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vaccine for hsv-2

一种HSV-2UL19、HSV-2UL25的技术，应用在用于HSV-2的疫苗领域，能够解决不成功功效等问题

Active Publication Date: 2021-07-16
IMMUNE DESIGN CORP
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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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  • vaccine for hsv-2
  • vaccine for hsv-2

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0389] Increased CD4 T cell-based immunity against HSV-2 GD2 protein occurs when formulated with the adjuvant GLA-SE following multiple vaccinations in mice

[0390] 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.

[0391] 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...

Embodiment 2

[0393] GLA increases CD8 T cell responses in mice

[0394] 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.

[0395] 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 were identified as cells secreting any of the cytokines IFN-γ, IL-2, and TNF-α

[0396] like 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 i...

Embodiment 3

[0398] CD4 T cell-based immunogenicity against individual HSV-2 GD2, UL19 and UL25 proteins following multiple vaccinations in mice

[0399] 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

The present invention relates to the field of vaccines. The present invention provides a composition of recombinant HSV-2 protein and an agonist of the innate immune system such as an adjuvant as a vaccine. Proteins include envelope glycoproteins and structural proteins other than envelope glycoproteins, such as capsid proteins or envelope proteins. The vaccine is for HSV‑2 seropositive or seronegative subjects.

Description

technical field [0001] Vaccines for herpes simplex virus-2 infection and related methods and compositions. Background technique [0002] 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 is the leading cause of genital ulcers, which can appear as clusters of small, fluid-filled blisters that burst and form painful sores that take weeks to heal. Other symptoms may include fever, general malaise, muscle pain, painful urination, vaginal discharge, and swollen, painful lymph nodes in the groin area. Relapse is possible. The virus can reside in nerve cells throughout the life of an infected subject and reactivate from time to time, forming skin sores. Even in the absence of actual sores, virus can be produced and transmitted between individuals. It is currently incurable. [0003] Genital herpes...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/035C12N15/38A61K39/245A61P31/22
CPCA61K39/12A61K39/245C07K14/005G01N33/56994C12N2710/16622C12N2710/16634A61K38/00A61K2039/55572A61K2039/545A61P31/20A61P31/22A61P37/04
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 IMMUNE DESIGN CORP
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