Bovine Respiratory Syncytial Virus Nanovaccine Induces Long-Lasting Humoral Immunity in Mice

With limited therapies and vaccines available, human respiratory syncytial virus (HRSV) has a significant negative health impact on all age groups but particularly on infants, young children, and older adults. Bovine respiratory syncytial virus (BRSV) is pathogenically and antigenically similar to HRSV. Building upon previous studies using a BRSV nanovaccine coencapsulating multiple proteins, this work demonstrates the development and comparative evaluation of a coencapsulated nanovaccine to a cocktail nanovaccine formulation composed of polyanhydride nanoparticles encapsulating BRSV postfusion (F) glycoprotein and CpG ODN 1668 coadjuvant delivered simultaneously with nanoparticles encapsulating BRSV attachment glycoprotein (G) and CpG ODN 1668. These nanovaccine formulations were administered to C57BL/6 mice by one of two prime-boost regimens (i.e., intranasal/intranasal or intranasal/subcutaneous) followed by assessment of humoral immunity. The cocktail nanovaccine induced sustained anti-F and anti-G serum IgG antibody responses for 12 weeks postprimary immunization. Using polyanhydride particles to deliver G protein in a prime-boost regime also significantly induced serum anti-G antibodies compared to protein and coadjuvant alone. Serum IgG induced by the nanovaccine demonstrated virus-neutralizing capability from 42 to 119 days postprimary immunization. Further, anti-F IgG antibodies were detected in the bronchoalveolar lavage fluid of vaccinated animals. Finally, the nanovaccine induced long-lived anti-F antibody secreting plasma cells that were detectable in the bone marrow 205 days postprimary immunization. Overall, the BRSV nanovaccine(s) successfully induced long-lived humoral immune responses capable of virus neutralization, making this a promising vaccine candidate for further evaluation in other relevant animal models.