DNA Immunization with Plasmids Encoding Fusion and Nucleocapsid Proteins of Bovine Respiratory Syncytial Virus Induces a Strong Cell-Mediated Immunity and Protects Calves against Challenge

Abstract

Respiratory syncytial viruses (RSV) are one of the most important respiratory pathogens of humans and cattle, and there is currently no safe and effective vaccine prophylaxis. In this study, we designed two codon-optimized plasmids encoding the bovine RSV fusion (F) and nucleocapsid (N) proteins and assessed their immunogenicity in young calves. Two administrations of both plasmids elicited low antibody levels but primed a strong cell-mediated immunity characterized by lymphoproliferative response and gamma interferon production in vitro and in vivo. Interestingly, this strong cellular response drastically reduced viral replication, clinical signs, and pulmonary lesions after a highly virulent challenge. Moreover, calves that were further vaccinated with a killed-virus vaccine developed high levels of neutralizing antibody and were fully protected following challenge. These results indicate that DNA vaccination could be a promising alternative to the classical vaccines against RSV in cattle and could therefore open perspectives for vaccinating young infants.

Overcoming T-Cell-Mediated Immunopathology to Achieve Safe Respiratory Syncytial Virus Vaccination

“…In addition, RSV challenge of calves previously immunized with FI-RSV results in enhanced pulmonary disease in the presence of a Th2 response [66,67]. The use of recombinant vaccinia virus vaccines and DNA vaccines has been effective at reducing the development of disease in this natural host model [68,69]. These results provide hope for the future development of a safe and effective vaccine for use in humans.…”

A new subunit vaccine based on nucleoprotein nanoparticles confers partial clinical and virological protection in calves against bovine respiratory syncytial virus

“…Similarly, immunization of young calves with a recombinant vaccinia virus expressing the BRSV N protein induced non-neutralizing antibodies and primed BRSV-specific proliferative T response and IFN-␥ production that resulted in reduction of viral replication in the upper and lower respiratory tract [17]. DNA immunization by two administrations of plasmids encoding BRSV-F and N proteins primed a strong cell-mediated immunity in calves, which drastically reduced viral replication, clinical signs and pulmonary lesions after a highly virulent challenge [18]. More recently a nucleocapsidbased DNA prime-protein boost vaccination was shown to confer protection against BRSV replication and lung pathology [19].…”

Efficient Lung Recruitment of Respiratory Syncytial Virus-Specific Th1 Cells Induced by Recombinant Bacillus Calmette-Guérin Promotes Virus Clearance and Protects from Infection

“…These viral proteins are the main antigenic targets of RSV-specific CTL responses, among which the nucleoprotein N is a major carrier of CTL epitopes in human and cattle (30)(31)(32). Furthermore, N protein is the most conserved viral protein between RSV human isolates (33,34), and other strategies that had used RSV-N protein for vaccine design were also effective (32,(35)(36)(37)(38). Therefore, our next aim was to study the cellular mechanism by which BCG-N induces protection against RSV infection.…”