Adenovectors encoding RSV-F protein induce durable and mucosal immunity in macaques after two intramuscular administrations

• Published in: npj vaccines 2019-12, Vol.4 (1), p.54
• Main Authors: Salisch, N C, Izquierdo Gil, A, Czapska-Casey, D N, Vorthoren, L, Serroyen, J, Tolboom, J, Saeland, E, Schuitemaker, H, Zahn, R C
• Format: Article
• Language: English
• ISSN: 2059-0105

Respiratory Syncytial Virus (RSV) can cause severe respiratory disease, yet a licensed vaccine is not available. We determined the immunogenicity of two homologous and one heterologous intramuscular prime-boost vaccination regimens using replication-incompetent adenoviral vectors of human serotype 26 and 35 (Ad26 and Ad35), expressing a prototype antigen based on the wild-type fusion (F) protein of RSV strain A2 in adult, RSV-naive cynomolgus macaques. All regimens induced substantial, boostable antibody responses that recognized the F protein in pre- and postfusion conformation, neutralized multiple strains of RSV, and persisted for at least 80 weeks. Vaccination induced durable systemic RSV-F-specific T-cell responses characterized mainly by CD4+ T cells expressing Th1-type cytokines, as well as RSV-F-specific CD4+ and CD8+ T cells, IgG, and IgA in the respiratory tract. Intramuscular immunization with Ad26 and 35 vectors thus is a promising approach for the development of an optimized RSV vaccine expected to induce long-lasting humoral and cellular immune responses that distribute systemically and to mucosal sites.