1939: Safety and Humoral Response Following the Second and Third Doses of the BNT162b2 mRNA COVID-19 Vaccine in Adolescents with Juvenile-onset Autoimmune Inflammatory Rheumatic Diseases
Merav Heshin-Bekenstein1, amit ziv2, NATASA TOPLAK3, Adi Miller Barmak4, Siman Lazauskas5, Danielle Kadishevich6, Efrat Ben Nun6, Esther Saiag7, Yonatan Butbul Aviel4, Gabi Shefer7, Sara Pel8, Ori Elkayam7 and Yosef Uziel9, 1Dana Dwek Children's Hospital, Tel Aviv Medical Center Israel, Binyamina, Israel, 2Meir Hospital, Kfar Saba, Israel, 3University of Ljubljana, Ljubljana, Slovenia, 4Rambam Medical Center, Haifa, Israel, 5Tel Aviv Medical Center, Tel Aviv, Israel, 6Meir Medical Center, Kfar Saba, Israel, 7Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, 8Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel, 9Meir Medical Center, Kfar Saba; Sackler School of Medicine, Tel Aviv University, Kfar Saba, Israel
Background/Purpose: Long-term data on the safety and dynamics of the immune response to the BNT162b2 mRNA COVID-19 vaccine in adolescents with juvenile-onset autoimmune inflammatory rheumatic diseases (AIIRD) are limited.
Methods: This international, prospective, longitudinal, multicenter study included adolescents with AIIRD (N=121) and healthy controls (N=49), with mean ages of 15.4 and 13.4 years, respectively. Among the AIIRD patients, 60% were on chronic immunomodulatory therapy. Participants received either 2-doses of mRNA vaccine: AIIRD n=93 (77.5%); controls n=19 (39%), or 3-doses AIIRD n=27 (22.5%); controls n=30 (61%) and were monitored for vaccine side-effects, disease activity and medication change from baseline to time-points post-vaccinations. In addition, antibody titers were measured serially for part of the adolescents from both cohorts, with serum anti-spike protein S1/S2 IgG titers measured at three-time points: 2-9 weeks following the second vaccine (AIIRD n=35, controls n=24), six-month time point, prior to the third vaccine (AIIRD n=34, controls n=13), and 2-9 weeks following the third vaccine dose (AIIRD n=8, controls n=9). Seropositivity was defined as an anti-S1/S2 IgG titer ≥ 15 BAU/ml.
Results: The safety profile was favorable, with most patients reporting mild or no side effects. The rheumatic disease stayed stable at 97% and 100% after the second and third vaccines, respectively. The two-dose-vaccine induced similar, high immunogenicity rates among adolescent patients and controls, with seropositivity rates of 93% and 100%, respectively (p=0.55). S1/S2 IgG titers were significantly lower in the AIIRD patients compared with controls (246±137 vs. 377±78 BAU/ml, p< 0.0001). As expected, at the 6-month measurement, before the third vaccine dose, the AIIRD cohort seropositivity rates were lower compared with the healthy controls, 86.7% vs. 100%, respectively (p=0.3), with similar S1/S2 titers (221±159 vs. 220±93 BAU/ml, p=0.98). Notably, the decline of S1/S2 IgG titers within six months was more rapid in the healthy controls as compared to the patients (-197±87 vs. -68±158 BAU/ml, p=0.03). Following the third dose, the seropositivity rate increased to 100% in both AIIRD and healthy groups, with similar S1/S2 IgG titers, 398±6 vs. 400±0 BAU/ml, respectively (p=0.35).
Conclusion: The safety profile of the BNT162b2 mRNA COVID-19 vaccine in both cohorts was excellent following all 3 doses, with an adequate immunogenic response. Adolescents with AIIRD had lower seropositivity rates following the second dose and before the third dose, as compared to healthy adolescents (93% vs. 100%, p=0.55 and 86.7% vs. 100% p=0.3, respectively). Despite the unexpectedly steeper waning immunity curve in the healthy cohort, their immunogenicity rate remained 100% six months after the 2-dose vaccine. The third vaccine dose restored the immune response in both groups of adolescents.
Disclosures: M. Heshin-Bekenstein, None; a. ziv, None; N. TOPLAK, None; A. Miller Barmak, None; S. Lazauskas, None; D. Kadishevich, None; E. Ben Nun, None; E. Saiag, None; Y. Butbul Aviel, None; G. Shefer, None; S. Pel, None; O. Elkayam, Pfizer, Eli Lilly, AbbVie/Abbott, Novartis, Janssen, Boehringer-Ingelheim; Y. Uziel, None.
