Influenza vaccines based on virus-like particles

Kang, Sang-Moo; Song, June O.; Quan, Fu‐Shi; Compans, Richard W.

doi:10.1016/j.virusres.2009.04.005

Cited by 127 publications

(112 citation statements)

References 69 publications

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“…It has been shown that two viral envelope proteins (HA and NA) are required for budding of M1 from the cell, and the coexpression of HA and NA can efficiently incorporate M1 into extracellular VLPs (6,24,43). Knowing this to be the case, we asked whether coexpression of the M2 protein could independently promote M1 budding into VLPs without HA and NA proteins.…”

Section: Resultsmentioning

confidence: 99%

“…Despite these recent advances in the understanding of influenza A virus budding, little is known about the underlying mechanism of why the M1 protein is incapable of forming extracellular VLPs. This information is paramount for the resolution of the issue at hand: is there an intrinsic deficiency in the initiation of the M1 budding process, or are results simply dependent on the various expression systems used in each particular study (24,34)?…”

mentioning

confidence: 99%

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The Lack of an Inherent Membrane Targeting Signal Is Responsible for the Failure of the Matrix (M1) Protein of Influenza A Virus To Bud into Virus-Like Particles

Wang¹,

Harmon

Jin³

et al. 2010

J Virol

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The matrix protein (M1) of influenza A virus is generally viewed as a key orchestrator in the release of influenza virions from the plasma membrane during infection. In contrast to this model, recent studies have indicated that influenza virus requires expression of the envelope proteins for budding of intracellular M1 into virus particles. Here we explored the mechanisms that control M1 budding. Similarly to previous studies, we found that M1 by itself fails to form virus-like-particles (VLPs). We further demonstrated that M1, in the absence of other viral proteins, was preferentially targeted to the nucleus/perinuclear region rather than to the plasma membrane, where influenza virions bud. Remarkably, we showed that a 10-residue membrane targeting peptide from either the Fyn or Lck oncoprotein appended to M1 at the N terminus redirected M1 to the plasma membrane and allowed M1 particle budding without additional viral envelope proteins. To further identify a functional link between plasma membrane targeting and VLP formation, we took advantage of the fact that M1 can interact with M2, unless the cytoplasmic tail is absent. Notably, native M2 but not mutant M2 effectively targeted M1 to the plasma membrane and produced extracellular M1 VLPs. Our results suggest that influenza virus M1 may not possess an inherent membrane targeting signal. Thus, the lack of efficient plasma membrane targeting is responsible for the failure of M1 in budding. This study highlights the fact that interactions of M1 with viral envelope proteins are essential to direct M1 to the plasma membrane for influenza virus particle release.The late phase of the influenza A virus replication cycle is marked by the occurrence of assembly and budding at the plasma membrane of infected cells, which leads to the separation of virion and host cell membranes and ultimately results in the production of infectious virus particles. This critical step is a highly concerted process driven largely by protein-protein, protein-lipid, and protein-nucleic acid interactions (34, 40). It has been established for many years that four viral structural components, namely, the matrix protein (M1), hemagglutinin (HA), neuraminidase (NA), and M2, are actively involved in the assembly and budding process (34,35,40), although the identities of these inter-and intramolecular interactions and regulatory mechanisms for influenza A virus assembly and budding are unclear. It has also been suggested that interactions of M1 with various cytoplasmic tails (CTs) of HA, NA, and M2 are critical to drive the assembly and release of influenza A virions from the surface of infected cells (1,5,10,18,25,29,30,68). To date, these interactions have been largely speculative because direct interactions have been demonstrated only for M1 and M2 (5, 18, 29).Early investigations into the budding machinery of influenza A virus using vaccinia virus-and baculovirus-based expression systems indicated that M1 was the only viral protein absolutely required for the assembly of virus particles (14,15...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

The Lack of an Inherent Membrane Targeting Signal Is Responsible for the Failure of the Matrix (M1) Protein of Influenza A Virus To Bud into Virus-Like Particles

