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Teams from the immunology department and internal medicine department 2 of the Pitié-Salpêtrière AP-HP hospital, Sorbonne University and Inserm, measured the antibody and cellular responses generated by a messenger RNA vaccine in patients with systemic lupus (LS). This work, coordinated by Professors Guy Gorochov (CIMI-Paris) and Zahir Amoura (National Lupus Reference Center) shows that vaccination is both well tolerated and effective, even against worrying variants. For the first time, the factors associated with a poor vaccine response in some of these patients have been identified in order to better anticipate who should benefit from reinforced protective measures and / or adapted vaccine protocols. This work was the subjectfrom an October 4 publication in the journal Annals of Rheumatic Diseases.
Systemic lupus (LS) is a chronic autoimmune disease preferentially affecting young women. The attacks are mainly articular, cutaneous, renal, cardio-respiratory, neurological and hematological. The disease is characterized by the production of autoantibodies directed against nuclear antigens. It typically evolves in spurts. For these patients, two hypotheses were considered concerning the effects of the messenger RNA vaccination: the occurrence of more frequent adverse effects, or even the exacerbation of the disease in patients with LS, or an ineffective response to vaccination for patients with LS. patients on immunosuppressants.
The teams compared the effects of vaccination in 136 patients with systemic lupus (LS). 126 of them, who received 2 doses of the BNT162b2 vaccine (Pfizer / BioNTech) and followed the entire clinical-biological surveillance course, were included in the final analysis. The two vaccine doses were separated by 21 to 28 days with a clinical-biological evaluation from the day of the first injection and up to 42 days after it (D42). The clinical activity of the disease was measured at each visit (D0, D7-14, D21-28, D42) using standardized indices. Some patients were vaccinated while their lupus disease was active.
During the 40-day follow-up, no significant change in disease activity was observed, either in patients active at the time of vaccination, or in those who showed no signs of the disease. The only notable side effects related to the vaccination were mild or moderate pain at the injection site.
A pseudo virus expressing the envelope (Spike) of the reference SARS-CoV-2 (D614G) or that of the variants B.1.1.7 (Alpha), B.1.617.1 (Kappa), B.1.617.2 (Delta ), B.1.617.3, B.1.1.28 (Gamma) and B.1.351 (Beta) was used to measure the neutralizing activity of the serum collected on D42. 82% of the patients tested were able to effectively neutralize the reference strain and the Alpha variant. As expected, a slight decrease in the neutralization efficiency of the other variants was noted, mainly for the Beta variant, neutralized by the serum of 60% of the patients tested, while the Delta variant was neutralized in 76% of cases.
At present, the vaccine response criteria are still poorly understood. Among the various treatments received against lupus, this work was able to combine methotrexate and mycophenolate mofetil, two immunosuppressive treatments, with lower rates of IgG responses to the human receptor binding domain (RBD) of SARS-CoV-2. (independently of immunosuppressive treatments). Long-term corticosteroid intake (median prednisone dose: 19 mg / day) was not, however, associated with a poor vaccine response.
This work evaluated certain therapeutic and biological criteria of vaccine response.
The study also looked at the immune status of patients at the start of the vaccination protocol. The level of circulating naive B lymphocytes (CD19 + CD27-IgD +) and the overall concentration of IgG antibodies on D0 were associated with a more intense vaccine response.
In conclusion, the vaccination of lupus patients with BNT162b2 is very well tolerated and its efficacy is reduced only in patients treated with methotrexate or mycophenolate mofetil. A pre-existing alteration in the adaptive humoral response is also associated with the poor vaccine response.
A long-acting antibody (LAAB) combination developed by AstraZeneca is to be evaluated in DisCoVeRy, the Inserm-coordinated European trial aimed at finding a treatment for COVID-19. ...
Des chercheurs et chercheuses ont mené des travaux sur la capacité de la mémoire immunitaire générée après vaccination ARNm à reconnaître et neutraliser les variants du SARS-CoV-2. ...
Quentin Moyon, Delphine Sterlin, Makoto Miyara, François Anna, Alexis Mathian, Raphael Lhote, Pascale Ghillani- Dalbin, Paul Breillat, Sasi Mudumba, Sophia de Alba, Fleur Cohen- aubart, Julien Haroche, Micheline Pha, Thi Huong Du Boutin, Hedi Chaieb, Pedro Macedo Flores, Pierre Charneau, Guy Gorochov, Zahir Amoura.
Annals of Rheumatic Diseases