Timeline kinetics of protective immunity to SARS-CoV-2 upon primary vaccination and humoral response to variants after booster dose.

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged, imposing the need for periodic booster doses. However, whether booster doses should be applied to the entire population or groups, and the booster doses interval, remains unclear. In this study, we evaluated humoral reactivity kinetics from before the first dose to 180 days after the third booster dose in different schedules in a well-controlled health worker cohort. Among the 2,506 employees, the first 500 vaccinated health workers were invited to participate. The third booster dose was administered 8 months after the first dose. Among the invited participants, 470 were included in the study; 258 received inactivated vaccine CoronaVac (VAC group) and 212 received viral vector vaccine ChAdOx1 (AZV group). The groups were homogeneous in terms of age and sex. 347 participants were followed up after the booster dose with AZV or BNT162b2 (Pfizer, BNT group): 63 with VAC/AZV, 117 with VAC/BNT, 72 with the AZV/AZV and 95 with AZV/BNT schedules. Blood samples were collected immediately before, 28 days after each dose and 180 days after the primary vaccination and booster dose. Anti-SARS-CoV-2 antibodies were measured by chemiluminescence and plaque reduction neutralization test (PRNT). Plasma immune mediators were quantified using a multiplex immunoassay. Geometric mean of antibodies increased 28 days after the second dose with 100 % seroconversion rate in both groups and decreased 180 days after the first dose. In the baseline-seropositive VAC group, the levels of plasma immune mediators increased after the second dose. Booster dose was applied at 4-6 months after the primary vaccination. Heterologous booster in VAC or AZV primary vaccinees were effective maintaining the titers of anti-SARS-CoV-2 antibodies even after 6 months of follow-up. The heterologous schedule induced higher and stable antibody reactivity, even after 180 days, protecting to ancestral (Wuhan), Delta, and Omicron variants.

Previous biological therapy and impairment of the IFN-γ/IL-10 axis are associated with low immune response to 17DD-YF vaccination in patients with spondyloarthritis.

Yellow fever (YF) vaccination is known to induce a suboptimal response in patients with autoimmune diseases (AIDs). To date, few studies have focused on the performance of 17DD-YF vaccination in patients with spondyloarthritis (SpA). In general, patients with SpA are young and have less comorbidities than other patients with AIDs, and frequently receive biological disease-modifying antirheumatic drugs (DMARDs) that may impact their response to vaccines. Taking this background information, the present study aimed to investigate whether the use of biological DMARDs, even after planned washout, or disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), would impact the overall performance of planned 17DD-YF primary vaccination in patients with SpA. For this purpose, 74 subjects were enrolled in a prospective study, including adult patients with SpA (SpA; n = 51) and a healthy control (HC; n = 23) group. Analysis of YF specific neutralizing antibodies test (PRNT), along with YF viremia and the levels of serum chemokines, cytokines, and growth factors were performed at distinct time points (D0, D3, D4, D5, D6, D7, D14, and D28). The BASDAI scores were evaluated at D0 and D180. Data demonstrated that overall, the SpA group presented lower PRNT titers and seropositivity rates as compared to the HC group (GeoMean = 112 vs. 440; 73% vs. 96%, respectively). In SpA subgroup analyses, previous biological DMARDs (BIO-IT) led to a lower PRNT titers (BIO-IT 79, 95% CI [39-150] vs. without biological DMARDs [non-BIO-IT] 159, 95% CI [94-267], p < 0.001). The non-BIO-IT group achieved a response similar to the HC group (81% vs. 96%, p = 0.112), whereas the BIO-IT group had a lower seroconversion rate (64% vs. 96% HC, p = 0.007). The BASDAI was not associated with PRNT levels and did not change after 6 months of follow-up. No differences in YF viremia were observed amongst subgroups. Higher baseline levels of serum biomarkers were observed in the BIO-IT group vs. the non-BIO-IT group, as well as in those with a BASDAI ≥ 4 vs. those with a BASDAI < 4. Increasing levels of several biomarkers were observed in SpA, especially in the BIO-IT and BASDAI ≥ 4 subgroups throughout the timeline kinetics, with impairment/disturbance in the IFN-γ/IL-10 axis around the peak of viremia (D5). Altogether, these findings suggested that the use of biological DMARDs impacts the response to the 17DD-YF vaccine, even after planned washout. Therefore, previous biological DMARD therapy, the inflammatory status prior vaccination, and impairment of the IFN-γ/IL-10 axis at the peak of viremia may determine the immunogenicity of 17DD-YF vaccination in patients with SpA.

