A Single Shot Pre-fusion-Stabilized Bovine RSV F Vaccine is Safe and Effective in Newborn Calves with Maternally Derived Antibodies

Abstract

Achieving safe and protective vaccination against respiratory syncytial virus (RSV) in infants and in calves has proven a challenging task. The design of recombinant antigens with a conformation close to their native form in virus particles is a major breakthrough. We compared two subunit vaccines, the bovine RSV (BRSV) pre-fusion F (preF) alone or with nanorings formed by the RSV nucleoprotein (preF+N). PreF and N proteins are potent antigenic targets for neutralizing antibodies and T cell responses, respectively. To tackle the challenges of neonatal immunization, three groups of six one-month-old calves with maternally derived serum antibodies (MDA) to BRSV received a single intramuscular injection of PreF, preF+N with MontanideTM ISA61 VG (ISA61) as adjuvant or only ISA61 (control). One month later, all calves were challenged with BRSV and monitored for virus replication in the upper respiratory tract and for clinical signs of disease over one week, and then post-mortem examinations of their lungs were performed. Both preF and preF+N vaccines afforded safe, clinical, and virological protection against BRSV, with little difference between the two subunit vaccines. Analysis of immune parameters pointed to neutralizing antibodies and antibodies to preF as being significant correlates of protection. Thus, a single shot vaccination with preF appears sufficient to reduce the burden of BRSV disease in calves with MDA.

Single-Shot Vaccines against Bovine Respiratory Syncytial Virus (BRSV): Comparative Evaluation of Long-Term Protection after Immunization in the Presence of BRSV-Specific Maternal Antibodies

“…Indeed, in both humans and cattle, this would make vaccination more robust and would enable vaccine usage at a large scale in different societal, economical and geographical contexts. Based on others and our previous results [ 11 , 12 , 13 , 14 , 30 ], bovine PreF and ΔSHrBRSV both appear promising candidates, either as new vaccines against BRSV in cattle, or as proof of concept for vaccines against HRSV in babies. In the present study, a BRSV calf model was used to compare the efficacy and the safety of a single administration of each of these vaccines and a commercial BRSV vaccine, three months post-vaccination.…”

“…BRSV-specific cell-mediated immune responses were analyzed by IFNγ-ELISpot of γ/δ-depleted PBMCs, stimulated either with heat-inactivated BRSV-infected cell lysate at 10 4.5 TCID 50 /mL (isolate no. 9402022 Denmark, kindly provided by Pr L E Larsen, University of Copenhagen, Department of Veterinary and Animal Sciences, Frederiksberg C, Denmark) or uninfected cell lysate, as previously described [ 12 ].…”

“…In a subsequent experiment with a more stringent situation of calves with BRSV-specific MDA, a single i.m. injection with 100-µg PreF in ISA61 VG adjuvant (Seppic, Paris, France), alone or combined with HRSV N protein–nano rings (N Nano rings), induced near complete clinical and virological protection against the challenge with virulent BRSV four weeks later [ 12 ]. Protection was again found to be associated with a strong induction of neutralizing antibodies.…”

Applications of Nanovaccines for Disease Prevention in Cattle

“…Polymeric particles delivered intranasally to calves induced significant amounts of nasal IgA (Kavanagh et al, 2003(Kavanagh et al, , 2013Mansoor et al, 2014;Pan et al, 2014;McGill et al, 2018McGill et al, , 2019. Similarly, intramuscular delivery of particles induced both mucosal and systemic antibody responses (Riffault et al, 2010(Riffault et al, , 2020. Subcutaneous delivery of a polyanhydride vaccine implant to bovine species induced CD4+ T cell production and a humoral response (Boggiatto et al, 2019).…”

“…In mice, Nnanorings carrying the FsII neutralizing epitope from antigenic site II of the F protein, the same epitope recognized by the monoclonal antibody Palivizumab (SYNAGIS R , AstraZeneca), induced partial protection against HRSV infection (Hervé et al, 2017). More recently, the N-nanorings were co-administered with the prefusion F protein from BRSV and shown to induce complete protection from the experimental challenge (Riffault et al, 2020).…”