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Vaccination with poxvirus vectors by mechanical disruption of the epidermis

A mechanical destruction, pox virus technology, applied in the direction of virus/phage, virus, antiviral agent, etc., can solve the problem of ineffective production of CMI, etc.

Inactive Publication Date: 2011-12-14
创雷克斯公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Non-live vaccines have generally been shown to be ineffective in producing CMI
Furthermore, although live vaccines may induce CMI, some live attenuated vaccines cause disease in immunosuppressed individuals

Method used

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  • Vaccination with poxvirus vectors by mechanical disruption of the epidermis
  • Vaccination with poxvirus vectors by mechanical disruption of the epidermis
  • Vaccination with poxvirus vectors by mechanical disruption of the epidermis

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0196] Example 1: Epidermal VV immunization via skin scarification will produce significantly stronger cellular and humoral immunity than the conventional injection route.

[0197] Generate VV skin scratch method mouse model. The acute epidermal pox response in scratched mice is very similar to that of the human smallpox vaccine. Using this model, a rigorous comparison of primary and memory adaptive immunity following vaccinia virus (VV) immunization by skin scarification (s.s.), subcutaneous (s.c), intradermal (i.d.) and intramuscular (i.m.) injection answer. The highly immunogenic intraperitoneal (i.p.) route of injection, although not used in clinical immunization, was included as a positive control for VV-specific immune responses. Compared with conventional injection routes (s.c, i.d., and i.m.), VV skin scarification induced significantly stronger primary and memory T cell responses, as well as higher serum VV-specific IgG levels (Fig. 1). Long-term T cell memory and ...

example 2

[0198] Example 2: VV skin scratch method provides excellent protection against secondary antigen challenge.

[0199] This example uses three different models to determine whether VV skin scarification provides superior protection against secondary challenge. The first challenge model was cutaneous poxvirus infection (transcutaneous infection). This model was chosen for two reasons. First, the protective efficacy of smallpox vaccine candidates was evaluated clinically by challenging vaccinated individuals with Dryvax skin scarification. Second, natural poxvirus infection can be acquired through exposure of the skin, especially damaged skin areas, to the virus. Following skin challenge, skin viral load was determined using VV-specific real-time PCR ( figure 2 ). Mice immunized with s.c, i.d., and i.m. injections all showed partial protection, showing 15, 9.5, and 3-fold reductions in viral load, respectively, compared to unimmunized control mice. In i.p. immunized mice, a ...

example 3

[0202] Example 3: VV skin scratch-associated protection against secondary challenge requires memory T cells but not Ab.

[0203] To investigate the mechanisms underlying the superior protective efficacy following poxvirus skin scarification, the relative contributions of humoral and cellular responses in skin scarification-associated immune protection will be investigated. Wild-type (wt) and B cell-deficient μMT mice were immunized with VV via skin scarification or i.p. injection, the two most immunogenic routes in this study. Subsequently, memory mice were challenged by secondary skin or intranasal poxvirus infection. As shown in Figure 5a, i.p. immunized μMT mice had a 4-log higher viral load than i.p. immunized wild-type mice when challenged with VV on the skin. Interestingly, μMT mice immunized via the s.s. route still showed strong protection against skin challenge, with viral loads comparable to wild-type mice immunized via skin scarification. However, when T cells wer...

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Abstract

The present invention provides methods of stimulating an immune response to an antigen in an individual comprising administering to an individual in need thereof a live, modified and / or recombinant replication-attenuated or non-replicating poxvirus comprising sufficient to stimulate the An immune responsive amount of antigen wherein the virus is administered by mechanical disruption of the epidermis. The present invention also provides a kit comprising said virus and an epidermis disrupting device.

Description

[0001] Federally Supported Research [0002] The present invention is based on the grant number U19 AI057330 and 5U54AI057159-05 granted by the National Institute of Allergy and Infectious Diseases (National Institute of Allergy and Infectious Diseases, NIAID) of the National Institutes of Health (NIH). carried out with the support of. The US Government has certain rights in this invention. Background technique [0003] Traditionally, vaccines consist of live attenuated pathogens, inactivated whole organisms, or inactivated toxins. In many cases, these approaches have succeeded in inducing immune protection based on antibody-mediated responses. However, certain pathogens, such as HIV, HCV, TB, Plasmodium, and cancer, require the induction of cell-mediated immunity (CMI). Non-live vaccines have generally been shown to be ineffective in producing CMI. Furthermore, although live vaccines may induce CMI, some live attenuated vaccines cause disease in immunosuppressed individu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/275A61P35/00A61P33/02A61P37/00
CPCA61K2039/5256A61K2039/54C12N2799/023A61K39/00A61P31/04A61P31/10A61P31/12A61P33/02A61P35/00A61P37/00A61P37/04Y02A50/30
Inventor T·S·顾巴刘露铮
Owner 创雷克斯公司
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