Respiratory Syncytial Virus Vaccination Strongly Induces RSVpreF-specific IgG and Neutralizing Activity in...

Protein-based respiratory syncytial virus (RSV) prefusion F (RSVpreF) vaccines show promising immunogenicity in immunocompromised individuals. We have recently shown that RSV-specific CD4 T-cell responses and IgG antibodies were significantly induced, but data on functional humoral responses as well as associations between cellular and humoral immunological endpoints remain limited. We therefore extended our previous studies and performed a head-to-head assessment of vaccine-specific RSVpreF IgG and neutralizing antibody activity across different immunocompromised populations, including kidney and lung transplant recipients, patients on hemodialysis, and patients with CKD.

Conformation-specific RSVpreF-specific IgG levels and RSV-neutralizing plasma activity were assessed before and 13-18 d after RSV vaccination in 61 patients with chronic kidney disease (CKD), 15 patients receiving hemodialysis, 46 kidney transplant (KTx) recipients, and 31 lung transplant (LuTx) recipients. RSVpreF-specific IgG was measured by ELISA and neutralizing activity using an RSV-pseudovirus assay. Furthermore, comprehensive correlation analyses were carried out to assess associations between vaccine-induced humoral immune parameters and cellular immunity.

Vaccination significantly increased RSVpreF-specific IgG (P ≤ 0.0001) and neutralizing activity in all groups (P = 0.002 to P < 0.0001). Median fold increases in IgG were highest in patients with CKD (11.9-fold), followed by patients on hemodialysis (7.8-fold) and LuTx recipients (7.6-fold), and lowest in KTx-recipients (3.3-fold). Neutralizing activity showed a similar pattern, with fold increases of 10.9, 5.4, 7.5, and 2.6, respectively. MMF/MPA use and vaccination within the first year posttransplant were associated with reduced humoral responses. RSVpreF-specific IgG correlated strongly with neutralizing activity (r = 0.664, P < 0.0001), whereas correlations with CD4 T-cell responses were less pronounced.

RSV vaccination induces robust functional humoral immunity in all tested immunocompromised patient groups, but responses are lowest in kidney transplant recipients. Among transplant recipients, responses were reduced within the first year after transplantation and in patients on MMF/MPA, supporting the need for optimized vaccination strategies in these patient groups.