Surface-Functionalized Silica-Coated Calcium Phosphate Nanoparticles Efficiently Deliver DNA-Based HIV-1 Trimeric Envelope Vaccines against HIV-1

Human immunodeficiency virus type 1 (HIV-1) infection remains one of the worst crises in global health. The prevention of HIV-1 infection is a crucial task that needs to be addressed due to the absence of a licensed vaccine against HIV-1. DNA vaccines present a promising alternative approach to combat HIV-1 infection due to their excellent safety profile, lack of severe side effects, and relatively rapid fabrication. Traditional vaccines composed of a monomeric envelope or peptide fragments have been indicated to lack protective efficacy mediated by inducing HIV-1-specific neutralizing antibodies in clinical trials. The immunogenicity and protection against HIV-1 induced by DNA vaccines are limited due to the poor uptake of these vaccines by antigen-presenting cells and their ready degradation by DNases and lysosomes. To address these issues of naked DNA vaccines, we described the feasibility of CpG-functionalized silica-coated calcium phosphate nanoparticles (SCPs) for efficiently delivering DNA-based HIV-1 trimeric envelope vaccines against HIV-1. Vaccines comprising the soluble BG505 SOSIP.664 trimer fused to the GCN4-based isoleucine zipper or bacteriophage T4 fibritin foldon motif with excellent simulation of the native HIV-1 envelope were chosen as trimer-based vaccine platforms. Our results showed that SCP-based DNA immunization could significantly induce both broad humoral immune responses and potent cellular immune responses compared to naked DNA vaccination in vivo. To the best of our knowledge, this study is the first to assess the feasibility of CpG-functionalized SCPs for efficiently delivering DNA vaccines expressing a native-like HIV-1 trimer. These CpG-functionalized SCPs for delivering DNA-based HIV-1 trimeric envelope vaccines may lead to the development of promising vaccine candidates against HIV-1.