Mechanism of vaccine-induced immune responses
ADNKA
REGRESSION
Because we observed that the addition of RSV preF protein to Ad26.RSV.preF improved some antibody and Fc-effector function responses induced by Ad26.RSV.preF alone, we used a limited number of samples from the initial safety cohort of the regimen selection study to further evaluate the specific contributions of Ad26.RSV.preF and RSV preF protein to vaccine-induced immune responses. Baseline-corrected RSV preF-specific humoral immunity and Fc-effector functions were profiled on day 15 for participants receiving the Ad26.RSV.preF/RSV preF protein combination vaccine, Ad26.RSV.preF alone, RSV preF protein alone, or placebo.Consistent with the results above, the Ad26.RSV.preF/RSV preF protein vaccine induced substantial increases in RSV preF-specific IgG1, IgG2, IgA1, IgA2, and IgM compared with placebo (RSV preF-specific IgG, IgA, and IgM trajectories. RSV preF-specific (a) IgG1, (b) IgG2, (c) IgG3, (d) IgG4, (e) IgA1, (f) IgA2, and (g) IgM were measured in serum samples collected at day 15 for participants receiving the Ad26.RSV.preF/RSV preF protein combination vaccine (Antibodies elicited by the Ad26.RSV.preF/RSV preF protein combination vaccine also showed substantial binding to Fc receptors, including FcαR, FcγR2a, FcγR2B, FcγR3a, and FcγR3b, compared with placebo, consistent with the results above (RSV preF-specific Fc receptor binding induced by Ad26.RSV.preF, RSV preF protein, and the Ad26.RSV.preF/RSV preF protein combination vaccine. RSV preF-specific (a) FcαR, (b) FcγR2a, (c) FcγR2b, (d) FcγR3a, and (e) FcγR3b binding were measured in serum samples collected at day 15 for participants receiving the Ad26.RSV.preF/RSV preF protein combination vaccine (The Ad26.RSV.preF/RSV preF protein combination vaccine showed substantial induction of RSV preF-specific Fc-effector functions, including ADCD, ADNP, and ADNKA, compared with placebo, consistent with the results above (RSV preF-specific Fc-effector functions induced by Ad26.RSV.preF, RSV preF protein, and the Ad26.RSV.preF/RSV preF protein combination vaccine. RSV preF-specific (a) ADCD, (b) ADNP, (c) ADCP, and (d) ADNKA were measured in serum samples collected at day 15 for participants receiving the Ad26.RSV.preF/RSV preF protein combination vaccine (Partial least squares regression (PLS-R) analysis of immune responses induced by the Ad26.RSV.preF/RSV preF protein combination vaccine, RSV preF protein alone, and Ad26.RSV.preF alone showed that each regimen induced distinct immune responses (PLS-R analysis of humoral and Fc-effector responses. PLS-R analysis was used to profile humoral and Fc-effector responses for participants receiving Ad26.RSV.preF alone (