Serum biomarker profile orchestrating the seroconversion status of patients with autoimmune diseases upon planned primary 17DD Yellow fever vaccination.

The present study aimed to investigate whether the serum biomarkers of immune response orchestrate the seroconversion status in patients with autoimmune diseases (AID) upon planned primary 17DD-YF vaccination. For this purpose a total of 161 individuals were enrolled in a prospective study, including patients with Rheumatoid Arthritis (RA = 38), Spondyloarthritis (SpA = 51), Systemic Lupus Erythematosus (SLE = 21) and Sjögren's Syndrome (SS = 30) along with a group of healthy controls (HC = 21). Analysis of plaque reduction neutralization test (PRNT) titers and seropositivity rates along with the 17DD-YF viremia and serum biomarkers were carried out at distinct time points (D0/D3-4/D5-6/D7/D14-28). The results demonstrated an overall lower PRNT titer and seropositivity rate (170 vs. 448; 77 vs. 95%) in AID as compared to HC, especially in SpA and SLE subgroups. No significant differences were observed in the viremia levels amongst groups. In general, a more prominent serum biomarker response was observed in AID as compared to HC, throughout the timeline kinetics. Remarkably, AID/PRNT(-) exhibited higher levels of several biomarkers at baseline as compared to AID/PRNT+. Moreover, while AID/PRNT(+) exhibited earlier increase in serum biomarkers at D3-4/D5-6, the AID/PRNT(-) displayed higher response at later time points (D7/D14-D28). Of note, a synchronic increase of IFN-γ at the peak of viremia (D5-6) was observed in HC and AID/PRNT(+) groups, whereas a later asynchronous IFN-γ response was reported for AID/PRNT(-) at D7. The biomarker profile tends to deflate at post-vaccination timeline, highlighting a putative immunomodulatory effect of live attenuated 17DD-YF vaccine in AID/PRNT(+), but not in AID/PRNT(-). Altogether these data suggested that inflammatory status prior vaccination, low IFN-γ at viremia peak and the occurrence of asynchronous biomarker storm after 17DD-YF vaccination may orchestrate the lack of neutralizing antibody response γ.

Planned Yellow Fever Primary Vaccination Is Safe and Immunogenic in Patients With Autoimmune Diseases: A Prospective Non-interventional Study.

Yellow Fever (YF) vaccination is suggested to induce a large number of adverse events (AE) and suboptimal responses in patients with autoimmune diseases (AID); however, there have been no studies on 17DD-YF primary vaccination performance in patients with AID. This prospective non-interventional study conducted between March and July, 2017 assessed the safety and immunogenicity of planned 17DD-YF primary vaccination in patients with AID. Adult patients with AID (both sexes) were enrolled, along with healthy controls, at a single hospital (Vitória, Brazil). Included patients were referred for planned vaccination by a rheumatologist; in remission, or with low disease activity; and had low level immunosuppression or the attending physician advised interruption of immunosuppression for safety reasons. The occurrence of AE, neutralizing antibody kinetics, seropositivity rates, and 17DD-YF viremia were evaluated at various time points (day 0 (D0), D3, D4, D5, D6, D14, and D28). Individuals evaluated (n = 278), including patients with rheumatoid arthritis (RA; 79), spondyloarthritis (SpA; 59), systemic sclerosis (8), systemic lupus erythematosus (SLE; 27), primary Sjögren's syndrome (SS; 54), and healthy controls (HC; 51). Only mild AE were reported. The frequency of local and systemic AE in patients with AID and HC did not differ significantly (8 vs. 10% and 21 vs. 32%; p = 1.00 and 0.18, respectively). Patients with AID presented late seroconversion profiles according to kinetic timelines of the plaque reduction neutralization test (PRNT). PRNT-determined virus titers (copies/mL) [181 (95% confidence interval (CI), 144-228) vs. 440 (95% CI, 291-665), p = 0.004] and seropositivity rate (78 vs. 96%, p = 0.01) were lower in patients with AID after 28 days, particularly those with SpA (73%) and SLE (73%), relative to HC. The YF viremia peak (RNAnemia) was 5-6 days after vaccination in all groups. In conclusion, consistent seroconversion rates were observed in patients with AID and our findings support that planned 17DD-YF primary vaccination is safe and immunogenic in patients with AID.