Mymetics Corp (MYMX)

[Work Harder]

Therefore, the Th2-promoting effects of Alum and its ability to boost B-cell responses in a Th2-driven manner may be potentially dangerous in vaccines for the treatment of allergic diseases.

Interestingly, licensed products do not contain liposomes but virosomes. Virosomes are spherical lipid vesicles (without viral DNA/RNA) that carry the influenza glycoproteins hemagglutinin and neuraminidase on their surface

Novel adjuvants for immunotherapies also include TLR9 ligands such as CpG as it was shown that CpG oligodeoxynucleotides (ODN) can shift Th2 to Th1 responses. Accordingly, CpG induces the secretion of the Th1 cytokines IL-1, IFN-a, TNF-a, and IL-12. Thus, a phase II study with a ragweed allergen conjugated to CpG (TLR9 ligand) demonstrated reduced symptoms of allergic rhinitis in patients during ragweed season (Marshall et al. 2001). Besides TLR ligands, other immunologically active substances are used as adjuvants. Those include cytokines, bacterial toxins, and glycolipids (Reed et al. 2009).

The next step to more efficiently leverage the immune-modulating properties of the applied adjuvants is to combine adjuvant and antigen into a single molecule. Compared to a non-conjugated mixture of allergen and adjuvant, such allergen:adjuvant fusion proteins have some key advantages (also summarized in Fig. 1): (1) they efficiently target the antigen to the relevant immune cells in vivo (usually APCs) by binding to receptors specific for the used adjuvant. (2) Once they have reached their target cells, such constructs simultaneously co-deliver both antigen and adjuvant to the same cell in a fixed molecular ratio, resulting in reproducible levels of immune system activation and a reduced risk of potentially detrimental bystander activation. (3) Binding of the adjuvant part of the allergen:adjuvant fusion protein was repeatedly shown to not only trigger immune cell activation but also uptake of the respective fusion proteins. Under these conditions, uptake of the fused antigen always takes place in the context of the adjuvant-mediated immune cell activation, resulting in both qualitative and quantitative differences in processing and presentation of the fused antigen

Because of the resulting ability to administer lower doses of the respective fusion proteins, allergen:adjuvant fusion proteins have the potential to increase both safety and efficacy compared to the mixture of both components. Accordingly, allergen:adjuvant fusion proteins were repeatedly shown to strongly increase the immunogenicity of the fused antigen, resulting in the efficient induction of protective immune responses against the fused antigen (Kastenmüller et al. 2011; Schülke et al. 2011; Song et al. 2015). Technically, such allergen:adjuvant fusion proteins are generated either by recombinant DNA technologies (if the fused adjuvant is a protein) or chemical conjugation using different chemical linker groups (e.g., for immune-stimulating CpG motifs and TLR4 ligands).

In the following part of the review, the published strategies employing allergen:adjuvant fusion proteins will be described grouped according to the used adjuvant classes (for an overview of all strategies, see Fig. 2 and Table 1).

Kitzmüller et al. (2018) recently described the enhanced immunogenicity, reduced allergenicity, and intrinsic adjuvanticity of flagellin C:Bet v 1 fusion proteins in human monocyte-derived DCs and T cells from allergic patients. They fused a truncated version of the Salmonella flagellin C to either the N- or C-terminus of the major birch pollen allergen Bet v 1 (Kitzmüller et al. 2018). In immunological tests, both fusion proteins efficiently matured human monocyte-derived DCs (upregulation of CD80, CD83, and CD86) in a TLR5-dependent manner while showing reduced IgE-binding capacity (Kitzmüller et al. 2018). Moreover, both fusion proteins displayed an enhanced T-cell stimulatory capacity, resulting in retained T-cell proliferation and increased secretion of IL-13 and IFN-? compared to Bet v 1 alone (Kitzmüller et al. 2018).

& more

CpG

https://link.springer.com/article/10.1007/s00005-019-00551-8

Paul-Ehrlich-Institut

https://www.pei.de/EN/service/faq/faq-coronavirus-content.html

https://www.dynavax.com/science/cpg-1018/

The data are being further analysed and evaluated by the European Medicines Agency (EMA).

https://www.pei.de/EN/newsroom/hp-news/2021/210315-pei-informs-temporary-suspension-vaccination-astra-zeneca.html

https://www.pei.de/EN/newsroom/hp-news/hp-news-node.html;jsessionid=496315B0CBFE2D2FFC3B4BB9D4069F06.intranet241

& Anergis liquidation w/ new headquarters

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