RESUMEN
AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSPatients with cancer, especially haematological cancer, are at increased risk for breakthrough COVID-19 infection. However, so far, a predictive biomarker that can assess compromised vaccine-induced anti-SARS-CoV-2 immunity in cancer patients has not been proposed. MethodsHere, we employed machine learning approaches to identify a biomarker signature based on blood cytokine and growth factors linked to vaccine response from 199 cancer patients receiving BNT162b2 vaccine. ResultsWe show that C-reactive protein (CRP; general marker of inflammation), interleukin (IL)-15 (a pro-inflammatory cytokine), IL-18 (interferon-gamma inducing factor), and placental growth factor (an angiogenic cytokine) can correctly classify patients with a diminished vaccine response assessed at day 49 with >80% accuracy. Amongst these, CRP showed the highest predictive value for poor response to vaccine administration. Importantly, this unique signature of vaccine response was present at different studied timepoints both before and after vaccination and was not majorly affected by different anti-cancer treatments. ConclusionWhile we propose a blood-based signature of cytokines and growth factors that can be employed in identifying cancer patients at continued risk of COVID-19, our data also importantly suggest that such a signature could reflect the inherent make-up of some cancer patients who are also refractive to immunotherapy.
RESUMEN
As solid organ recipients are at high risk of severe COVID-19 and respond poorly to primary SARS-CoV-2 mRNA vaccination, they have been prioritized for booster vaccination. However, an immunological correlate of protection has not been identified in this vulnerable population. We conducted a prospective monocentric cohort study of 65 kidney transplant recipients who received three doses of SARS-CoV-2 BNT162b2 mRNA vaccination. Associations between symptomatic breakthrough infection (BTI) and vaccine responses, patient demographic and clinical characteristics were explored. Symptomatic COVID-19 was diagnosed in 32% of kidney transplant recipients during a period of six months after the administration of the third vaccine dose. During this period, SARS-CoV-2 delta and omicron were the dominant variants in the general population. Univariate analyzes identified avidity of SARS-CoV-2 receptor binding domain (RBD) binding IgG, neutralizing antibodies and SARS-CoV-2 S2 domain-specific IFN-{gamma} responses as correlates of protection against BTI. Some demographic and clinical parameters correlated with vaccine responses, but none correlated with the risk of BTI. In multivariate analysis, the risk of BTI was best predicted by neutralizing antibody and S2-specific IFN-{gamma} responses, adjusting for age, graft function and mycophenolate mofetil use. In conclusion, both antibody and T cell responses predict the risk of BTI in kidney transplant recipients who received three doses of SARS-CoV-2 mRNA vaccine. T cell responses may help compensate for the suboptimal antibody response to vaccination in this vulnerable population. One Sentence SummaryAntibody and T cell responses to booster SARS-CoV-2 vaccination predict the risk of symptomatic breakthrough infection in kidney transplant recipients
RESUMEN
1BackgroundThe use of fractional dose regimens of COVID-19 vaccines has the potential to accelerate vaccination rates in low-income countries. Dose-finding studies of the mRNA vaccine BNT162b2 (Pfizer-BioNTech) have suggested that a fractional dose induces comparable antibody responses to the full, licensed dose in people below 55 years old. Here, we report the safety and immunogenicity of a fractional dose regimen of the BNT162b2 vaccine. MethodsREDU-VAC is a participant-blinded, randomised, phase 4, multicentre, non-inferiority study investigating safety, reactogenicity and immunogenicity of BNT162b2. Adults aged between 18 and 55 years, without uncontrolled co-morbidities, either previously infected or infection naive, were eligible and recruited at five sites across Belgium. Participants were randomly assigned to receive 20{micro}g/20{micro}g (fractional dose) or 30{micro}g/30{micro}g (full dose) of BNT162b2, administered intra-muscularly at a three-week interval. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-RBD IgG titres at 28 days post second dose between the reduced and the full dose regimens. The reduced dose was considered non-inferior to the full dose if the lower limit of the two-sided 95% CI of the GMR was greater than 0.67. The primary analysis was done on the per-protocol population, including infection naive participants only. FindingsBetween April 19 and April 23, 2021, 145 participants were enrolled in the study and randomized, of whom 141 were vaccinated and reached the primary endpoint. Participants were mostly female (69.5%), of European origin (95%), with a mean age of 40.4 years (SD 7.9). At 28 days post second dose, the geometric mean titre (GMT) of SARS-CoV-2 anti-RBD IgG of the reduced dose regimen (1,705 BAU/mL) was not non-inferior to the full dose regimen (2,387 BAU/mL), with a GMR of 0.714 (two-sided 95% CI 0.540-0.944). No serious adverse events occurred. ConclusionsWhile non-inferiority of the reduced dose regimen was not demonstrated, the SARS-CoV-2 anti-RBD IgG titre was only moderately lower than that of the full dose regimen and, importantly, still markedly higher than the reported antibody response to the licensed adenoviral vector vaccines. These data suggest that reduced doses of the BNT162b2 mRNA vaccine may offer additional benefit as compared to the vaccines currently in use in most low and middle-income countries, warranting larger immunogenicity and effectiveness trials. The trial is registered at ClinicalTrials.gov (NCT04852861).
RESUMEN
We report the levels of neutralising antibodies against Wuhan, Delta and Omicron variants in healthy individuals pre-infected or not with SARS-CoV-2 and immunized with three doses of the BNT162b2 vaccine. Our observations support the rapid administration of a booster vaccine dose to prevent infection and disease caused by Omicron.
RESUMEN
BackgroundResidents of nursing homes (NH) are at high risk of COVID-19 related morbidity and death and may respond poorly to vaccination because of old age and frequent comorbidities. MethodsForty residents and forty staff members either naive or previously infected with SARS-CoV-2 were recruited in two NH in Belgium before immunization with two doses of 30{micro}g BNT162b2 mRNA vaccine at day 0 and day 21. Binding antibodies (Ab) to SARS-CoV-2 receptor binding domain (RBD), spike domains S1 and S2, RBD Ab avidity, and neutralizing Ab against SARS-CoV-2 wild type and B.1.351 variant were assessed at days 0, 21, 28, and 49. ResultsSARS-CoV-2 naive residents had lower Ab responses to BNT162b2 mRNA vaccination than naive staff. These poor responses involved lower levels of IgG to all domains of the vaccine antigen, lower avidity of RBD IgG, and lower levels of Ab neutralizing the vaccine strain. No naive resident had detectable neutralizing Ab to the B.1.351 variant. High and comparable Ab responses were observed in residents and staff previously infected with SARS-CoV-2. Clustering analysis revealed that poor vaccine responders not only included naive residents but also naive staff, emphasizing the heterogeneity of responses to mRNA vaccination in the general population. ConclusionsThe poor Ab responses to mRNA vaccination observed in infection naive residents and in some naive staff members of NH suggest suboptimal protection against breakthrough infection, especially with variants of concern. Adapted vaccination regimens may be needed to provide optimal protection against COVID-19 to vulnerable populations. SummaryPoor antibody responses to COVID-19 mRNA vaccination were observed in SARS-CoV-2 infection naive residents and some naive staff members of nursing homes. This suggests suboptimal protection against breakthrough infection, especially with variants of concern, and the need for adapted vaccination regimens.
