Novel microparticulate Zika vaccine induces a significant immune response in a preclinical murine model after intramuscular administration

新型微粒寨卡疫苗在肌肉注射后在临床前小鼠模型中诱导出显著的免疫反应

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作者:Akanksha Kale, Devyani Joshi, Ipshita Menon, Priyal Bagwe, Smital Patil, Sharon Vijayanand, Keegan Braz Gomes, Martin D'Souza

Abstract

Despite the detrimental effects associated with Zika infection, there are no approved treatments or vaccines available. To address the need for a safe and effective vaccine for Zika, we formulated poly(lactic-co-glycolic) acid (PLGA) polymeric vaccine microparticles (MP) encapsulating the inactivated Zika virus, along with adjuvant MP encapsulating Alhydrogel® and MPL-A®. We characterized the vaccine MP for size, surface charge, morphology, encapsulation efficiency, and antigen integrity. Further, we evaluated immunogenicity and cytotoxicity of vaccine MP in vitro in murine dendritic cells. Vaccine MP with adjuvants induced significantly higher production of nitric oxide, a marker of innate immunity, when compared to the untreated cells. In addition, vaccine MP with or without adjuvants induced increased autophagy in murine dendritic cells when compared to inactivated Zika virus, which is critical in antigen presentation. Next, we evaluated in vivo efficacy of vaccine MP with and without adjuvants in a preclinical murine model by measuring the immune response after intramuscular administration. Vaccine MP with adjuvants induced significant IgG, Ig2a, and IgG1 titers as compared to the control group of untreated mice. Thus, this study provided the 'proof-of-concept' for a microparticulate Zika vaccine.

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