Abstract
An effective tumor vaccine vector that can rapidly display neoantigens is urgently needed. Outer membrane vesicles (OMVs) can strongly activate the innate immune system and are qualified as immunoadjuvants. Here, we describe a versatile OMV-based vaccine platform to elicit a specific anti-tumor immune response via specifically presenting antigens onto OMV surface. We first display tumor antigens on the OMVs surface by fusing with ClyA protein, and then simplify the antigen display process by employing a Plug-and-Display system comprising the tag/catcher protein pairs. OMVs decorated with different protein catchers can simultaneously display multiple, distinct tumor antigens to elicit a synergistic antitumour immune response. In addition, the bioengineered OMVs loaded with different tumor antigens can abrogate lung melanoma metastasis and inhibit subcutaneous colorectal cancer growth. The ability of the bioengineered OMV-based platform to rapidly and simultaneously display antigens may facilitate the development of these agents for personalized tumour vaccines.
Highlights
1,2, Hao Qin[1,2], An effective tumor vaccine vector that can rapidly display neoantigens is urgently needed
Preclinical studies have shown that the recognition of tumor neoantigens by the immune system is a key event in the success of immunotherapy in oncology[6]
The immunogenicity of Outer membrane vesicles (OMVs) limits their use as natural nanoparticles for drug delivery, these same immunomodulatory characteristics, the capacity of the vesicles to accumulate in lymph nodes due to their small size and natural composition, and their ability to be manufactured in large quantities by bacterial fermentation, make OMVs attractive candidates as vaccine vectors
Summary
1,2, Hao Qin[1,2], An effective tumor vaccine vector that can rapidly display neoantigens is urgently needed. The immunogenicity of OMVs limits their use as natural nanoparticles for drug delivery, these same immunomodulatory characteristics, the capacity of the vesicles to accumulate in lymph nodes due to their small size and natural composition, and their ability to be manufactured in large quantities by bacterial fermentation, make OMVs attractive candidates as vaccine vectors This potential has already been realized to generate OMVbased vaccines against pathogenic microorganisms[19]. E. coli-derived OMVs expressing antigens from influenza virus, Plasmodium, Pneumococcus, Chlamydia, or Group A and B Streptococcus can stimulate the body to produce specific antibodies against these pathogenic microorganisms[22,23,24,25,26] These studies have demonstrated the great potential of OMVs as a vaccine platform that can stimulate humoral immunity. Constructing a functional OMVs platform that can rapidly display different tumor antigens and simultaneously display multiple tumor antigens are the keys to the development of personalized tumor vaccines
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