posted on 2021-11-04, 18:36authored byShuang Li, Bo Wang, Shun Jiang, Yi Pan, Yuhua Shi, Wei Kong, Yaming Shan
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.