Influenza virus-like particle can accommodate multiple subtypes of hemagglutinin and protect from multiple influenza types and subtypes

Pushko, Peter; Pearce, Melissa B.; Ahmad, Attiya; Tretyakova, Irina; Smith, Gale; Belser, Jessica A.; Tumpey, Terrence M.

doi:10.1016/j.vaccine.2011.06.068

Cited by 75 publications

(99 citation statements)

References 37 publications

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“…Pushko et al recently constructed multitypic VLPs incorporating 3 different subtypes. Both the pandemic-subtype VLP (incorporating H5N1, H7N2, and H2N3) and seasonal VLP (incorporating circulating strains) induced neutralizing antibodies and protected ferrets from lethal challenge (141). VLPs based on non-influenza virus proteins but incorporating influenza virus peptides have also been developed (142).…”

Section: Virus-like Particlesmentioning

confidence: 99%

Traditional and New Influenza Vaccines

2013

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SUMMARY The challenges in successful vaccination against influenza using conventional approaches lie in their variable efficacy in different age populations, the antigenic variability of the circulating virus, and the production and manufacturing limitations to ensure safe, timely, and adequate supply of vaccine. The conventional influenza vaccine platform is based on stimulating immunity against the major neutralizing antibody target, hemagglutinin (HA), by virus attenuation or inactivation. Improvements to this conventional system have focused primarily on improving production and immunogenicity. Cell culture, reverse genetics, and baculovirus expression technology allow for safe and scalable production, while adjuvants, dose variation, and alternate routes of delivery aim to improve vaccine immunogenicity. Fundamentally different approaches that are currently under development hope to signal new generations of influenza vaccines. Such approaches target nonvariable regions of antigenic proteins, with the idea of stimulating cross-protective antibodies and thus creating a “universal” influenza vaccine. While such approaches have obvious benefits, there are many hurdles yet to clear. Here, we discuss the process and challenges of the current influenza vaccine platform as well as new approaches that are being investigated based on the same antigenic target and newer technologies based on different antigenic targets.

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Section: Virus-like Particlesmentioning

confidence: 99%

Traditional and New Influenza Vaccines

2013

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“…Such VLPs are expected to be able to activate B-cells capable of producing broadly neutralizing influenza antibodies [47,48]. VLPs expressing multiple HA molecules (H2, H5, H7 or H1, H3 and B) on the same particle have been produced and shown to be immunogenic [50], and the presentation of multiple molecules on a single particle will be highly cost-effective. These VLPs are, however, not expected to fully exploit epitope dilution as the antigens are from different (sub)types and therefore extremely different and the limited number of components included (3) may not be sufficient for adequate dilution of strain-specific epitopes.…”

Section: Edip For Soluble Versus Particulate Antigensmentioning

confidence: 99%

EDiP: the Epitope Dilution Phenomenon. Lessons learnt from a malaria vaccine antigen and its applicability to polymorphic antigens

Kusi

Faber

Koopman

et al. 2017

Expert Review of Vaccines

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Introduction: Polymorphism in vaccine antigens poses major challenges to vaccinologists. The Plasmodium falciparum Apical Membrane Antigen 1 (AMA1) poses such a challenge. We found that immunization with a mixture of three variants yielded functional antibody levels to all variants comparable to levels induced by monovalent immunization. The mechanism behind the observed broadening was shown to be an increase in the fraction of cross-reactive antibodies, most likely because strain-specific epitopes are present at lower frequency relative to conserved epitopes. Areas covered: We hereby introduce the Epitope Dilution Phenomenon (EDiP) as a practical strategy for the induction of broad, cross-variant antibody responses against polymorphic antigens and discuss the utility and applicability of this phenomenon for the development of vaccines against polymorphic antigens of pathogens like Influenza, HIV, Dengue and Plasmodium. Expert commentary: EDiP can be used to broaden antibody responses by immunizing with a mixture of at least 3 antigenic variants, where the variants included can differ, yet yield broadened responses. ARTICLE HISTORY

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“…A novel influenza VLP platform containing HA subtypes derived from three distinct strains has also been reported [70]. This recombinant VLP design resulted in the expression of three HA subtypes co-localized within a VLP (fig.…”

Section: Complex Vlps Derived From Enveloped Virusesmentioning

confidence: 99%

“…Experimental triple-HA VLPs containing HA proteins derived from seasonal H1N1, H3N2, and type B influenza viruses were immunogenic and protected ferrets from challenge with all three seasonal viruses. Similarly, VLPs containing HA subtypes derived from H5N1, H7N2, and H2N2 viruses protected ferrets from three potentially pandemic influenza viruses [70]. This technology may represent a novel strategy for the rapid development of trivalent seasonal and pandemic influenza vaccines.…”

Section: Complex Vlps Derived From Enveloped Virusesmentioning

confidence: 99%

Development of Virus-Like Particle Technology from Small Highly Symmetric to Large Complex Virus-Like Particle Structures

2013

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Virus-like particle (VLP) technology is a promising approach for the construction of novel vaccines, diagnostic tools, and gene therapy vectors. Initially, VLPs were primarily derived from non-enveloped icosahedral or helical viruses and proved to be viable vaccine candidates due to their effective presentation of epitopes in a native conformation. VLP technology has also been used to prepare chimeric VLPs decorated with genetically fused or chemically coupled epitope stretches selected from immunologically defined target proteins. However, structural constraints associated with the rigid geometrical architecture of icosahedral or helical VLPs pose challenges for the expression and presentation of large epitopes. Complex VLPs derived from non-symmetric enveloped viruses are increasingly being used to incorporate large epitopes and even full-length foreign proteins. Pleomorphic VLPs derived from influenza or other enveloped viruses can accommodate multiple full-length and/or chimeric proteins that can be rationally designed for multifunctional purposes, including multivalent vaccines. Therefore, a second generation of VLP carriers is represented by complex particles reconstructed from natural or chimeric structural proteins derived from complex enveloped viruses. Further development of safe and efficient VLP nanotechnology may require a rational combination of both approaches.

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Influenza virus-like particle can accommodate multiple subtypes of hemagglutinin and protect from multiple influenza types and subtypes

Cited by 75 publications

References 37 publications

Traditional and New Influenza Vaccines

Traditional and New Influenza Vaccines

EDiP: the Epitope Dilution Phenomenon. Lessons learnt from a malaria vaccine antigen and its applicability to polymorphic antigens

Development of Virus-Like Particle Technology from Small Highly Symmetric to Large Complex Virus-Like Particle Structures

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