A Recombinant MVA-Based RSV Vaccine Induces T-Cell and Antibody Responses That Cooperate in the Protection Against RSV Infection

Respiratory syncytial virus (RSV) causes a respiratory disease with a potentially fatal outcome especially in infants and elderly individuals. Several vaccines failed in pivotal clinical trials, and to date, no vaccine against RSV has been licensed. We have developed an RSV vaccine based on the recombinant Modified Vaccinia Virus Ankara-BN (R) (MVA-RSV), containing five RSV-specific antigens that induced antibody and T-cell responses, which is currently tested in clinical trials. Here, the immunological mechanisms of protection were evaluated to determine viral loads in lungs upon vaccination of mice with MVA-RSV followed by intranasal RSV challenge. 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 (T11 mu MT), the IgA isotype (IgA knockout), or CD8 T cells (beta 2M knockout) revealed that complete protection from RSV challenge is dependent on CD4 and CD8 T cells as well as antibodies, including IgA. Thus, MVA-RSV vaccination optimally protects against RSV infection by employing multiple arms of the adaptive immune system.

Automated summary

Respiratory syncytial virus (RSV) is a respiratory disease that poses a potential fatality risk to infants and elderly individuals. Despite previous failed attempts, researchers have developed an RSV vaccine using recombinant Modified Vaccinia Virus Ankara-BN (MVA-RSV), which has shown promising results in clinical trials. This study demonstrates that the MVA-RSV vaccine provides optimal protection against RSV infection by activating multiple components of the adaptive immune system, including CD4 and CD8 T cells and antibodies such as IgA.