Immunogenicity and protective efficacy of an RSV G S177Q central conserved domain nanoparticle vaccine

Frontiers in Immunology

Immunology

Rebecca M. DuBois¹  Maria G. Juarez¹  Samuel J. Nangle¹  Jackelyn Murray²  Harrison C. Bergeron²  Ralph A. Tripp² 

[1] Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, United States;Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, United States;

关键词: RSV;    G protein;    structure-guided vaccine;    nanoparticle vaccine;    neutralizing Abs;   

DOI  :  10.3389/fimmu.2023.1215323

 received in 2023-05-01, accepted in 2023-06-12,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionRespiratory syncytial virus (RSV) can cause lower respiratory tract disease in infants and elderly populations. Despite decades of research, there remains no safe and approved RSV vaccine. Previously, we showed that an RSV G glycoprotein subunit vaccine candidate with a single point mutation within the central conserved domain (CCD), i.e. S177Q, considerably improved immunogenicity.MethodsHere, we examine the development of nanoparticle (NP) vaccines having either an RSV G protein CCD with wild-type sequence (NPWT) or an S177Q mutation (NP-S177Q). The NP vaccine immunogens were adjuvanted with monophosphoryl lipid A (MPLA), a TLR4 agonist to improve Th1- type responses. BALB/c mice were primed with 10 μg of NP-WT vaccine, NPS177Q, or vehicle, rested, and then boosted with a high (25 μg) or low (10 μg) dose of the NP-WT or NP-S177Q homologous candidate and subsequently challenged with RSV A2.ResultsThe results showed that mice boosted with NP-S177Q developed superior immunogenicity and neutralizing antibodies compared to NP-WT boosting. IgG from either NP-S177Q or NP-WT vaccinated mice did not interfere with fractalkine (CX3CL1) binding to CX3CR1 and effectively blocked G protein CX3C-CX3CR1 binding. Both NP-WT and NP-S177Q vaccination induced similar neutralizing antibodies to RSV in challenged mice compared to vehicle control. NP-S177Q boosting improved correlates of protection including reduced BAL cell infiltration following RSV challenge. However, the NP vaccine platform will require improvement due to the poor solubility and the unexpectedly weaker Th1-type IgG2a response.DiscussionThe results from this study support further NP-S177Q vaccine candidate development.

【 授权许可】

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Copyright © 2023 Bergeron, Murray, Juarez, Nangle, DuBois and Tripp