• Vaccine Name: MVA - RSV
• Target Pathogen: Human Respiratory Syncytial Virus
• Target Disease: Respiratory tract disease
• Manufacturer: Bavarian Nordic
• Type: Recombinant vector vaccine
• Status: Licensed
• Host Species for Licensed Use: Human
• Host Species as Laboratory Animal Model: Used two mouse models to shed light on MVA RSV induced immune mechanisms of protection against RSV infection.
• Antigen: (Endt et al., 2022) RSV fusion protein (F), glycoprotein (G), nucleoprotein (N), transcription elongation factor from RSV A, and glycoprotein from RSV strain B.
• Preparation: (Endt et al., 2022)MVA-RSV was generated by homologous recombination. Primary Chicken embryo fibroblast cells were infected with MVA -BN and transferred with recombination plasmids. During homologous recombination, sequences within the plasmid homologous to the insertion sites of the MVA - BN genome recombine with their corresponding sequences within the viral genome and target the trans genes into the respective integration site of MVA - BN. MVA-RSV was further propagated in CEF cells at serum-free conditions. After insertion of the antigens into the MVA-BN genome, genetically pure clones were isolated by repeated rounds of limiting dilution and plaque purification. were isolated by repeated rounds of limiting dilution and plaque purification. A final clone was amplified, and a stock was prepared.
• Immunization Route: intranasal immunization
• Storage: (Endt et al., 2022) Production was conducted in roller bottles seeded with primary CEF cells under serum-free conditions. Infected CEF lysates were sonicated, purified, and concentrated using a standardized two-step sucrose cushion centrifugation procedure. Vaccine infectious titer, sequence identity, and integrity were confirmed.
• Description: (Endt et al., 2022)The MVA RSV contains five SV specific antigens that induced antibody and T cell responses which is currently being tested in the clinical trials for people older than 55 years of age. Depletion of CD4 or CD8 T cells, serum transfer, and the use of genetically engineered mice lacking the ability to generate either RSV-specific antibodies, the IgA isotope, or CD8 T cells revealed that complete protection from RSV infection is dependent on CD4 and CD8 T cells as well as antibodies, including IgA. MVA-RSV vaccination optimally protects against RSV infection by employing multiple arms of the adaptive immune system.

Mouse Response

• Host age: mice were between 12- 24 weeks(Endt et al., 2022)
• Vaccination Protocol: (Endt et al., 2022)IgA deficient mice at the age of 12 to 24 weeks, CD8 deficient mice the insertion sites of the MVA - BN genome recombine with their corresponding sequences within the viral genome and target the trans genes into the respective integration site of MVA - BN. Mice were administered intranasally (IN) with 100 μl of the MVA-RSV vaccine at 1 × 108 TCID50 per dose at Days 0 and 21. IN challenge was performed with 100 μl of RSV-A2 at 1 × 106 pfu at Day 35 (9, 15). Control animals received TRIS-buffered saline, pH 7.7. For IN applications, mice were anesthetized with a mixture of Fentanyl, Midazolam, and Medetomidine and anesthesia was antagonized with a mixture of Naloxone, Flumazenil, and Atipamezole. After challenge, animals were monitored daily, and body weight was measured. Animals were sacrificed 4 days post challenge.
• Efficacy: (Endt et al., 2022) MSV - RSV induced both broad T cell responses against all encoded RSV antigens and humoral responses against RSV A and RSV B. These results suggest that MVA - RSV may activate various adaptive immune responses against RSV that could contribute to different pathways of protection.
• Description: (Endt et al., 2022)After vaccination with MVA-RSV, clearance of RSV from murine lungs was only complete in the presence of RSV-specific antibodies, including mucosal IgA, as well as CD4 and CD8 T cells. MVA-RSV induces immune parameters from all arms of the adaptive immune system, which together warrant sterilizing protection against RSV exposure.