ARTICLE: Antibody Response to Respiratory Syncytial Virus Vaccination in Immunocompromised Persons
AUTHORS: Andrew H. Karaba, Camille Hage, Isabella Sengsouk, Prasanthy Balasubramanian, Dorry L. Segev, Aaron A. A. R. Tobian, William A. Werbel
JOURNAL: JAMA. Published online December 30, 2024. doi:10.1001/jama.2024.25395
Respiratory syncytial virus (RSV) infection causes high morbidity in immunocompromised persons.1 Novel prefusion F (preF)–containing RSV vaccines showed 13- to 14-fold increases in antibody titers 1 month after vaccination and 82.6% efficacy against confirmed RSV-related lower respiratory tract disease in immunocompetent populations.2 There are no published data regarding antibody titers after RSV vaccines in immunocompromised populations or their correlation with vaccine effectiveness.3 This study measured antibody response to RSV vaccinations in immunocompromised individuals.
Methods: Within a prospective, national cohort studying viral vaccination and infections, persons with self-reported immunocompromising conditions were enrolled beginning on October 10, 2023, and followed up through July 1, 2024. The Johns Hopkins University approved this study and participants provided written informed consent. Participants reporting plans to receive adjuvanted RSVPreF3-AS01E (RSVA-AS01E, GSK) or nonadjuvanted RSVpreF (RSV-A/B, Pfizer) vaccination were asked to provide prevaccine (baseline) and 2-, 4-, and 12-week postvaccination blood samples.
Participants with paired baseline and 4-week postvaccination samples who had not received immunoglobulin products were tested for preF IgG at each postvaccination time point and neutralizing antibody (50% neutralizing titer [NT50]) at 4 weeks (eMethods in Supplement 1). The primary outcome was fold rise in antibody titers from baseline to 4 weeks, concordant with the primary immunogenicity time point in RSV vaccine trials.2,4 Seroconversion was defined as a 4-fold or greater rise in preF IgG at 4 weeks; this threshold is an accepted marker for immune response to vaccination.5 As a serological correlate of protection has not been defined, we defined high-titer neutralization as NT50 greater than or equal to standardized, prevaccine-era high-titer reference antiserum (BEI Resources, NR-4021; mean NT50, 2175). In immunocompetent persons, 4-week NT50 post–RSV vaccination ranged from 14 905 to 27 600,4 which may be associated with protection.6
Participant characteristics were compared between those who did vs did not achieve seroconversion and high-titer neutralization, using Wilcoxon rank-sum testing for continuous variables and Fisher exact testing for categorial variables, with 2-sided α less than .05 defining statistical significance. All analyses were conducted using Stata/SE version 18.0 (StataCorp).
Results: During the study period, 139 participants reported RSV vaccination, of whom 38 (27%; RSVA-AS01E, 21; RSV-A/B, 14; unspecified vaccine, 3) submitted paired baseline and 4-week postvaccination samples; most excluded participants (88/101 [87%]) lacked a baseline sample. The median (IQR) age of the 38 participants was 66 (64-72) years, 50% were female, 82% were solid organ transplant recipients, and 74% were taking 2 or more immunosuppressive medications (Table). Included and excluded participants were similar (median age, 66 vs 67 years; sex, 50% vs 65% female; solid organ transplant history, 82% vs 79%; median years since transplant, 8 vs 8.1; taking mycophenolate, 47% vs 44%; taking ≥3 immunosuppressants, 32% vs 26%). RSVA-AS01E and RSV-A/B recipients were also similar (median age, 66 vs 66 years; sex, 48% vs 57% female; solid organ transplant history, 86% vs 79%; median years since transplant, 7.7 vs 8.1; taking mycophenolate, 48% vs 57%; taking ≥3 immunosuppressants, 33% vs 29%; vaccine coadministration, 33% vs 43%).
Postvaccination, median (IQR) preF IgG rose from 87 292 (64 088-185 854) AU/mL at baseline to 626 280 (210 122-2 112 405) AU/mL at 2 weeks, 439 086 (165 026-1 837 255) AU/mL at 4 weeks, and 464 170 (255 497-2 840 694) AU/mL at 12 weeks (Figure, A). Median (IQR) 4-week preF IgG fold rise was 4.21 (1.92-13.26), including 23 participants (61%) who achieved seroconversion (Figure, B). Participant characteristics were similar among those who did (vs did not) achieve seroconversion (Table).
Median (IQR) NT50 rose from 395 (235-705) at baseline to 2978 (723-8525) at 4 weeks postvaccine (Figure, C); preF and NT50 values were positively correlated (r = .81; P < .001). Median (IQR) 4-week NT50 fold rise was 6.97 (1.75-17.70), with 22 participants (58%) achieving high-titer neutralization. Among those who did (vs did not) achieve high-titer neutralization, more persons reported use of mammalian target of rapamycin inhibitors (27% vs 0%; P = .03). Among 19 participants with high-titer neutralization and known vaccine type, 15 (79%) received RSVA-AS01E compared with 4 (21%) who received RSV-A/B (P = .02).
Discussion: This study demonstrated heterogeneous antibody response to RSV vaccines among immunocompromised persons. In contrast to universal seroconversion and preF IgG fold rises greater than 10 in immunocompetent persons,2 approximately 40% of immunocompromised participants did not seroconvert or achieve a conservative neutralization threshold postvaccination. Better neutralization was seen among RSVA-AS01E recipients, suggesting possible augmentation by the vaccine adjuvant. Low antibody titers may indicate a role for additional vaccine doses to enhance immune response among immunocompromised persons. Study limitations include the small convenience sample, absence of cellular data, and lack of correlations with vaccine effectiveness.
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