Vaccine-induced antibody Fc-effector functions in humans immunized with a combination Ad26.RSV.preF/RSV preF protein vaccine.
Yannic C BartschDeniz CizmeciDansu YuanNickita MehtaJeroen TolboomEls De PaepeRoy van HeesbeenJerald SadoffChristy A ComeauxEsther HeijnenBenoit CallendretGalit AlterArangassery Rosemary BastianPublished in: Journal of virology (2023)
An Ad26.RSV.preF/RSV preF protein combination vaccine demonstrated 80.0% vaccine efficacy for the prevention of respiratory syncytial virus (RSV)-mediated lower respiratory tract disease in a phase 2b study. In addition to neutralizing antibodies, Fc-effector functions are associated with protective immunity against RSV. Here, vaccine-induced Fc-effector functions were evaluated for the Ad26.RSV.preF/RSV preF protein vaccine in a subset of participants enrolled in a phase 1/2a study. RSV preF-specific antibody subclasses, isotypes, Fcγ receptor binding, and Fc-effector functions were evaluated on days 1 (pre-vaccination), 15, 29, and 183. Compared with Ad26.RSV.preF or RSV preF protein alone, the combination vaccine induced greater Fc-effector functions, including antibody-dependent neutrophil phagocytosis and antibody-dependent natural killer cell activation. Despite RSV pre-exposure, antibody-dependent neutrophil phagocytosis and antibody-dependent natural killer cell activation were not observed at baseline but were induced de novo following vaccination. Compared with the individual vaccine components, the combination vaccine induced a more polyfunctional antibody response.IMPORTANCERespiratory syncytial virus (RSV) can cause serious illness in older adults (i.e., those aged ≥60 years). Because options for RSV prophylaxis and treatment are limited, the prevention of RSV-mediated illness in older adults remains an important unmet medical need. Data from prior studies suggest that Fc-effector functions are important for protection against RSV infection. In this work, we show that the investigational Ad26.RSV.preF/RSV preF protein vaccine induced Fc-effector functional immune responses in adults aged ≥60 years who were enrolled in a phase 1/2a regimen selection study of Ad26.RSV.preF/RSV preF protein. These results demonstrate the breadth of the immune responses induced by the Ad26.RSV.preF/RSV preF protein vaccine.
Keyphrases
- respiratory syncytial virus
- respiratory tract
- immune response
- dendritic cells
- high glucose
- diabetic rats
- regulatory t cells
- physical activity
- oxidative stress
- randomized controlled trial
- binding protein
- single cell
- clinical trial
- type iii
- bone marrow
- electronic health record
- inflammatory response
- artificial intelligence
- transcription factor
- study protocol