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

Abstract

The induction of long-lasting clinical and virological protection is needed for a successful vaccination program against the bovine respiratory syncytial virus (BRSV). In this study, calves with BRSV-specific maternally derived antibodies were vaccinated once, either with (i) a BRSV pre-fusion protein (PreF) and MontanideTM ISA61 VG (ISA61, n = 6), (ii) BRSV lacking the SH gene (ΔSHrBRSV, n = 6), (iii) a commercial vaccine (CV, n = 6), or were injected with ISA61 alone (n = 6). All calves were challenged with BRSV 92 days later and were euthanized 13 days post-infection. Based on clinical, pathological, and proteomic data, all vaccines appeared safe. Compared to the controls, PreF induced the most significant clinical and virological protection post-challenge, followed by ΔSHrBRSV and CV, whereas the protection of PreF-vaccinated calves was correlated with BRSV-specific serum immunoglobulin (Ig)G antibody responses 84 days post-vaccination, and the IgG antibody titers of ΔSHrBRSV- and CV-vaccinated calves did not differ from the controls on this day. Nevertheless, strong anamnestic BRSV- and PreF-specific IgG responses occurred in calves vaccinated with either of the vaccines, following a BRSV challenge. In conclusion, PreF and ΔSHrBRSV are two efficient one-shot candidate vaccines. By inducing a protection for at least three months, they could potentially improve the control of BRSV in calves.

Longitudinal study of the immune response and memory following natural bovine respiratory syncytial virus infections in cattle of different age

“…In agreement with data in vaccinated calves and in naturally infected children [11,27], virus-specific cellular responses were not detectable in the peripheral circulation of our cattle 2 months post infection. Similarly, serum IgA responses were only detectable in some animals and were mostly of short duration.…”

“…Local (respiratory) anamnestic BRSV-specific IgA might additionally be important, especially at the peak of immunity [17,19], but the IgA memory seems to be short, at least when induced by live intranasal vaccines [27]. Unfortunately, nasal secretions for antibody analyis were not collected after reinfection in this study.…”

“…In contrast to BRSV-specific serum and nasal IgA and circulating T cell memory, serum IgG and BRSV-neutralising serum antibodies were long lasting. The humoral immune response directed against PreF, which previously was identified as key in protection against RSV [22,27], was characterised by a strong memory response. A partial virological protection was obtained after four years, as indicated by reduced quantities of BRSV-RNA in nasal secretions.…”

“…Since experimental vaccines based on only the PreF protein have demonstrated good efficacy in calves [22,27,38], the N protein could potentially serve as DIVA protein in the future. The detection of N-specific antibodies in PreF-vaccinated animals could thereby be used to identify the occurrence of BRSV infections and indicate when the duration of vaccine-induced protective immunity has waned.…”

Interactions between the Nucleoprotein and the Phosphoprotein of Pneumoviruses: Structural Insight for Rational Design of Antivirals

“…No vaccine is available against hRSV and hMPV. Although several vaccines against bRSV and aMPV are commercialized, their efficacy remains limited [27,[31][32][33][34]. In this context, the development of antiviral drugs with a wide spectrum represents an alternative to human vaccination.…”