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Pathogen vaccines and methods of producing and using the same

一种病原体、疫苗组合物的技术，应用在疫苗组合物领域，能够解决新型治疗策略疫苗未满足等问题，达到快速和方便制备、稳定性便携的效果

Active Publication Date: 2018-10-23
PRESIDENT & FELLOWS OF HARVARD COLLEGE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, there remains a continuing and unmet need for the development of novel therapeutic strategies and vaccines to treat infectious diseases

Method used

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  • Pathogen vaccines and methods of producing and using the same
  • Pathogen vaccines and methods of producing and using the same
  • Pathogen vaccines and methods of producing and using the same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0352] Example 1. Infection vaccine research

[0353] Preparation of FcMBL beads

[0354] Use magnetic FcMBL beads to capture pathogens or pathogen fragments, such as pathogen-associated molecular patterns (PAMPs). Briefly, 1 [mu]M streptavidin-coated superparamagnetic beads (Dynal, Life Technologies) were coupled to FcMBL. FcMBL is an engineered lectin consisting of the carbohydrate recognition domain (CRD) of mannose-binding lectin (MBL) fused to the Fc region of human IgG with engineered aminooxybiotin sites. The FcMBL fusion protein was localized on beads using aminooxybiotin on the end of the Fc region of FcMBL. Other beads have been tested for coupling to FcMBL and for capturing pathogens or pathogen fragments, such as 500nm Ademtech superparamagnetic beads. Direct coupling of FcMBL to streptavidin-free beads was also tested and shown to be useful for pathogen capture. The final concentration of beads used to generate the vaccine was 5 mg / mL.

[0355] Pathogen sampl...

Embodiment 2

[0414] Example 2. Mechanistic Analysis of Vaccine Compositions

[0415] Additional experiments were performed to determine the type of immune response involved in vaccine compositions (PLG or MPS scaffolds loaded with FcMBL-captured pathogens and adjuvants such as CpG / GM-CSF). Specifically, assays are performed to determine whether a vaccine composition of the invention mediates a cell-mediated response or an antibody-mediated response. In vaccinated animals, changes in levels of selected cytokines and levels of specific IgGs (eg, IgGl and IgG2a) in response to RS218 infection were measured. Significant changes in cytokine levels would indicate that the vaccine composition is acting primarily through a cell-mediated response, while significant changes in IgG levels would indicate an antibody-mediated response.

[0416] Histological studies are performed to determine whether the vaccine compositions of the invention are capable of eliciting a cell-mediated immune response agai...

Embodiment 3

[0418] Example 3. Vaccination protects against multiple pathogen infections

[0419] Vaccination protects mice against Mycobacterium tuberculosis infection

[0420] Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTb). TB usually affects the lungs, but it can also affect other parts of the body. Most TB infections have no symptoms; in this case, it is called latent TB. About 10% of latent infections progress to active disease, which, if left untreated, will kill about half of those infected. FcMBL binds to mannosylated components of the Mycobacterium tuberculosis (MTb) cell wall, such as mannose-capped lipoarabinomannan (ManLAM) and phosphatidylinositol mannoside (PIM) ( Figure 18 ).

[0421] To determine whether the vaccine composition of the present invention is useful against tuberculosis, mice were immunized with a single dose of an MPS-based vaccine composition containing GM-CSF / CpG and coated with mannose-capped arabic manna FcMBL b...

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Abstract

The present invention provides vaccine compositions and methods of producing such compositions. Other embodiments of the invention include methods of treating a pathogen infection, methods of vaccinating a subject against a pathogen infection, and methods for treating an antibiotic-resistance bacterial infection in a subject in need thereof. In further embodiments, the invention includes methods of decreasing the level of a pathogen in a subject having a pathogen infection, methods of increasing the surviving rate of a subject having a pathogen infection, methods of reducing the level of painassociated with a pathogen infection, and methods of reducing the level of distress associated with a pathogen infection in a subject in need thereof. Novel scaffold compositions and opsonin-bound orlectin-bound pathogen compositions, and uses thereof, are also provided herein.

Description

[0001] related application [0002] This application claims priority to U.S. Provisional Patent Application No. 62 / 343,448, filed May 31, 2016, and U.S. Provisional Patent Application No. 62 / 295,711, filed February 16, 2016, the entire contents of each of the foregoing applications Incorporated herein by reference. [0003] governmental support [0004] This invention was made with government support under DARPA N66001-11-1-4180. The government has certain rights in this invention. Background technique [0005] Infectious diseases are caused by pathogenic microorganisms (such as viruses, bacteria, fungi, etc.) that enter and multiply in living organisms. Common strategies to treat infectious diseases include administering antimicrobials, such as antivirals or antibiotics, to patients suffering from or susceptible to such infections, or using immunotherapies such as vaccination. [0006] However, in some cases, pathogenic microorganisms cannot be easily eradicated by usi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/00C07K14/435C07K14/47A61K48/00A61K8/00C12N9/00
CPCA61K39/385A61K45/06A61P31/00A61K2039/6031A61K2039/6087A61K2039/58A61K2039/6093A61K39/025A61K39/0258A61K2039/55522A61K2039/55561A61P31/06A61P31/04A61P31/10A61P31/18A61P33/02Y02A50/30
Inventor O·A-R·阿里M·J·卡特赖特E·多尔蒂A·格雷夫林D·E·因格贝尔D·J·穆尼B·塞尔乐A·斯塔弗德M·休珀D·怀特
Owner PRESIDENT & FELLOWS OF HARVARD COLLEGE
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