Positively Charged-Amylose-Entangled Au-Nanoparticles Acting as Protein Carriers and Potential Adjuvants to SARS-CoV-2 Subunit Vaccines

TheCOVID-19 pandemic continues to spread worldwide. To protectand control the spread of SARS-CoV-2, varieties of subunit vaccinesbased on spike (S) proteins have been approved for human applications.Here, we report a new subunit vaccine design strategy that functionsas both an antigen carrier and an adjuvant in immunization to elicithigh-level immune responses. The complex of 2-hydroxypropyl-trimethylammoniumchloride chitosan and amylose entangles Au nanoparticles (HTCC/amylose/AuNPs)forming 40 nm nanocarriers with a positive charge. The obtained positivelycharged nanoparticles reveal many merits, including the larger S proteinloading capacity in PBS buffer, higher cellular uptake ability, andlower cell cytotoxicity, supporting their potential as safe vaccinenanocarriers. Two functionalized nanoparticle subunit vaccines areprepared via loading full-length S proteins derived from SARS-CoV-2variants. In mice, both prepared vaccines elicit high specific IgGantibodies, neutralize antibodies, and immunoglobulin IgG1 and IgG2a.The prepared vaccines also elicit robust T- and B-cell immune responsesand increase CD19(+) B cells, CD11C(+) dendriticcells, and CD11B(+) macrophages at the alveoli and bronchiof the immunized mice. Furthermore, the results of skin safety testsand histological observation of organs indicated in vivo safety ofHTCC/amylose/AuNP-based vaccines. Summarily, our prepared HTCC/amylose/AuNPhave significant potential as general vaccine carriers for the deliveryof different antigens with potent immune stimulation.

Automated summary

This article introduces a new subunit vaccine design strategy that can serve as an antigen carrier and adjuvant to induce high-level immune responses, with the potential to be a safe vaccine nanocarrier.