Multiple tandem copies of conserved gp41 epitopes incorporated in gag virus-like particles elicit systemic and mucosal antibodies in an optimized heterologous vector delivery regimen

Jain, Sumiti; Patrick, Amy; Rosenthal, Kenneth L.

doi:10.1016/j.vaccine.2010.08.009

Cited by 28 publications

(21 citation statements)

References 70 publications

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“…DNA vaccines containing proper antigens can be designed to form VLPs in vivo, inducing strong cellular immune responses [263]. Multiple tandem copies of antigens can be incorporated in such a vector for enhanced immunogenicity [264].…”

Section: Virus-like Particles (Vlps)mentioning

confidence: 99%

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Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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Section: Virus-like Particles (Vlps)mentioning

confidence: 99%

“…Aluminum salts are often used with CpG ODNs to enhance and/or balance the immunogenicity of many different types of antigens [264,434,435]. Naloxone (an opioid receptor antagonist) has been recently evaluated with aluminum salts with use [436,437].…”

Section: Adjuvant Combinationsmentioning

confidence: 99%

Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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“…54). These include the generation of structurally stabilized peptides, scaffolds, or chimeras (55)(56)(57)(58)(59)(60)(61)(62)(63)(64); chimeric virus or virus-like particles by engrafting the MPER antibody epitopes onto other viruses (65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78); gp41 fusion proteins (79 -84); and liposomes containing MPER peptides (85). Different prime-boost strategies with peptides, DNA, and whole Env protein have also been explored in these studies.…”

mentioning

confidence: 99%

A Fusion Intermediate gp41 Immunogen Elicits Neutralizing Antibodies to HIV-1

Lai

Hock

Radzimanowski

et al. 2014

Journal of Biological Chemistry

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Background: HIV-1 gp41 MPER is a target for inducing broadly neutralizing antibodies. Results: Gp41 int folds into a compact elongated structure that induces neutralizing antibodies upon immunization. Conclusion: Presentation of gp41 int in a lipid environment is beneficial to induce neutralizing antibodies. Significance: Membrane-anchored gp41 int is a promising antigen to improve breadth and potency of anti-gp41 antibody responses.

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“…The second strategy explores the use of tandem repeats, which are ubiquitous in proteins, and form domains with extensive secondary structures including helices [39]. The use of this strategy has been restricted to present conformational proline-rich peptide to effect the necessary structure [40,41], or to simply increase immunogenicity [42][43][44].…”

Section: Introductionmentioning

confidence: 99%

Engineering of virus-like particles for alternative vaccine candidate targeting a hypervariable peptide antigen element

Anggraeni¹

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A promising alternative to replace the current egg-or cell culture-based technology for vaccine production from live viruses is virus-like particle (VLP) technology based on a microbial platform. VLPs are macromolecular assemblies of viral capsid proteins, which have been shown to tolerate insertion of antigen modules via genetic recombinant technology, yielding modular VLPs. Many studies on modular VLPs presume that when a peptide antigen element is taken out from the intact proteins and then modularised on VLPs, it is unable to fold into its native structure. However, until now, presentation of a peptide antigen element on a VLP and the impact of the display strategy to present the antigen element on the quality of the resulting antibodies (i.e. the ability of the antibodies to recognise the intact protein) are not fully understood. This thesis aims to understand the underlying fundamentals regarding modularisation of peptide antigen elements on VLPs for induction of high-quality antibodies. A hypervariable receptor-binding domain, Helix 190 (H190), from the hemagglutinin protein of influenza A virus was used as a model for modularisation on VLPs from murine polyomavirus (MuPyV) VP1 protein. Four major findings are presented. Firstly, two display strategies, i.e. arraying of H190 in tandem repeats and the use of helix promoter elements, were shown to display H190 in its immunogenic form equally. However, modularisation using tandem repeat display induced antibodies of a higher quality than modularisation using helix promoter elements.Secondly, the quality of antibodies induced by the tandem repeat display bearing two copies of H190 was optimum, thus no significant improvement was observed following the use of adjuvant or increasing the copy number of H190. Additionally, the increase in the copy number of H190 was shown to reduce the assembly capability and solubility of modular VP1 in an environment that was optimised for wild-type VP1. Thirdly, this thesis shows the novel finding in the use of flanking ionic elements to stabilise VLP precursors, termed as capsomeres, bearing two copies of H190 containing a hydrophobic stretch, which caused aggregation. Fourthly, the first steps towards obtaining the atomic crystal structure of presented H190 on a modular protein were performed, i.e. a mild and satisfactory laboratory process was developed to achieve high-purity modular VP1 capsomeres, unattainable using previously established expression and purification process of wild-type MuPyV VP1. This thesis shows a step forward towards understanding the presentation of a peptide antigen element on a VLP that enables induction of highquality antibodies, and towards VLP engineering to manipulate the aggregation and solubility of modular VP1. VLP technology based on a microbial platform presented here is iii a potentially safe and effective alternative vaccine candidate that targets a hypervariable peptide antigen element. The speed of the microbial platform allows a rapid response to the hypervariability of the pe...

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Multiple tandem copies of conserved gp41 epitopes incorporated in gag virus-like particles elicit systemic and mucosal antibodies in an optimized heterologous vector delivery regimen

Cited by 28 publications

References 70 publications

Selection of Adjuvants for Enhanced Vaccine Potency

Selection of Adjuvants for Enhanced Vaccine Potency

A Fusion Intermediate gp41 Immunogen Elicits Neutralizing Antibodies to HIV-1

Engineering of virus-like particles for alternative vaccine candidate targeting a hypervariable peptide antigen element

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