{"id":193,"date":"2023-03-02T07:01:31","date_gmt":"2023-03-02T07:01:31","guid":{"rendered":"https:\/\/mrna.creative-biolabs.com\/blog\/?p=193"},"modified":"2023-03-02T07:01:31","modified_gmt":"2023-03-02T07:01:31","slug":"manganese-based-lnp-mrna-vaccine-has-strong-immunogenicity","status":"publish","type":"post","link":"https:\/\/mrna.creative-biolabs.com\/blog\/manganese-based-lnp-mrna-vaccine-has-strong-immunogenicity\/","title":{"rendered":"Manganese-Based LNP-mRNA Vaccine Has Strong Immunogenicity"},"content":{"rendered":"

A variety of vaccines have been approved to prevent COVID-19, including two mRNA vaccines, Comirnty (BNT162b2) developed by Pfizer \/ BioNTech and Spikevax (mRNA-1273) developed by Moderna. The mRNA vaccine has played an extremely effective role in fighting against the COVID-19 pandemic due to its unique advantages such as high immunogenicity, rapid production, and low cost.<\/span><\/p>\n

However, the immune escape of an endless stream of SARS-CoV-2 mutants, such as the current major epidemic strain Omicron, poses a major challenge to the existing mRNA vaccines. Therefore, it is imperative to develop a more effective mRNA vaccine<\/a> <\/strong><\/span>against the new COVID-19 mutants.<\/span><\/p>\n

Efficient antigen presentation of antigen presenting cells (APCs), such as dendritic cells (DCs), is a prerequisite for mRNA vaccines to function efficiently, which requires sufficient protein translation and APCs maturation. In addition, the high expression of costimulatory molecules on mature DC provides a secondary signal for the activation of immature T cells. Adjuvants can promote DC maturation and up-regulate the expression of DC costimulatory molecules. Therefore, the co-delivery of adjuvants is an effective strategy to enhance the immune effect of the mRNA vaccine.<\/span><\/p>\n

Recently, Song Yong\u2019s team, from the State Key Laboratory of Biotherapy in West China Hospital of Sichuan University, published a research paper entitled “Manganese-Coordinated mRNA Vaccines With Enhanced mRNA Expression and Immunogenicity Induce Robust Immune Responses Against SARS-CoV-2 Variants” in Science Advances<\/em>, the sub-journal of Science<\/em>.<\/span><\/p>\n

Based on a new ionizable lipid (IC8) and introducing manganese (2-valent Mn ion), an agonist of stimulator of interferon genes (STING), a new mRNA delivery system IC8\/Mn-LNP with high immunogenicity was constructed. It was confirmed for the first time that Mn can not only promote the maturation of antigen-presenting cells (APC) by activating the STING pathway, but also increase the expression of mRNA by promoting lysosome escape.<\/span><\/p>\n

In this study, IC8\/Mn-LNP was also used to deliver the mRNA sequence of the full-length spike protein of COVID-19 mutant Delta or Omicron. Both mRNA vaccines had a large number of specific IgG responses to Delta or Omicron, strong neutralization ability to new coronavirus, Th1 cell biased immune response, and good safety.<\/span><\/p>\n

This study shows that IC8\/Mn-LNP, a new mRNA delivery system, has great potential in the development of Mn co-enhanced mRNA vaccines with strong immunogenicity and good safety.<\/span><\/p>\n

Co-delivery of adjuvants is an effective strategy to enhance the immune effect of the mRNA vaccine. Agonists of Toll-like receptors (TLRs) and stimulators of interferon genes (STING) have been utilized as adjuvants in mRNA vaccines. However, TLR agonists can cause severe cytokine storms, which limits their clinical application. Also, STING agonists used as adjuvants can induce relatively low levels of local and systemic inflammation.<\/span><\/p>\n

In September 2019, Miao Lei et al. published a paper in the journal Nature Biotechnology<\/em> and developed an ionizable lipid library as an mRNA delivery carrier to promote mRNA delivery<\/a><\/strong><\/span> in vivo<\/em> and enhance the anti-tumor effect by activating the STING pathway.<\/span><\/p>\n

Manganese (Mn) is an essential element in many physiological processes, which can stimulate the STING pathway by directly activating cGAS, but it is unclear whether Mn enhances the immune effect of the mRNA vaccine.<\/span><\/p>\n

The delivery system can protect mRNA from rapid degradation and help it to be absorbed and released by cells, which is essential for the efficient expression of mRNA in vivo<\/em>. Lipid nanoparticles<\/span><\/a><\/strong> (LNP) have shown good efficacy and safety in the only two approved mRNA COVID-19 vaccines.<\/span><\/p>\n

In July 2022, a research paper published by Song Yong’s team in the journal Advanced Functional Materials<\/em> found that the ionizable lipids in LNP could significantly affect the expression of mRNA. Compared with the ionizable lipids with single nitrogen atoms used in the LNP of Moderna’s mRNA vaccine, the ionizable lipids with multiple tertiary amino nitrogen atoms could significantly enhance the immunogenicity of the mRNA vaccine and trigger a strong and lasting humoral immune response.<\/span><\/p>\n

In the latest study published in Science Advances<\/em>, Song Yong’s team designed and constructed a new type of lipid nanoparticle containing manganese (Mn) and novel ionizable lipids (IC8)-IC8\/Mn-LNP.<\/span><\/p>\n

The team used IC8\/Mn-LNP to deliver mRNA and then evaluated its immunogenicity and its protective mechanism against the SARS-CoV-2 mutant after loading mRNA (IC8\/Mn@S) encoding the full-length spike protein (S protein) of the SARS-CoV-2 mutant.<\/span><\/p>\n

Manganese (Mn) increases the expression of mRNA by promoting lysosome escape and stimulates the maturation of antigen presenting cells (APCs) by activating the STING pathway. In addition, IC8\/Mn@S induces strong and persistent IgG antibodies against COVID-19 mutants Delta and Omicron at the optimal dose (Mn:mRNA=1:1).<\/span><\/p>\n

This study shows that IC8\/Mn-LNP, a new mRNA delivery system, has great potential in the development of Mn co-enhanced mRNA vaccine with strong immunogenicity and good safety, which has a good prospect of clinical application.<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

A variety of vaccines have been approved to prevent COVID-19, including two mRNA vaccines, Comirnty (BNT162b2) developed by Pfizer \/ BioNTech and Spikevax (mRNA-1273) developed by Moderna. The mRNA vaccine has playedRead More…<\/a><\/p>\n","protected":false},"author":1,"featured_media":194,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[33,7],"_links":{"self":[{"href":"https:\/\/mrna.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/posts\/193"}],"collection":[{"href":"https:\/\/mrna.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/mrna.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/mrna.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/mrna.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/comments?post=193"}],"version-history":[{"count":2,"href":"https:\/\/mrna.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/posts\/193\/revisions"}],"predecessor-version":[{"id":196,"href":"https:\/\/mrna.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/posts\/193\/revisions\/196"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/mrna.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/media\/194"}],"wp:attachment":[{"href":"https:\/\/mrna.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/media?parent=193"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/mrna.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/categories?post=193"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/mrna.creative-biolabs.com\/blog\/wp-json\/wp\/v2\/tags?post=193"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}