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Vaccines for HSV-2

A HSV-2, immunogenic technology, applied in the direction of medical preparations containing active ingredients, allergic diseases, peptide sources, etc., can solve problems such as unsuccessful efficacy

Active Publication Date: 2015-03-11
免疫设计公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Conventional and historic vaccine types including whole virus, inactivated virus, attenuated live virus, modified live virus, and cell culture-derived subunits have been largely unsuccessful or of low efficacy (Stanberry, Herpes 11(suppl 3) 161A-169A, 2004)

Method used

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  • Vaccines for HSV-2
  • Vaccines for HSV-2
  • Vaccines for HSV-2

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0393] Increased CD4 T cell-based immunity against HSV-2 GD2 protein occurs when formulated with the adjuvant GLA-SE after multiple vaccinations in mice

[0394] In this example, the ability of GLA-SE to increase CD4 T cell responses following immunization of mice with a recombinant protein vaccine was assessed.

[0395] 0.8, 4 or 20 μg in combination with 0.8, 4 or 20 μg GLA-SE (SE percentage was 2% in this study and all subsequent studies), SE alone or PBS delivered intramuscularly in 100 μl (50 μl per leg) Five Balb / c mice in each group were immunized with recombinant gD protein via a prime / boost immunization protocol (d0 prime / d21 boost). Mice immunized with GLA-SE, SE alone or PBS in the absence of recombinant protein served as negative controls. On day 4 post-boost, by using gD 272-285 Antigen-specific splenic CD4 T cell responses were measured by intracellular cytokine staining (ICS) for IFN-γ, TNF-α, and IL-2 following ex vivo restimulation of splenocyte cultures wit...

Embodiment 2

[0397] GLA increases CD8 T cell responses in mice

[0398] In this example, the ability of GLA-SE to increase CD8 T cell responses following immunization of mice with a recombinant protein vaccine was assessed.

[0399] Ovalbumin was used as a model protein. Female C57Bl / 6 mice were injected s.c. with ovalbumin encoding lentivirus ( image 3 and 4 "LV-OVA" in ) and on day 21 by i.m. injection of recombinant ovalbumin adjuvant with various doses of GLA-SE ( image 3 and 4"OVA+GLA / SE") in the Four days later, splenic T-cell responses to the following in vitro stimulators were measured by intracellular cytokine staining (ICS): antibodies to OVA MHC class I peptides 55-62 and 257-264 and MHC class II peptides 323-339 or CD3 and CD28 . CD8 T cells are defined as cells that secrete any of the cytokines IFN-γ, IL-2, and TNF-α

[0400] Such as image 3 As shown in , there was a higher percentage of CD8 T cells in mice that received an antigen boost, with the highest percentage...

Embodiment 3

[0402] CD4 T cell-based immunogenicity against individual HSV-2 GD2, UL19 and UL25 proteins following multiple vaccinations in mice

[0403] The goal of this set of studies was to identify a single mouse strain in which CD4 T cell-based immunogenicity against each protein subunit in the vaccine could be assessed. To this end, a series of experiments were performed in mice to identify d ), C57BL / 6(H-2 b ) and CB6F1 (H-2 d +2 b ))) individual CD4 T cell epitopes within each HSV-2 antigen (ie gD2, UL19 and UL25). The experimental strategy consisted of intramuscular immunization of uninfected mice in 100 μl (50 μl per leg) with 5 μg of each recombinant protein formulated together with 5 μg GLA-SE as monovalent immunogen within the context of a prime / boost immunization protocol (d0 prime / d21 boost). rat composition. Antigen-specific CD4 T cell responses were analyzed on day 4 post-boost using 15-mer peptide libraries whose sequences were derived from the corresponding amino ac...

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Abstract

Compositions of recombinant HSV-2 proteins and an agonist of the innate immune system, such as an adjuvant, are provided as a vaccine. Proteins include an envelope glycoprotein and a structural protein other than an envelope glycoprotein, e.g., a capsid or tegument protein. The vaccine is for use in either HSV-2 seropositive or seronegative subjects.

Description

[0001] Cross References to Related Applications [0002] This application claims U.S. Provisional Patent Application Nos. 61 / 647,764 (filed May 16, 2012), 61 / 679,387 (filed August 3, 2012) and 61 / 714 under 35 U.S.C. § 119(e) , 158 (filed October 15, 2012), all of which are incorporated herein by reference in their entirety. [0003] Reference Sequence Listing [0004] The sequence listing of this patent application is provided separately under the file name "47733_SeqListing.txt". The content of this document (which was formed on May 16, 2013 and consists of 45,969 bytes) is incorporated in its entirety. technical field [0005] Vaccines for herpes simplex virus-2 infection and related methods and compositions. Background technique [0006] HSV-2 (herpes simplex virus-2) is a member of the herpesviridae family, a group of DNA viruses that tend to cause skin lesions (such as chickenpox and febrile herpes) and are characterized by latent and recurrent infections . HSV-2 i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/569C07K14/005A61K38/00
CPCC12N2710/16634C07K14/005A61K39/245A61K38/00C12N2710/16622A61K39/12G01N33/56994A61K2039/55572A61K2039/545A61P31/20A61P31/22A61P37/04
Inventor 小托马士·W.·杜宾斯基南西·A.·胡思肯史考特·H.·罗宾斯玛格莉特·D.·莫瑞
Owner 免疫设计公司
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