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In the randomized, placebo-controlled PREVENT-19 phase 3 trial conducted in the U.S. and Mexico of the NVX-CoV2373 adjuvanted, recombinant spike protein nanoparticle vaccine, anti-spike binding IgG concentration (spike IgG) and pseudovirus 50% neutralizing antibody titer (nAb ID50) measured two weeks after two doses were assessed as correlates of risk and as correlates of protection against PCR-confirmed symptomatic SARS-CoV-2 infection (COVID- 19). These immune correlates analyses were conducted in the U.S. cohort of baseline SARS- CoV-2 negative per-protocol participants using a case-cohort design that measured the antibody markers from all 12 vaccine recipient breakthrough COVID-19 cases starting 7 days post antibody measurement and from 639 vaccine recipient non-cases (Mexico was excluded due to zero breakthrough cases with the efficacy data cut-off date April 19, 2021). In vaccine recipients, the baseline risk factor-adjusted hazard ratio of COVID-19 was 0.36 (95% CI: 0.20, 0.63), p<0.001 (adjusted p-0.005) per 10-fold increase in IgG spike concentration and 0.39 (0.19, 0.82), p=0.013 (adjusted p=0.030) per 10-fold increase in nAb ID50 titer. At spike IgG concentration 100, 1000, and 6934 binding antibody units/ml (100 is the 3rd percentile, 6934 is the 97.5th percentile), vaccine efficacy to reduce the probability of acquiring COVID-19 at 59 days post marker measurement was 65.5% (95% CI: 23.0%, 90.8%), 87.7% (77.7%, 94.4%), and 94.8% (88.0%, 97.9%), respectively. At nAb ID50 titers of 50, 100, 1000, and 7230 IU50/ml (50 is the 5th percentile, 7230 the 97.5th percentile), these estimates were 75.7% (49.8%, 93.2%), 81.7% (66.3%, 93.2%), 92.8% (85.1%, 97.4%) and 96.8% (88.3%, 99.3%). The same two antibody markers were assessed as immune correlates via the same study design and statistical analysis in the mRNA-1273 phase 3 COVE trial (except in COVE the markers were measured four weeks post dose two). Spike IgG levels were slightly lower and nAb ID50 titers slightly higher after NVX-CoV2373 than after mRNA-1273 vaccination. The strength of the nAb ID50 correlate was similar between the trials, whereas the spike IgG antibodies appeared to correlate more strongly with NVX-CoV2373 in PREVENT-19, as quantified by the hazard ratio and the degree of change in vaccine efficacy across antibody levels. However, the relatively few breakthrough cases in PREVENT-19 limited the ability to infer a stronger correlate. The conclusion is that both markers were consistent correlates of protection for the two vaccines, supporting potential cross-vaccine platform applications of these markers for guiding decisions about vaccine approval and use.
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Anti-spike IgG binding antibody, anti-receptor binding domain IgG antibody, and pseudovirus neutralizing antibody measurements four weeks post-vaccination were assessed as correlates of risk of moderate to severe-critical COVID-19 outcomes through 83 days post-vaccination and as correlates of protection following a single dose of Ad26.COV2.S COVID-19 vaccine in the placebo-controlled phase of ENSEMBLE, an international, randomized efficacy trial. Each marker had evidence as a correlate of risk and of protection, with strongest evidence for 50% inhibitory dilution (ID50) neutralizing antibody titer. The outcome hazard ratio was 0.49 (95% confidence interval 0.29, 0.81; p=0.006) per 10-fold increase in ID50; vaccine efficacy was 60% (43, 72%) at nonquantifiable ID50 (< 2.7 IU50/ml) and rose to 89% (78, 96%) at ID50 = 96.3 IU50/ml. Comparison of the vaccine efficacy by ID50 titer curves for ENSEMBLE-US, the COVE trial of the mRNA-1273 vaccine, and the COV002-UK trial of the AZD1222 vaccine supported consistency of the ID50 titer correlate of protection across trials and vaccine types.
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Objective To study the composition and concentration of atmospheric particulate pollutants in four seasons in the industrial and clean living areas， and to provide a scientific basis for the strategy of controlling industrial pollution and atmospheric environment. Methods An industrial area dominated by the automobile industry in Shanghai and a relatively clean living area were selected. Samples were collected simultaneously in both areas and continuously for 7 days in the middle of each season. The composition and concentration of PM2.5 were determined， and the ecological risk of heavy metals in PM2.5 was evaluated by the potential ecological risk index method. Results We found PM2.5 concentration was associated with seasonal changes. The PM2.5 concentration in living areas was the highest in winter， followed by spring， and the lowest in summer. The PM2.5 concentration in industrial areas was the highest in spring， followed by winter， and the lowest in summer. The heavy metals in PM2.5 were the same， including Al， Cr， Mn， Ni， As， Cd， Hg and Pb. The content of Cr， Cd and Pb in PM2.5 in the industrial area is significantly higher than that in the living area. The potential ecological hazard coefficient of PM2.5 heavy metal Cd in the industrial zone was the highest， up to 189.47， and it was the main component of the total potential ecological hazard index of heavy metals. According to the total potential risk grade of heavy metals， the heavy metal Cd in the industrial area had different degrees of ecological harm with seasonal changes. The ecological harm degree of heavy metal Cd was the highest in winter， high in spring and autumn， and low in summer. Conclusion Although the concentration of PM2.5 in the industrial area is not higher than that in the living area， the content of Cr， Cd and Pb in the PM2.5 in the industrial area is significantly higher than that in the living area. The concentration of PM2.5 in the industrial area is mainly related to seasons， industrial production and human factors. The potential ecological harm coefficient of heavy metal Cd in PM2.5 is the highest in comparison with other heavy metals such as Cr， Hg and Pb， and it is the main component of the total potential ecological harm index ofheavy metals.
