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Human Metapneumovirus G Protein Immunogenicity and Safety Explored via Carrier Protein Fusion
Tian Ren1,2, Kailun Ma2, Xinmiao Lai2
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
Abstract:
Human metapneumovirus (HPMV) is a significant pathogen that causes lower respiratory tract infections. Given the weak immunogenicity thereof, and the few relevant studies, the utility of the viral membrane protein G as a vaccine remains controversial. In this study, the G extracellular domain (RMG) of HMPV was expressed either alone or fused with the cholera toxin B subunit (CTB) and "cross-reacting material 197" (CRM197) carrier proteins (giving G-CTB/G and CRM197), to enhance immunogenicity. The non-glycosylated G protein (REG) expressed in Escherichia coli served as a control. SDS-PAGE and anti-His tag Western blotting verified that each protein was successfully expressed and correctly identified. BALB/c mice were immunized with each protein and subjected to challenge with HMPV. The results showed that, although immunization with RMG alone failed to induce potent neutralizing antibodies, it modestly reduced viral loads in the lungs of mice. However, the pathological damage caused by lung inflammation was more aggravated than that of the control challenge group. The level of specific IgG antibody induced by the recombinant G-CTB was significantly higher than that elicited by RMG. Compared to the RMG group, the viral load in the lungs of the G-CTB group tended to be reduced. Also, the damage caused by lung inflammation was significantly alleviated. Our study proves that HMPV G may be a valuable antigen in terms of HMPV vaccine development and offers a promising strategy for modulating the immunogenicity and safety thereof.
Insights
Developing a human metapneumovirus (HMPV) vaccine is challenging. Fusing the HMPV G protein with carrier proteins like CTB enhanced immunogenicity and reduced lung inflammation in mice, showing promise for vaccine development.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Human metapneumovirus (HMPV) causes significant lower respiratory tract infections.
- The immunogenicity of the HMPV G protein as a vaccine candidate is debated due to limited studies and weak immune responses.
Purpose of the Study:
- To evaluate the immunogenicity and efficacy of the HMPV G extracellular domain (RMG), alone and fused with cholera toxin B subunit (CTB) or CRM197, for HMPV vaccine development.
Main Methods:
- Recombinant HMPV G proteins (RMG, G-CTB, G-CRM197) were expressed and verified.
- BALB/c mice were immunized with the proteins and challenged with HMPV.
- Viral loads, antibody levels, and lung pathology were assessed.
Main Results:
- RMG alone induced weak neutralizing antibodies and aggravated lung inflammation despite modest viral load reduction.
- Fusion with CTB (G-CTB) significantly increased specific IgG antibody levels.
- The G-CTB group showed reduced viral loads and alleviated lung inflammation compared to the RMG group.
Conclusions:
- The HMPV G protein is a potential antigen for HMPV vaccine development.
- Fusion with carrier proteins like CTB can enhance immunogenicity and improve vaccine safety profiles.
