{"doi":"10.1101/2022.06.22.22276362","title":"Immune Correlates Analysis of the PREVENT-19 COVID-19 Vaccine Efficacy Clinical Trial","abstract":"Abstract 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 3 rd percentile, 6934 is the 97.5 th 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 5 th percentile, 7230 the 97.5 th 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.","journal":"medRxiv","year":2022,"id":296926,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9374,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":331739,"name":"Yunda Huang","orcid":"0000-0003-1546-6172","position":1,"is_corresponding":false},{"id":305708,"name":"David Benkeser","orcid":"0000-0002-1019-8343","position":2,"is_corresponding":false},{"id":539332,"name":"Lindsay N. 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