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Human respiratory syncytial virus (HRSV) virus-like particles (VLPS) based vaccine

A syncytial virus, virus-like technology, applied in the direction of viruses, viral peptides, antiviral agents, etc., can solve problems such as ineffective vaccines

Active Publication Date: 2018-07-31
TECHNOVAX
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

On the other hand, vaccines attenuated with stronger levels of virus were found to be ineffective

Method used

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  • Human respiratory syncytial virus (HRSV) virus-like particles (VLPS) based vaccine
  • Human respiratory syncytial virus (HRSV) virus-like particles (VLPS) based vaccine
  • Human respiratory syncytial virus (HRSV) virus-like particles (VLPS) based vaccine

Examples

Experimental program
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Effect test

Embodiment 1

[0152] Embodiment 1: the production of pneumonia virus VLP

[0153] Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants and children and represents a significant health burden in the elderly and the globally immunocompromised. Despite decades of research effort, there is still no licensed vaccine available for RSV.

[0154] We developed a virus-like particle (VLP)-based RSV vaccine, which consists of human metapneumovirus matrix protein (hMPV M) as the structural backbone and RSV fusion glycoprotein (F) in a pre- or post-fusion conformation as its main surface immunogen Assembled. The vaccine consists of the prefusion F protein, the postfusion F protein, or a combination of these two conformations, and is adjuvanted with a squalene-based oil emulsion. Immunization with these VLP vaccines provided comprehensive protection against RSV infection, preventing detectable viral replication in the lungs of mice following challenge. Analysis o...

Embodiment 2

[0183] Example 2: Development of Recombinant RSV F Showing Fusion and Prefusion Conformations

[0184] Structural analysis of the fused F protein showed that the C-terminus of F2 was located in the relative direction of and away from the N-terminus of F1 ( Figure 1B ), whereas in the prefusion conformation these domains are adjacent (9, 13). We identified several neighboring amino acids within this domain that are less than 10 Angstroms apart. Based on this analysis, we generated nine recombinant constructs with different disulfide bonds between these domains to stabilize the F protein in its prefusion conformation, as well as constructs with mutations in the furin cleavage site (Fig. 7 ).

[0185] Prefusion F VLPs were produced in mammalian cells and analyzed by dot blot analysis with Palivizumab (antigenic site II) to determine F protein expression and dot blot analysis with 5C4 mAb to determine the antigenic site presence and stability (Figure 7). We assessed the post...

Embodiment 3

[0187] Embodiment 3: display the VLP of RSV F fusion post or fusion pre-conformation

[0188] The RSV envelope displays three virus-encoded membrane-anchored proteins, the F, G and SH proteins (19). Matrix (M) proteins beneath the envelope multimerize during morphogenesis and delineate virion assembly and budding (20). To assemble VLPs, we employed pre- or post-fusion RSV F and as a backbone human metapneumovirus (hMPV) matrix protein (M), which we found to be more efficient than RSV M in VLP formation. To optimize the interaction of RSV F and hMPV M, we replaced the cytoplasmic tail of the RSV F protein with an analogous domain of the hMPV F protein, based on the recruitment of RSV F and incorporation into VLPs confirmed by yield analysis compared to unmodified F surface enhancements ( Figure 1C ).

[0189] Analysis of purified VLPs by Western blot revealed that RSV F hybrids co-purify with hMPV M ( Figure 2B ), and replacing the cytoplasmic tail facilitated the incorpo...

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Abstract

Described herein are virus-like particles (VLPs) that display on their surfaces antigenic paramyxovirus (e.g., RSV and / or MPV) proteins. Also described are methods of making and using these VLPs.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Application No. 62 / 212,306, filed August 31, 2015, the contents of which are incorporated herein by reference in their entirety. [0003] Statement Regarding Federally Funded Research [0004] This invention was made in part with one or more grants from the National Institute of Health. The United States Government may have certain rights in this invention. technical field [0005] The present invention relates to compositions comprising human respiratory syncytial virus (hRSV) virus-like particles (VLPs), methods of making and using these hRSV VLPs, including the production and production of hRSV VLP-based vaccines. In particular, the present disclosure includes strategies and methods for the development of novel VLP-based vaccine systems that protect humans against infection by different hRSV serotypes (A and B). Also described herein are methods of producing VLP ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/12A61K39/155A61P31/14C07K14/08C07K14/115C07K14/135
CPCC12N2760/18323C12N2760/18334C12N2760/18534C12N2760/18571A61K39/12A61P31/14C12N2760/18523
Inventor J·M·加拉尔萨V·西米卡H·博伊加德
Owner TECHNOVAX
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