RESUMO
Objective To study the composition and concentration of atmospheric particulate pollutants in four seasons in the industrial and clean living areas， and to provide a scientific basis for the strategy of controlling industrial pollution and atmospheric environment. Methods An industrial area dominated by the automobile industry in Shanghai and a relatively clean living area were selected. Samples were collected simultaneously in both areas and continuously for 7 days in the middle of each season. The composition and concentration of PM2.5 were determined， and the ecological risk of heavy metals in PM2.5 was evaluated by the potential ecological risk index method. Results We found PM2.5 concentration was associated with seasonal changes. The PM2.5 concentration in living areas was the highest in winter， followed by spring， and the lowest in summer. The PM2.5 concentration in industrial areas was the highest in spring， followed by winter， and the lowest in summer. The heavy metals in PM2.5 were the same， including Al， Cr， Mn， Ni， As， Cd， Hg and Pb. The content of Cr， Cd and Pb in PM2.5 in the industrial area is significantly higher than that in the living area. The potential ecological hazard coefficient of PM2.5 heavy metal Cd in the industrial zone was the highest， up to 189.47， and it was the main component of the total potential ecological hazard index of heavy metals. According to the total potential risk grade of heavy metals， the heavy metal Cd in the industrial area had different degrees of ecological harm with seasonal changes. The ecological harm degree of heavy metal Cd was the highest in winter， high in spring and autumn， and low in summer. Conclusion Although the concentration of PM2.5 in the industrial area is not higher than that in the living area， the content of Cr， Cd and Pb in the PM2.5 in the industrial area is significantly higher than that in the living area. The concentration of PM2.5 in the industrial area is mainly related to seasons， industrial production and human factors. The potential ecological harm coefficient of heavy metal Cd in PM2.5 is the highest in comparison with other heavy metals such as Cr， Hg and Pb， and it is the main component of the total potential ecological harm index ofheavy metals.
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BackgroundIn the Coronavirus Efficacy (COVE) trial, estimated mRNA-1273 vaccine efficacy against coronavirus disease-19 (COVID-19) was 94%. SARS-CoV-2 antibody measurements were assessed as correlates of COVID-19 risk and as correlates of protection. MethodsThrough case-cohort sampling, participants were selected for measurement of four serum antibody markers at Day 1 (first dose), Day 29 (second dose), and Day 57: IgG binding antibodies (bAbs) to Spike, bAbs to Spike receptor-binding domain (RBD), and 50% and 80% inhibitory dilution pseudovirus neutralizing antibody titers calibrated to the WHO International Standard (cID50 and cID80). Participants with no evidence of previous SARS-CoV-2 infection were included. Cox regression assessed in vaccine recipients the association of each Day 29 or 57 serologic marker with COVID-19 through 126 or 100 days of follow-up, respectively, adjusting for risk factors. ResultsDay 57 Spike IgG, RBD IgG, cID50, and cID80 neutralization levels were each inversely correlated with risk of COVID-19: hazard ratios 0.66 (95% CI 0.50, 0.88; p=0.005); 0.57 (0.40, 0.82; p=0.002); 0.42 (0.27, 0.65; p<0.001); 0.35 (0.20, 0.61; p<0.001) per 10-fold increase in marker level, respectively, multiplicity adjusted P-values 0.003-0.010. Results were similar for Day 29 markers (multiplicity adjusted P-values <0.001-0.003). For vaccine recipients with Day 57 reciprocal cID50 neutralization titers that were undetectable (<2.42), 100, or 1000, respectively, cumulative incidence of COVID-19 through 100 days post Day 57 was 0.030 (0.010, 0.093), 0.0056 (0.0039, 0.0080), and 0.0023 (0.0013, 0.0036). For vaccine recipients at these titer levels, respectively, vaccine efficacy was 50.8% (-51.2, 83.0%), 90.7% (86.7, 93.6%), and 96.1% (94.0, 97.8%). Causal mediation analysis estimated that the proportion of vaccine efficacy mediated through Day 29 cID50 titer was 68.5% (58.5, 78.4%). ConclusionsBinding and neutralizing antibodies correlated with COVID-19 risk and vaccine efficacy and likely have utility in predicting mRNA-1273 vaccine efficacy against COVID-19. Trial registration numberCOVE ClinicalTrials.gov number, NCT04470427
