Lysosome-Associated Membrane Protein Targeting Strategy Improved Immunogenicity of Glycoprotein-Based DNA Vaccine for Hantaan virus

Background and Aims

Hemorrhagic fever with renal syndrome (HFRS) is a viral zoonotic disease primarily caused by the Hantaan virus (HTNV). This illness is prevalent in over 70 countries worldwide, posing a significant public health challenge due to its high endemicity. The glycoprotein (GP) of HTNV is a key structural protein that is crucial for triggering both humoral and cellular immune responses, making GP-specific immunoprophylaxis a promising therapeutic approach for HFRS.

Methods

Lysosome-associated membrane protein 1 (LAMP1) has the ability to target antigens to lysosomes and endosomes, thereby enhancing the immunogenicity of nucleic acid vaccines. In this study, we developed a recombinant DNA vaccine for HTNV GP that utilizes LAMP1 to direct the vaccine to the major histocompatibility complex (MHC) class II compartment. We conducted thorough computational analyses to evaluate the properties of the vaccine molecule and its potential immune responses in the body. Initial animal studies confirmed the effectiveness of GP-derived Th epitopes and multi-epitope vaccines.

Results

We designed two vaccines based on Gnc molecules and optimized them using a LAMP-targeting approach. Following three immunizations, mice receiving the pVAX-LAMP/Gnc vaccine exhibited increased splenocyte-specific IFN-γ secretion and higher serum antibody titers, particularly in terms of neutralizing activity. Furthermore, the efficacy of these molecular therapies was supported by preliminary in silico findings and laboratory animal experiments. By facilitating lysosomal trafficking and antigen presentation, the LAMP1 targeting strategy significantly enhanced both humoral and cellular immune responses specific to EBOV-GP.

Conclusions

Our research expands the strategic framework for improving DNA vaccine design and presents a promising candidate for HFRS prevention, establishing a foundation for future antiviral vaccine strategies.