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Vaccine for use in prophylaxis and/or treatment of disease

A technology for vaccines and diseases, applied in the field of vaccines, can solve problems such as

Pending Publication Date: 2020-09-04
盈珀治疗有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Furthermore, in situ synthesis of virus-like particles has been used before [Luo et al. (2003); Sohji et al. (2011); Andersson et al. (2016); Andersson & Holst (2016); Andersson et al. system, for HIV Env and malaria antigens, but not for ERVEnv displaying ISD mutations on in situ synthesized VLPs

Method used

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  • Vaccine for use in prophylaxis and/or treatment of disease
  • Vaccine for use in prophylaxis and/or treatment of disease
  • Vaccine for use in prophylaxis and/or treatment of disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0359] Mutations in the vaccine-encoded immunosuppressive domain (ISD)

[0360] As an improved first strategy, two point mutations were introduced in the sequence of MelARV Env to inactivate the immunosuppressive domain (ISD) ( image 3 ). These specific mutations were previously tested and analyzed for murine leukemia virus by Schlecht-Louf et al. (Schlecht-Louf, G. et al., Retroviral infection in vivo requires an immune escape virus factor encrypted in the envelope protein of oncoretroviruses. Proc Natl Acad Sci U S A, 2010. 107(8): pp. 3782-7). The virus encoding this modified form of MelARV Env is called Ad5-MelARV-ISD.

[0361] Effect of Ad5-MelARV-ISD on antibody responses in CD1 mice

[0362] Outbred CD1 mice were primed with DNA-MelARV or DNA-MelARV-ISD and subsequently boosted with AD5-MelARV or Ad5-MelARV-ISD according to vaccination timeline IV. Four weeks after adenovirus vaccination, blood samples were collected and analyzed by ELISA.

[0363] like Fi...

Embodiment 2

[0367] Effect of Ad5-MelARV-ISD on antibody response and metastasis in C57BL / 6 mice

[0368]C57BL / 6 mice were vaccinated and challenged according to vaccination timeline III. Mice received DNA-MelARV or DNA-MelARV-ISD followed by the corresponding adenovirus. Analysis of antibody responses revealed that MelARV-ISD slightly increased the level of B16F10-GP cell-specific antibodies ( Figure 8A ). However, this increase was not significant and was only slightly above background in PBS-vaccinated mice. Such as Figure 8B As shown in , no effect was observed for antibodies specific for p15E. Corresponding to tumor cell-bound antibodies, metastasis was slightly, but not significantly, reduced in MelARV-ISD vaccinated mice ( Figure 8C )

Embodiment 3

[0370] Effect of Ad5-MelARV-ISD on T cell responses in Balb / C mice

[0371] In addition to antibody responses, the effect of Ad5-MelARV-ISD on T cell priming and activation was also analyzed. ELISPOT ( Figure 9 ) and ICS (Fig. 10) both showed increased levels of AH1-specific T cells in Ad5-MelARV-ISD vaccinated mice compared to Ad5-MelARV. As observed by ICS, double positive IFNγ compared with the native form + TNFα + CD8 + T cells were significantly increased in Ad5-MelARV-ISD vaccinated mice. IFNγ + The integrated geometric mean (IGM) of the cells also showed significant differences from native Ad5-MelARV. The IGM combines the number of positive cells with the mean fluorescence intensity and thus also takes into account the quality of activated immune cells. The IGM of TNFa remained insignificant (data not shown).

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Abstract

The present invention relates to an adenoviral vector capable of encoding a virus-like particle (VLP), the VLP displaying an inactive immune-suppressive domain (ISD). The vaccine of the invention shows an improved immune response from either of both of the response pathways initiated by CD4 T cells or CD8 T cells.

Description

technical field [0001] The present disclosure relates to vaccines for use in the prevention and / or treatment of disease. It is worth noting that the disease can be derived from endogenous retroviruses, ie, cancer, for example. The vaccines of the present invention particularly relate to viruses capable of forming virus-like particles in eukaryotic cells. In certain embodiments of the invention, virus-encoded virus-like particles (VE-VLPs) are produced in a patient in order to develop an immunogenic response to endogenous retroviruses. [0002] Background of the invention [0003] It was observed more than a century ago that the development of cancer is closely linked to the immune system, and it is now well established that the immune system provides long-term protection against emerging cancers. Malignant cells, on the other hand, develop strategies to evade immune surveillance and unleash their lethal potential. [0004] Although immune cells are able to detect and kill ...

Claims

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Application Information

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IPC IPC(8): C07K14/005C07K14/47
CPCC07K14/005C07K14/47C07K14/4713A61K39/21A61P35/00C12N2740/10034C12N2710/10043C12N2740/10023C12N2710/24123C12N2710/24134A61K2039/5258A61K39/235C12N7/00A61K2039/525C12N15/86A61P35/04A61K2039/545A61K2039/585C12N2740/10022C12N2740/10071
Inventor P.霍尔斯特C.蒂里翁L.诺伊基尔希
Owner 盈珀治疗有限公司
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