Lipid-based vaccine nanoparticles for induction of humoral immune responses against HIV-1 and SARS-CoV-2

JOURNAL OF CONTROLLED RELEASE

卷:330

Article

Park, Kyung Soo^1,2  Bazzill, Joseph D.^2,3  Son, Sejin^2,3  Nam, Jutaek^2,3  Shin, Seung Won⁴  Ochyl, Lukasz J.^2,3  Stuckey, Jeanne A.^5,6  Meagher, Jennifer L.⁵  Chang, Louise⁵  Song, Jun⁷  Montefiori, David C.⁸  LaBranche, Celia C.⁸  Smith, Janet L.^5,6  Xu, Jie⁷  Moon, James J.^1,2,3 

[1] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Biointerfaces Inst, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA

[4] Sungkyunkwan Univ, Sch Chem Engn, Suwon, Gyeonggi Do, South Korea

[5] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA

[6] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA

[7] Univ Michigan, Sch Med, Med Ctr, Ctr Adv Models Translat Sci & Therapeut, Ann Arbor, MI 48019 USA

[8] Duke Univ, Sch Med, Dept Surg, Durham, NC 27710 USA

关键词: COVID-19;    SARS-CoV-2;    HIV;    Vaccine;    Nanoparticle;   

DOI  :  10.1016/j.jconrel.2020.12.031

来源: Elsevier

【 摘 要 】

The current health crisis of corona virus disease 2019 (COVID-19) highlights the urgent need for vaccine systems that can generate potent and protective immune responses. Protein vaccines are safe, but conventional approaches for protein-based vaccines often fail to elicit potent and long-lasting immune responses. Nanoparticle vaccines designed to co-deliver protein antigens and adjuvants can promote their delivery to antigen-presenting cells and improve immunogenicity. However, it remains challenging to develop vaccine nanoparticles that can preserve and present conformational epitopes of protein antigens for induction of neutralizing antibody responses. Here, we have designed a new lipid-based nanoparticle vaccine platform (NVP) that presents viral proteins (HIV-1 and SARS-CoV-2 antigens) in a conformational manner for induction of antigen-specific antibody responses. We show that NVP was readily taken up by dendritic cells (DCs) and promoted DC maturation and antigen presentation. NVP loaded with BG505.SOSIP.664 (SOSIP) or SARS-CoV-2 receptor-binding domain (RBD) was readily recognized by neutralizing antibodies, indicating the conformational display of antigens on the surfaces of NVP. Rabbits immunized with SOSIP-NVP elicited strong neutralizing antibody responses against HIV-1. Furthermore, mice immunized with RBD-NVP induced robust and long-lasting antibody responses against RBD from SARS-CoV-2. These results suggest that NVP is a promising platform technology for vaccination against infectious pathogens.

【 授权许可】

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