Wang¹,

Harmon

Jin³

et al. 2010

J Virol

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“…VLPs are structurally very similar to their correspondent pathogenic virus, and therefore, they are able to induce CD4+ cell proliferation which results in B-cell as well as in cytotoxic T-cell immune responses [10,11]. The market entry of GlaxoSmithKline's human papilloma virus vaccine (Cervarix™) finally demonstrated the immunological potency of insect cell derived VLP vaccines [12].…”

Section: Introductionmentioning

confidence: 99%

Trichoplusia ni cells (High FiveTM) are highly efficient for the production of influenza A virus-like particles: a comparison of two insect cell lines as production platforms for influenza vaccines

et al. 2010

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Virus-like particles (VLPs) consisting of the influenza A virus proteins haemagglutinin (HA) and matrix protein (M1) represent a new alternative approach for vaccine design against influenza virus. Influenza VLPs can be fast and easily produced in sufficient amounts in insect cells using the baculovirus expression system. Up to now, influenza VLPs have been produced in the Spodoptera frugiperda cell line Sf9. We compared VLP production in terms of yield and quality in two insect cell lines, namely Sf9 and the Trichoplusia ni cell line BTI-TN5B1-4 (High Five™). Additionally we compared VLP production with three different HAs and two different M1s from influenza H1 and H3 strains including one swine-origin pandemic H1N1 strain. Comparison of the two cell lines showed dramatic differences in baculovirus background as well as in yield and

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“…HA and NA) of the virus. These changes on the new subtype prevent the efficiency of the matched antibodies against the parental subtypes [10,11]. These variations cause the viral scape from the host immune system.…”

Section: Introductionmentioning

confidence: 99%

Cloning, expression and purification of hemagglutinin conserved domain (HA2) of influenza A virus, to be used in broad-spectrum subunit vaccine cocktails

Farahmand

Akbari

Kh.

et al. 2016

vacres

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Introduction: Influenza virus has several conserved peptides which have the capacity to be used as suitable candidates for appropriate and stable vaccine production against different types of influenza viruses. One of these peptides is HA2, the hemagglutinin stalk domain which mediates the membrane fusion and is conserved amongst different sub-types of influenza virus. This peptide is a good candidate for participation in vaccine structure to induce immunity and antibody production. The ensued antibody may hamper the membrane fusion and subsequently the virus propagation. Methods: The peptide sequence of HA2 from influenza virus A/Tehran/18/2010 (H1N1) was analyzed using in silico tools in order to evaluate its physicochemical properties and identification of its best immunogenic sites. The confirmed sequence was amplified and cloned into a pET28a vector and the recombinant protein was over-expressed prokaryotically and confirmed by Western blotting. Results: The bioinformatics data showed that HA2 peptide stability and immunogenicity. The generated HA2 construct was confirmed by PCR, endonuclease restriction enzyme analysis and sequencing. The expression of HA2 was confirmed by SDS-PAGE and Western blot analysis. The results on the cell lysate demonstrated the high expression of HA2 subunit of the influenza virus hemagglutinin. Conclusion: One of the disadvantages of the current flu vaccines is that they cannot produce efficient broad-spectrum cellular and humoral immune responses against all subtypes of the virus due to the genetic variation of the virus. Therefore, such a conserved protein is potentially a good candidate for production of a broad-spectrum vaccine to prevent influenza epidemics and pandemics.

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Influenza vaccines based on virus-like particles

Cited by 127 publications

References 69 publications

The Lack of an Inherent Membrane Targeting Signal Is Responsible for the Failure of the Matrix (M1) Protein of Influenza A Virus To Bud into Virus-Like Particles

The Lack of an Inherent Membrane Targeting Signal Is Responsible for the Failure of the Matrix (M1) Protein of Influenza A Virus To Bud into Virus-Like Particles

Trichoplusia ni cells (High FiveTM) are highly efficient for the production of influenza A virus-like particles: a comparison of two insect cell lines as production platforms for influenza vaccines

Cloning, expression and purification of hemagglutinin conserved domain (HA2) of influenza A virus, to be used in broad-spectrum subunit vaccine cocktails

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