Soluble F proteins exacerbate pulmonary histopathology after vaccination upon respiratory syncytial virus challenge but not when presented on virus-like particles

Abstract

Respiratory syncytial virus (RSV) fusion (F) protein is suggested to be a protective vaccine target although its efficacy and safety concerns remain not well understood. We investigated immunogenicity, efficacy, and safety of F proteins in a soluble form or on virus-like particle (F-VLP). F VLP preferentially elicited IgG2a antibody and T helper type 1 (Th1) immune responses whereas F protein induced IgG1 isotype and Th2 responses. Despite lung viral clearance after prime or prime-boost and then RSV challenge, F protein immune mice displayed weight loss and lung histopathology and high mucus production and eosinophils. In contrast, prime or prime-boost vaccination of F VLP induced effective protection, prevented infiltration of eosinophils and vaccine- enhanced disease after challenge. This study provides insight into developing an effective and safe RSV vaccine candidate.

Natural Killer and CD8 T Cells Contribute to Protection by Formalin Inactivated Respiratory Syncytial Virus Vaccination under a CD4-Deficient Condition

“…4C ). Previous studies have reported no detection or low levels of eosinophil infiltration in RSV infected naïve animals and in less severe human patients ( 11 12 20 23 ). In consistent, we observed no eosinophils or below the detection limit in the lung from WT and CD4KO mice without FI-RSV vaccination after challenge with RSV ( Fig.…”

“…The fixed lung samples were processed and then embedded paraffin blocks for tissue sections. Lung tissue sections with a thickness of 5 μm were stained with H&E or hematoxylin and Congo red (H&CR) to evaluate lung histopathologic changes and eosinophil infiltration, respectively as previously described ( 13 20 ).…”

Recombinant Live Attenuated Influenza Virus Expressing Conserved G-Protein Domain in a Chimeric Hemagglutinin Molecule Induces G-Specific Antibodies and Confers Protection against Respiratory Syncytial Virus

“…After processing, the tissues were embedded in paraffin and sectioned of 5 µm to stain with hematoxylin and eosin (H&E). Lung histopathology after H&E staining was blind scored in the area of airways, blood vessels, and interstitial spaces with scales of 0 to 3 (0: none, 1: mild, 2: moderate, 3: severe), as detailed in previous studies [ 26 , 27 , 28 ].…”

Progress in the development of virus-like particle vaccines against respiratory viruses

“…Interestingly, prime immunization of mice with RSV F VLP vaccine induced Th1biased immune response, preventing the induction of lung histopathology due to subsequent FI-RSV vaccination [114]. Unique immunogenic properties of RSV F VLP platforms were evident by a study reporting that soluble F protein vaccination exacerbated pulmonary histopathology upon RSV challenge but not when presented on VLPs in a mouse model [115]. Most individuals are considered to be infected with RSV by ages two to three years old but live RSV infection did not provide long-term protective immunity.…”