and antigenic cartography to evaluate the antigenic phenotype of the mutant viruses. Combinations of substitutions within the antigenic motif caused significant changes in antigenicity. One virus mutant that varied at only two positions relative to the wild type had a >4-fold reduction in HI titers compared to homologous antisera. Potential changes in pathogenesis and transmission of the double mutant were evaluated in pigs. Although the double mutant had virus shedding titers and transmissibility comparable to those of the wild type, it caused a significantly lower percentage of lung lesions. Elucidating the antigenic effects of specific amino acid substitutions at these sites in swine H3 IAV has important implications for understanding IAV evolution within pigs as well as for improved vaccine development and control strategies in swine.IMPORTANCEA key component of influenza virus evolution is antigenic drift mediated by the accumulation of amino acid substitutions in the hemagglutinin (HA) protein, resulting in escape from prior immunity generated by natural infection or vaccination. Understanding which amino acid positions of the HA contribute to the ability of the virus to avoid prior immunity is important for understanding antigenic evolution and informs vaccine efficacy predictions based on the genetic sequence data from currently circulating strains. Following our previous work characterizing antigenic phenotypes of contemporary wild-type swine H3 influenza viruses, we experimentally validated that substitutions at 6 amino acid positions in the HA protein have major effects on antigenicity. An improved understanding of the antigenic diversity of swine influenza will facilitate a rational approach for selecting more effective vaccine components to control the circulation of influenza in pigs and reduce the potential for zoonotic viruses to emerge.

scholarly journals Substantial Antigenic Drift in the Hemagglutinin Protein of Swine Influenza A Viruses

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 248 ◽  
Author(s):  
Pia Ryt-Hansen ◽  
Anders Gorm Pedersen ◽  
Inge Larsen ◽  
Charlotte Sonne Kristensen ◽  
Jesper Schak Krog ◽  
...  
Keyword(s):  
Genetic Drift ◽  
Influenza A ◽  
Immune Escape ◽  
Swine Influenza ◽  
Antigenic Drift ◽  
Influenza A Viruses ◽  
Hemagglutinin Protein ◽  
One Year ◽  
High Level ◽  
Ha Protein

The degree of antigenic drift in swine influenza A viruses (swIAV) has historically been regarded as minimal compared to that of human influenza A virus strains. However, as surveillance activities on swIAV have increased, more isolates have been characterized, revealing a high level of genetic and antigenic differences even within the same swIAV lineage. The objective of this study was to investigate the level of genetic drift in one enzootically infected swine herd over one year. Nasal swabs were collected monthly from sows (n = 4) and piglets (n = 40) in the farrowing unit, and from weaners (n = 20) in the nursery. Virus from 1–4 animals were sequenced per month. Analyses of the sequences revealed that the hemagglutinin (HA) gene was the main target for genetic drift with a substitution rate of 7.6 × 10−3 substitutions/site/year and evidence of positive selection. The majority of the mutations occurred in the globular head of the HA protein and in antigenic sites. The phylogenetic tree of the HA sequences displayed a pectinate typology, where only a single lineage persists and forms the ancestor for subsequent lineages. This was most likely caused by repeated selection of a single immune-escape variant, which subsequently became the founder of the next wave of infections.

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