OligoDOMTM: a T-cell response-enhancing platform applied to cancer immunotherapy

BackgroundNeoepitopes derived (0) from tumors are attractive cancer immunotherapy targets, especially when combined with immune checkpoint inhibitors (CPIs). Vaccines using lipid nanoparticle (LNP)-encapsulated mRNA to deliver neoepitopes have shown encouraging results in patients and animal models, due to T cell-dependent responses. However, a low mutational burden is often a predictor of poor CPI response: the immune response against the few available mutations can be insufficient. An enhanced response to these few mutations could increase CPI efficacy. Here, we investigate the potential of oligoDOM™, a self-assembling sequence, to improve neoepitope immunogenicity and antitumor efficacy in murine cancer models.MethodsLNP-formulated mRNA constructs encoding short epitope strings fused with oligoDOM™ were tested. Immune responses in mice were compared between constructs with oligoDOM™ and their controls. Specific T-cell responses against four tumor models (MC38, CT26, TC-1, B16-OVA) were measured using ELISpot in naïve mice. Two models (TC-1 and B16-OVA) were further selected for tumor growth efficacy testing.ResultsLNP-formulated neoepitope-oligoDOM™ mRNA constructs induced a significantly superior immune response as compared with the control groups in four neoantigens tested. This increased specific immunogenicity is linked to antitumor growth effects in murine syngeneic cancer models such as the B16-OVA and TC-1. The induced T-cell immune response significantly correlated with tumor growth rate reduction.DiscussionCombining oligoDOM™ and LNP-mRNA technologies offers a versatile platform that allows for efficient short neoepitope strings delivery. This approach represents a feasible, potentially effective strategy for personalized cancer immunotherapy

OVX033, a nucleocapsid-based vaccine candidate, provides broad-spectrum protection against SARS-CoV-2 variants in a hamster challenge model

Spike-based COVID-19 vaccines induce potent neutralizing antibodies but their efficacy against SARS-CoV-2 variants decreases. OVX033 is a recombinant protein composed of the full-length nucleocapsid (N) protein of SARS-CoV-2 genetically fused to oligoDOM®, a self-assembling domain which improves antigen immunogenicity. OVX033 including N as an antigenic target is proposed as new vaccine candidate providing broad-spectrum protection against sarbecoviruses. OVX033 demonstrated its ability to trigger cross-reactive T cell responses and cross-protection against three variants of SARS-CoV-2 (B.1 Europe, Delta B.1.617.2, and Omicron B.1.1.529) in a hamster challenge model, as evidenced by lower weight loss, lower lung viral loads, and reduced lung histopathological lesions

Polysaccharides and Their Derivatives as Potential Antiviral Molecules

In the current context of the COVID-19 pandemic, it appears that our scientific resources and the medical community are not sufficiently developed to combat rapid viral spread all over the world. A number of viruses causing epidemics have already disseminated across the world in the last few years, such as the dengue or chinkungunya virus, the Ebola virus, and other coronavirus families such as Middle East respiratory syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV). The outbreaks of these infectious diseases have demonstrated the difficulty of treating an epidemic before the creation of vaccine. Different antiviral drugs already exist. However, several of them cause side effects or have lost their efficiency because of virus mutations. It is essential to develop new antiviral strategies, but ones that rely on more natural compounds to decrease the secondary effects. Polysaccharides, which have come to be known in recent years for their medicinal properties, including antiviral activities, are an excellent alternative. They are essential for the metabolism of plants, microorganisms, and animals, and are directly extractible. Polysaccharides have attracted more and more attention due to their therapeutic properties, low toxicity, and availability, and seem to be attractive candidates as antiviral drugs of tomorrow.</jats:p

Polysaccharides and Their Derivatives as Potential Antiviral Molecules

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