Epicutaneous immunization using synthetic virus-like particles efficiently boosts protective immunity to respiratory syncytial virus. Issue 32 (22nd July 2021)

• Record Type: Journal Article
• Authors: Hervé, Pierre-Louis; Dhelft, Véronique; Zuniga, Armando; Ghasparian, Arin; Rassek, Oliver; Yim, Kevin C.; Donne, Nathalie; Lambert, Paul-Henri; Benhamou, Pierre-Henri; Sampson, Hugh A.; Mondoulet, Lucie
• Is Part Of: Vaccine. Volume 39:Issue 32(2021)
• Page Start: 4555
• Page End: 4563
• Publication Date: 2021-07-22
• Subjects: FsII neutralizing conformational epitope located in the antigenic site II of the RSV fusion glycoprotein -- PLA Palivizumab-Like Antibody -- SC Subcutaneous -- SVLPs Synthetic Virus-Like Particles -- VAERD vaccine-associated enhanced respiratory disease; Nanoparticle-based vaccine -- Epicutaneous vaccine -- RSV-neutralizing antibodies -- Synthetic virus like particles -- Vaccine boost; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2021.03.081
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: An epicutaneous booster vaccine against RSV was investigated in mouse model. It combines synthetic VLP as antigen and epicutaneous patches as delivery platform. Epicutaneous vaccine efficiently boosted RSV-neutralizing antibody titers. Epicutaneous boost vaccine significantly decreased RSV load in challenged mice. Epicutaneous boost vaccine induced Th1 effectors in lungs. Abstract: Despite the substantial health and economic burden caused by RSV-associated illness, no vaccine is available. The sole licensed treatment (palivizumab), composed of a monoclonal neutralizing antibody, blocks the fusion of the virus to the host cell but does not prevent infection. The development of a safe and efficacious RSV vaccine is therefore a priority, but also a considerable challenge, and new innovative strategies are warranted. Most of the adult population encounter regular RSV infections and can elicit a robust neutralizing antibody response, but unfortunately it wanes over time and reinfections during subsequent seasons are common. One approach to protect the mother and young infant from RSV infection is to administer a vaccine capable of boosting preexisting RSV immunity during pregnancy, which would provide protection to the fetus through passive transfer of maternal antibodies, thus preventing primary RSV infection in newborns during their first months of life. Here, we describe the preclinical evaluation of an epicutaneous RSV vaccine booster that combines epicutaneous patches as a delivery platform and a Synthetic Virus-Like Particles (SVLP)-based vaccine displaying multiple RSV F-protein site II (FsII, palivizumab epitope) mimetic as antigen (V-306). We demonstrated in mice that epicutaneous immunization with V-306 efficiently boosts preexisting immunity induced by the homologous V-306 administered subcutaneously. This boosting was characterized by a significant increase in F- and FsII-specific antibodies capable of competing with palivizumab for its target antigen and neutralize RSV. More importantly, epicutaneous booster immunization with V-306 significantly decreased lung viral replication in experimental mice after intranasal RSV challenge, without inducing enhanced RSV disease. In conclusion, an epicutaneous booster vaccine based on V-306 is safe and efficacious in enhancing RSV preexisting immunity in mice. This needle-free vaccine candidate would be potentially suited as a booster vaccine for vulnerable populations such as young infants via pregnant women, and the elderly.