Prefusion F-based polyanhydride nanovaccine induces robust humoral and cell-mediated immunity resulting in long-lasting protection against respiratory syncytial virus

Abstract

Abstract Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in children, accounting for 7% of deaths in those less than one year of age and leading to more than $300 million in annual medical costs. As natural exposure to the virus generates insufficient immunity, there is a critical need for a safe and efficacious vaccine to prevent RSV-induced disease. We developed an intranasal vaccine, termed RSVNanoVax, composed of polyanhydride nanoparticles encapsulating the RSV prefusion F protein and a CpG1668 oligodeoxynucleotide adjuvant. RSVNanoVax prime-boost vaccination of BALB/c mice induced RSV F-directed IgG serum antibodies specific for both site 0 and site II on the F protein. Systemic antibodies maintained a robust neutralizing capacity out to at least six months post-vaccination. Vaccination with RSVNanoVax also induced F-directed IgA titers within the lungs and nasal passages as well as lung tissue-resident memory CD4 and CD8 T cells, indicating that the vaccine established both a humoral and cell-mediated immune response within the mucosal tissues. Vaccination with RSVNanoVax resulted in protection from RSV-induced disease out to at least six months post-challenge, as measured by weight loss and pulmonary dysfunction. RSVNanoVax vaccination of outbred Swiss Webster mice also elicited protection from RSV-induced disease, and resulted in complete viral clearance as early as day two after RSV challenge. High RSV F-directed antibody titers were also observed in the serum of outbred mice. Based on the robust immune response and the high level of protection observed in both inbred and outbred populations, our prefusion RSV F nanoparticle formulation represents a promising RSV vaccine candidate.