Key result
A multi-component repRNA vaccine formulated with LION induced EV-D68 antibody responses while reducing systemic inflammatory responses compared to LNP formulation in pigtail macaques.
Why the study?
Systemic inflammatory responses to lipid nanoparticle-formulated RNA vaccines may compromise safety and efficacy, highlighting the need to evaluate alternatives like cationic nanocarriers.
Does repRNA formulated with LION improve antigen-specific antibody responses and reduce systemic inflammation compared to LNP formulation in pigtail macaques?
Does repRNA formulated with LION improve antigen-specific antibody responses and reduce systemic inflammation compared to LNP formulation in pigtail macaques?
Formulating replicon RNA vaccines with LION rather than LNP reduces systemic inflammatory responses and preserves neutralizing antibody generation against complex antigens like EV-D68.
LION-formulated repRNA may localize innate responses to improve vaccine safety; leaves open human translation from primate data.
Replicon RNA (repRNA) vaccines are a transformative tool in combating infectious diseases, eliciting robust immune responses at lower doses. However, systemic inflammatory responses to lipid nanoparticle (LNP)-formulated RNA vaccines may compromise safety and efficacy. repRNA vaccines delivered with cationic nanocarriers like LION offer a promising alternative by localizing innate immune responses required to induce a robust adaptive response at the site of injection. Here, we show, in pigtail macaques, that a multi-component repRNA vaccine against two viral pathogens formulated with LION induces antigen-specific antibody (Ab) responses against enterovirus D68 (EV-D68) while reducing systemic inflammatory responses compared to the same vaccine formulated with LNP. Notably, early systemic interferon (IFN) levels inversely correlate with EV-D68 binding and neutralizing Ab titers, indicating that excessive systemic innate immune responses can impair RNA vaccine immunogenicity. These findings suggest that LION-mediated delivery offers a safer and more effective platform for RNA vaccines than conventional LNP formulations. By mitigating systemic cytokine induction, LION enhances vaccine immunogenicity and safety-key considerations for optimizing RNA vaccine design.
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Kimura et al. (2025) studied Enterovirus D68 (EV-D68) infection. Multi-component repRNA vaccine formulated with LION vs. Multi-component repRNA vaccine formulated with LNP was evaluated on Antigen-specific antibody responses against EV-D68 and systemic inflammatory responses. A multi-component repRNA vaccine formulated with LION induced EV-D68 antibody responses while reducing systemic inflammatory responses compared to LNP formulation in pigtail macaques.
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