Реферат
Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic.
Реферат
The invention and application of vaccines have made tremendous contributions to fight against pandemics for human beings. However, current vaccines still have shortcomings such as insufficient cellular immunity, the lack of cross-protection, and the risk of antibody-dependent enhancement (ADE). Thus, the prevention and control of pandemic viruses including Ebola Virus, human immunodeficiency virus (HIV), Influenza A viruses, Zika, and current SARS-CoV-2 are still extremely challenging. Nanoparticles with unique physical, chemical, and biological properties, hold promising potentials for the development of ideal vaccines against these viral infections. Moreover, the approval of the first nanoparticle-based mRNA vaccine BNT162b has established historic milestones that greatly inspired the clinical translation of nanovaccines. Given the safety and extensive application of subunit vaccines, and the rapid rise of mRNA vaccines, this review mainly focuses on these two vaccine strategies and provides an overview of the nanoparticle-based vaccine delivery platforms to tackle the current and next global health challenges. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.
Реферат
Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic. Graphical By engineering capsid of AAV vector and designing a sequence encoding trimeric RBD fused with a biological adjuvant, AAV-based vaccines successfully induce fast, balanced and endurable humoral and cellular immune responses, thus serving as potential candidates for next generation vaccinesImage 1