TY - JOUR
T1 - Immunogenicity and safety of the CoronaVac inactivated vaccine in patients with autoimmune rheumatic diseases
T2 - a phase 4 trial
AU - Medeiros-Ribeiro, Ana C.
AU - Aikawa, Nadia E.
AU - Saad, Carla G.S.
AU - Yuki, Emily F.N.
AU - Pedrosa, Tatiana
AU - Fusco, Solange R.G.
AU - Rojo, Priscila T.
AU - Pereira, Rosa M.R.
AU - Shinjo, Samuel K.
AU - Andrade, Danieli C.O.
AU - Sampaio-Barros, Percival D.
AU - Ribeiro, Carolina T.
AU - Deveza, Giordano B.H.
AU - Martins, Victor A.O.
AU - Silva, Clovis A.
AU - Lopes, Marta H.
AU - Duarte, Alberto J.S.
AU - Antonangelo, Leila
AU - Sabino, Ester C.
AU - Kallas, Esper G.
AU - Pasoto, Sandra G.
AU - Bonfa, Eloisa
N1 - Funding Information:
We thank the contribution of the Central Laboratory Division, Registry Division, Security Division, IT Division, Superintendence, Pharmacy Division and Vaccination Center for their technical support. We also thank the volunteers for participating in the three in-person visits of the protocol and for handling the biological material, and those responsible for the follow-up of all participants. This study was sponsored by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (no. 2015/03756–4 to N.E.A., S.G.P., C.A.S. and E.B.; no. 2017/14352-7 to T.P., no. 2018/09937-9 to V.A.O.M., no. 2020/11677-5 to G.B.H.D.; and no. 2019/21173-7 to C.T.R.) and from Conselho Nacional de Desenvolvimento Científico e Tecnológico (no. 305242/2019-9 to E.B.; no. 304984/2020-5 to C.A.S.; no. 305556/2017-7 to R.M.R.P.; and no. 303379/2018-9 to S.K.S.). Instituto Butantan supplied the study product and had no other role in the trial.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/10
Y1 - 2021/10
N2 - CoronaVac, an inactivated SARS-CoV-2 vaccine, has been approved for emergency use in several countries. However, its immunogenicity in immunocompromised individuals has not been well established. We initiated a prospective phase 4 controlled trial (no. NCT04754698, CoronavRheum) in 910 adults with autoimmune rheumatic diseases (ARD) and 182 age- and sex-frequency-matched healthy adults (control group, CG), who received two doses of CoronaVac. The primary outcomes were reduction of ≥15% in both anti-SARS-CoV-2 IgG seroconversion (SC) and neutralizing antibody (NAb) positivity 6 weeks (day 69 (D69)) after the second dose in the ARD group compared with that in the CG. Secondary outcomes were IgG SC and NAb positivity at D28, IgG titers and neutralizing activity at D28 and D69 and vaccine safety. Prespecified endpoints were met, with lower anti-SARS-Cov-2 IgG SC (70.4 versus 95.5%, P < 0.001) and NAb positivity (56.3 versus 79.3%, P < 0.001) at D69 in the ARD group than in the CG. Moreover, IgG titers (12.1 versus 29.7, P < 0.001) and median neutralization activity (58.7 versus 64.5%, P = 0.013) were also lower at D69 in patients with ARD. At D28, patients with ARD presented with lower IgG frequency (18.7 versus 34.6%, P < 0.001) and NAb positivity (20.6 versus 36.3%, P < 0.001) than that of the CG. There were no moderate/severe adverse events. These data support the use of CoronaVac in patients with ARD, suggesting reduced but acceptable short-term immunogenicity. The trial is still ongoing to evaluate the long-term effectiveness/immunogenicity.
AB - CoronaVac, an inactivated SARS-CoV-2 vaccine, has been approved for emergency use in several countries. However, its immunogenicity in immunocompromised individuals has not been well established. We initiated a prospective phase 4 controlled trial (no. NCT04754698, CoronavRheum) in 910 adults with autoimmune rheumatic diseases (ARD) and 182 age- and sex-frequency-matched healthy adults (control group, CG), who received two doses of CoronaVac. The primary outcomes were reduction of ≥15% in both anti-SARS-CoV-2 IgG seroconversion (SC) and neutralizing antibody (NAb) positivity 6 weeks (day 69 (D69)) after the second dose in the ARD group compared with that in the CG. Secondary outcomes were IgG SC and NAb positivity at D28, IgG titers and neutralizing activity at D28 and D69 and vaccine safety. Prespecified endpoints were met, with lower anti-SARS-Cov-2 IgG SC (70.4 versus 95.5%, P < 0.001) and NAb positivity (56.3 versus 79.3%, P < 0.001) at D69 in the ARD group than in the CG. Moreover, IgG titers (12.1 versus 29.7, P < 0.001) and median neutralization activity (58.7 versus 64.5%, P = 0.013) were also lower at D69 in patients with ARD. At D28, patients with ARD presented with lower IgG frequency (18.7 versus 34.6%, P < 0.001) and NAb positivity (20.6 versus 36.3%, P < 0.001) than that of the CG. There were no moderate/severe adverse events. These data support the use of CoronaVac in patients with ARD, suggesting reduced but acceptable short-term immunogenicity. The trial is still ongoing to evaluate the long-term effectiveness/immunogenicity.
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U2 - 10.1038/s41591-021-01469-5
DO - 10.1038/s41591-021-01469-5
M3 - Article
C2 - 34331051
AN - SCOPUS:85111630893
VL - 27
SP - 1744
EP - 1751
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
IS - 10
ER -