Comparative immunogenicity evaluations of influenza A virus M2 peptide as recombinant virus like particle or conjugate vaccines in mice and monkeys

Vaccine ◽  
2009 ◽  
Vol 27 (9) ◽  
pp. 1440-1447 ◽  
Author(s):  
Tong-Ming Fu ◽  
Karen M. Grimm ◽  
Michael P. Citron ◽  
Daniel C. Freed ◽  
Jiang Fan ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Recombinant Virus ◽  
Influenza A ◽  
Conjugate Vaccines ◽  
Virus Like Particle

scholarly journals Inhibition of the Ubiquitin-Proteasome System Affects Influenza A Virus Infection at a Postfusion Step

2010 ◽  
Vol 84 (18) ◽  
pp. 9625-9631 ◽  
Author(s):  
Ivy Widjaja ◽  
Erik de Vries ◽  
Donna M. Tscherne ◽  
Adolfo García-Sastre ◽  
Peter J. M. Rottier ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Rna Synthesis ◽  
Proteasome Inhibitors ◽  
Ubiquitin Proteasome System ◽  
Bafilomycin A1 ◽  
Virus Like Particle ◽  
Viral Particles ◽  
Removal Experiments ◽  
Ubiquitin Proteasome

ABSTRACT We have demonstrated that influenza A virus (IAV) RNA synthesis depends on the ubiquitin-proteasome system. IAV replication was reduced both by proteasome inhibitors and in E36ts20 cells, which contain the thermolabile ubiquitin-activating enzyme E1. While virus entry was not affected in E36ts20 cells, the proteasome inhibitor MG132 retained viral particles in the cytoplasm. Addition-removal experiments of MG132 in combination with bafilomycin A1, a well-established inhibitor of IAV entry and fusion, showed that MG132 affected IAV infection at a postfusion step. This was confirmed by the lack of inhibition of IAV entry by proteasome inhibitors in a virus-like particle fusion assay.

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 A virus-like particle vaccine candidate for influenza A virus based on multiple conserved antigens presented on hepatitis B tandem core particles

Vaccine ◽  
2018 ◽  
Vol 36 (6) ◽  
pp. 873-880 ◽  
Author(s):  
Alejandro Ramirez ◽  
Stephen Morris ◽  
Sophie Maucourant ◽  
Isabella D'Ascanio ◽  
Vincenzo Crescente ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Influenza A Virus ◽  
Influenza A ◽  
Vaccine Candidate ◽  
Virus Like Particle ◽  
Core Particles

scholarly journals A functional RNA structure in the influenza A virus ribonucleoprotein complex for segment bundling

2020 ◽  
Author(s):  
Naoki Takizawa ◽  
Koichi Higashi ◽  
Risa Karakida Kawaguchi ◽  
Yasuhiro Gotoh ◽  
Yutaka Suzuki ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Influenza A Virus ◽  
Rna Structure ◽  
Recombinant Virus ◽  
Influenza A ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Virus Genome ◽  
Pseudoknot Structure ◽  
Functional Rna

AbstractThe influenza A virus genome is segmented into eight viral RNAs (vRNA). Intersegment interactions are necessary for segment bundling, and secondary structures on vRNA are assumed to be involved in the process. However, the RNA structure required for segment bundling remains unidentified because the secondary structure of vRNA in virion was partially unwound by binding viral non-specific RNA binding proteins. Here, we revealed the global intersegment interactions and the secondary structure of the vRNA in virion. We demonstrated that a pseudoknot structure was formed on a segment in the virion and the impairment of replication and packaging of the other specific segment was observed in cells infected with recombinant virus which had mutations in the pseudoknot structure. Moreover, we showed that the intersegment interactions were reconstituted in the recombinant virus. Our data provides the first evidence that the functional RNA structure on the influenza A virus genome affects segment bundling.

scholarly journals Tetherin Sensitivity of Influenza A Viruses Is Strain Specific: Role of Hemagglutinin and Neuraminidase

2015 ◽  
Vol 89 (18) ◽  
pp. 9178-9188 ◽  
Author(s):  
Kerstin Gnirß ◽  
Pawel Zmora ◽  
Paulina Blazejewska ◽  
Michael Winkler ◽  
Anika Lins ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Particle System ◽  
Influenza A Viruses ◽  
Virus Like Particle ◽  
Viral Hemagglutinin ◽  
Dependent Inactivation ◽  
Tetherin Expression ◽  
Infected Cells ◽  
Tetherin Antagonism

ABSTRACTThe expression of the antiviral host cell factor tetherin is induced by interferon and can inhibit the release of enveloped viruses from infected cells. The Vpu protein of HIV-1 antagonizes the antiviral activity of tetherin, and tetherin antagonists with Vpu-like activity have been identified in other viruses. In contrast, it is incompletely understood whether tetherin inhibits influenza A virus (FLUAV) release and whether FLUAV encodes tetherin antagonists. Here, we show that release of several laboratory-adapted FLUAV strains and a seasonal FLUAV strain is inhibited by tetherin, while pandemic FLUAV A/Hamburg/4/2009 is resistant. Studies with a virus-like particle system and analysis of reassortant viruses provided evidence that the viral hemagglutinin (HA) is an important determinant of tetherin antagonism but requires the presence of its cognate neuraminidase (NA) to inhibit tetherin. Finally, tetherin antagonism by FLUAV was dependent on the virion context, since retrovirus release from tetherin-positive cells was not rescued, and correlated with an HA- and NA-dependent reduction in tetherin expression. In sum, our study identifies HA and NA proteins of certain pandemic FLUAV as tetherin antagonists, which has important implications for understanding FLUAV pathogenesis.IMPORTANCEInfluenza A virus (FLUAV) infection is responsible for substantial global morbidity and mortality, and understanding how the virus evades the immune defenses of the host may uncover novel targets for antiviral intervention. Tetherin is an antiviral effector molecule of the innate immune system which can contribute to control of viral invasion. However, it has been unclear whether FLUAV is inhibited by tetherin and whether these viruses encode tetherin-antagonizing proteins. Our observation that several pandemic FLUAV strains can counteract tetherin via their HA and NA proteins identifies these proteins as novel tetherin antagonists and indicates that HA/NA-dependent inactivation of innate defenses may contribute to the efficient spread of pandemic FLUAV.

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