shows the titers of SARS-CoV-2 IgG antibodies directed against the viral spike protein on the day of the first (T0) (median time [95% CI]: 2 [1-2] days) and the third (T5) (median time [95% CI]: 316 [315-317] days) injection; 2 weeks after the first (T1) (median time [95% CI]: 18 [18-19] days), the second (T2) (median time [95% CI]: 45 [44-45] days) and the third (T6) (median time [95% CI]: 332 [331-335] days) injection; 3 months (T3) (median time [95% CI]: 89 [88-90] days) and 6 months (T4) (median time [95% CI]: 176 [175-177] days) after the first injection. to Serlopitant neutralizing or binding antibody classes in a cohort of 8758 healthcare workers (HCWs) studied before the emergence of B.1.1.529.3 In our study, we followed a cohort of HCWs from the two first administrations of the mRNA-1273 vaccine in January 2021 until January 28th, 2022 corresponding to two months after the injection of a 3rd dose of mRNA (either mRNA-1273 or BNT162b2 (Pfizer-BioNTech)) to verify vaccine efficacy by analyzing cases of infection, to measure the immunogenicity induced by this 3rd dose and to evaluate the protection threshold Jun proposed by Dimeglio et?al. The characteristics of the population of HCWs studied have previously been described.4 In this letter, we compared all cases of infection observed in HCWs who received a third dose (D3) of mRNA vaccine with those who did not, describing the symptoms reported by the participants, the delay between the onset of infection and the last dose of vaccine administered (D2 or D3) and finally the variant concerned. Having a positive RT-qPCR result was the criterion chosen to consider a SARS-CoV-2 infection. In this event, an analysis of the variants was carried out using an RT-qPCR method targeting the characteristic mutations of the variants (Novaplex?, Seegene Technologies, Seoul, South Korea). In parallel, participant serological follow-ups were carried out based on their initial antibody status at the time of vaccination (T0), on the vaccination schedule administered (only D2 Serlopitant versus D3) and whether they were infected or not. The quantitative analysis of the anti-trimeric spike protein specific IgG antibodies to SARS-CoV-2 was carried out using the LIAISON? SARS-CoV-2 TrimericS IgG kit (DiaSorin?, Saluggia, Italy) and calibrated with the first WHO International Standard Anti-SARS-CoV-2 Immunoglobulin.5 The kinetics of SARS-CoV-2 IgG antibodies included 7 sampling timepoints: the day of the first and third injection (T0, T5); 2 weeks after the first, second and third injections (T1, T2, T6); 3 and 6 months (T3, T4) after the first injection. In the event of infection, an additional serological test was offered to participants 2 weeks after infection (TAI). 250 participants (200 seronegative and 50 seropositive at inclusion) were followed for 1 year. Among the seronegative, 69% (20/29) were infected after the administration of 2 doses (D2) of vaccine and 9% (16/171) after a 3rd dose (D3). Among the seropositive, only 1 1 participant was infected after D2 (1/5), and Serlopitant 4 (4/45) after D3. Interestingly, the time to onset of infections in participants who received only 2 doses of vaccine (D2-infected) (n=21) occurred with a median time of [ 95% CI]: 259 [230 -268] days after administration of this 2nd dose, whereas in participants who received a third dose (D3-infected), it occurred earlier with a median time of [ 95% CI]: 36 [27-46] days after the boost (Figure?1 B,?B,1D)1D) (P 0.0001; Mann-Whitney). These last observations should be interpreted cautiously and according to the variant epidemiology. Except for 2 participants infected at the beginning of January, the infections described in the D2-infected (08/11/21-01/10/22) mostly occurred when the B.1.617.2 variant was predominant in Belgium while all the ones described in the D3-infected occurred when the B.1.1.529 variant gained dominance (12/7/21-01/28/22). Variant analysis only possible for samples with Ct 33 (n=15) confirmed the presence of the HV69/70 deletion (10/10), the N501Y (10/10) and the K417N (6/10) mutations pointing to the B.1.1.529 variant in D3-infected (10/10). The E484K mutation, pointing to the B.1.617.2 variant was found in D2-infected (5/5). Open in a separate window Figure 1 Antibody responses according to the number of vaccine doses received and the eventual occurrence of infection. figure?1. shows the titers of SARS-CoV-2 IgG antibodies directed against the viral spike protein on the day of the first (T0) (median time [95% CI]: 2 [1-2] days).