Recently, the research group led by Prof. ZHAO Xiao, CHENG Keman and NIE Guangjun from the National Center for Nanoscience and Technology (NCNST) have achieved dual precise regulation of vaccine carrier structure and surface antigen arrangement, and successfully constructed an efficient, safe and long-acting intranasal respiratory syncytial virus (RSV) nanovaccine. The results have been published in Nature Materials.

While protein structure-based vaccine design has facilitated the clinical application of injectable RSV subunit vaccines targeting pre-F antigens, developing an effective intranasal RSV vaccine remains challenging. The geometric properties and surface antigen patterns of vaccines are key determinants for robust B cell activation in the respiratory tract. Yet, no feasible strategy allows systematic tuning of these parameters for the rational design of intranasal vaccines.

Here, researchers report a library of DNA nanocarriers with controlled dimensions and sizes, aiming to systemically evaluate the influence of geometric properties on intranasal retention. Taking advantage of the precise control on DNA nanocarriers and antigen functionalization, they organized the surface antigen patterns of pre-F monomers on DNA nanocarriers to maximize B cell activation. The optimized DNA nanocarrier-based vaccine elicited comparable humoral immunity in mice to that of the clinically approved trimeric mRNA vaccine against RSV, but with greater durability. While intramuscular mRNA vaccines failed to induce effective respiratory mucosal immunity, the intranasal DNA nanocarrier-based vaccine achieved robust local and systemic immune activation, conferring potent protection against RSV infection.

This rational design of intranasal RSV vaccines is expected to be a general strategy for testing and advancing potent intranasal vaccines for a range of respiratory diseases.

Figure 1. Precision-Designed Intranasal RSV Vaccine Based on DNA Nanocarriers.

Contact:

Prof. ZHAO Xiao

National Center for Nanoscience and Technology (NCNST)

E-mail: zhaox@nanoctr.cn