Liposomal group A streptococcus vaccine

A group A streptococcus and lipid vesicle technology, applied in the field of liposome group A streptococcus vaccine, can solve the problem that immunity is not optimal

Pending Publication Date: 2017-05-03
GRIFFITH UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, systemic vaccination is not an optimal route for inducing immunity against GAS

Method used

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  • Liposomal group A streptococcus vaccine
  • Liposomal group A streptococcus vaccine
  • Liposomal group A streptococcus vaccine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0132] foreword

[0133]Group A Streptococcus (GAS) mainly infects the human upper respiratory tract (URT) mucous membrane and skin, causing many diseases. Infection can lead to toxic shock syndrome, necrotizing fasciitis, and myositis. The incidence of necrotizing fasciitis is 1 in 100,000, and the mortality rate is as high as 70% (1). Post-streptococcal diseases—rheumatic fever (RF) and rheumatic heart disease (RHD)—are also of concern. There are approximately 15.6 million active cases of RHD and almost 400,000 deaths each year (2). Pharyngitis was the most common disease following bacterial colonization of URT, whereas RF and RHD were strongly associated with untreated major infections of the pharynx (3). GAS infection and its associated diseases are prevalent in native populations in tropical regions, developing and developed countries, causing 500,000 deaths per year (4), underscoring the urgent need for a vaccine.

[0134] GAS vaccine candidates can be divided into M...

Embodiment 2

[0185] The following experiments were performed to investigate the effect of liposome size on immunogenicity.

[0186] Liposome extrusion was accomplished with a thermal block using a 1 mL syringe mini-extruder (Avanti Polar Lipids). The rehydrated solution was passed through 50 nm, 400 nm, 1000 mm filters (Avanti Polar Lipids) 11 times with the thermal block set at ~40°C. Liposome size measurements were performed by Nanosizer (Dynamic Light Scattering or DLS).

[0187] Such as Figure 12 As shown, J8-Lipo-DT can be extruded to form nano- or micron-sized particles. The majority of particle sizes have a narrow molecular weight distribution (low polydispersity index Figure 13The data showed that J8-Lipo-DT size did not affect the systemic IgG response. However, if Figure 14 As shown, liposomes of larger size induced J8-specific mucosal responses.

Embodiment 3

[0189] The following experiments were performed to investigate the effect of freeze-drying of liposomes on immunogenicity. Liposome films were rehydrated with milliQ water containing 10% trehalose and then lyophilized. 1, 4 and 7 weeks after lyophilization, J8-Lipo-DT powder was reconstituted with PBS.

[0190] Figure 15 Size results of liposome size measurements by Nanosizer (Dynamic Light Scattering or DLS) are shown. The majority of particle sizes have a narrow molecular weight distribution (low polydispersity index Figure 16 It was shown that reconstituted lyophilized J8-Lipo-DT liposomes induced J8-specific systemic responses without the need for additional adjuvants. This is a comparable immune response to freshly prepared J8-Lipo-DT. Trehalose is important for the immunogenicity of lyophilized J8-Lipo-DT. Figure 17 showed that reconstituted lyophilized J8-Lipo-DT liposomes induced J8-specific mucosal responses.

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Abstract

An immunogenic agent suitable for preventing, treating or immunizing against one or a plurality of different pathogen comprises an immunogenic agent which comprises one or a plurality of pathogen-derived proteins, fragments, variants or derivatives thereof displayed on a lipid vesicle and a carrier protein such as diptheria toxoid located in an intravesicular space. The immunogenic agent may be suitable for intranasal administration and may be capable of eliciting a mucosal immune response. The immunogenic agent may further comprise an activator of innate immunity such as trehalose-6,6'-dibehenate and / or a bile salt such as sodium deoxycholate. The one or plurality of pathogens may be group A streptococcus, viruses or hookworms.

Description

[0001] field of invention [0002] The present invention relates to the prevention and treatment of diseases and conditions caused by or associated with Group A Streptococcus bacteria. More specifically, the present invention relates to liposomal vaccines for the treatment or prevention of diseases and disorders caused by Group A Streptococcus bacteria by inducing a mucosal immune response. [0003] Background of the invention [0004] Group A Streptococcus (GAS) primarily infects the human upper respiratory tract (URT) mucosa as well as the skin, causing a wide range of diseases. Infection can lead to toxic shock syndrome, necrotizing fasciitis, and myositis. Necrotizing fasciitis affects 1 in 100,000 and is fatal in up to 70% of cases (1). Diseases following streptococcal infection - rheumatic fever (RF) and rheumatic heart disease (RHD) - are also of high concern. There are an estimated 15.6 million RHD epidemics and approximately 400,000 deaths each year (2). The most c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/09A61K39/385A61K9/127A61P31/04
CPCA61K9/127A61K39/09A61K39/385A61K2039/55583A61K2039/6037A61K2039/543A61K39/092A61K39/12A61K9/0043A61K9/19A61K2039/55555A61K2039/55572A61K2039/6062A61K2039/62A61K2039/70C12N2760/16134C12N2760/16234A61P31/04
Inventor 迈克尔·戈德麦福思·扎曼
Owner GRIFFITH UNIVERSITY
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