{"doi":"10.1002/ajh.26380","title":"Distinct neutralization profile of spike variants by antibodies induced upon <scp>SARS‐CoV</scp>‐2 infection or vaccination","abstract":"To The Editor: Emerging SARS-CoV-2 variants have raised concerns about levels of immunity to variant Spike proteins after prior SARS-CoV-2 infection or vaccination. Here, we report distinct cross-reactivity of Wuhan-HA-1 (WA1)-induced antibodies upon BNT162b2 mRNA vaccination and SARS-CoV-2 infection. We show that neutralizing antibodies against WA1 strongly correlate with Delta neutralization, and that SARS-CoV-2 infection-induced antibodies have better neutralization capability for the Delta variant compared to vaccination. We measured the magnitude and breadth of Spike antibody responses against the original WA1 and three variants (Alpha [B.1.1.7], Beta [B.1.351], and Delta [B.1.617.2]) of SARS-CoV-2 in three cohorts: (i) SARS-CoV-2 naïve recipients of two doses of BNT162b2 mRNA (Pfizer/BioNTech) vaccine (day 90 post first dose; n = 55); (ii) COVID-19 convalescent patients who received the first dose of the BNT162b2 mRNA vaccine at 6–10 months postsymptom onset (day 90 post first dose; n = 5); (iii) COVID-19 convalescent patients (n = 23) at peak postinfection at a median of 2 months postsymptom onset. We examined the levels and breadth of anti-Spike antibodies and their neutralizing ability against WA1 and the variants Alpha, Beta, and Delta, which differ by one to three amino acids (AA) within the receptor-binding domain (RBD) (Figure 1A). The study participants including patients and volunteers are described in NCT04408209 and NCT04743388. CoV-2 naïve volunteers and COVID-19 convalescent patients received two doses of BNT162b2 mRNA vaccine at day 1 and 21, respectively.1 The convalescent vaccine recipients received first dose at 6–10 months postsymptom onset.1 SARS-CoV-2-infected patients analyzed at a median of 2 months postsymptom onset have been described.2, 3 In-house ELISA using a panel of purified Spike-RBD proteins (AA 319–525) were detailed elsewhere.2, 4, 3 Neutralization was performed using a pseudotyped HIVNLΔEnv-Nanoluc assay5, 6 carrying a panel of Spike (AA 1–1254) proteins as described.2, 4, 3 Statistical analyses were performed using analysis of variance and Spearman correlation (GraphPad Prism Version 9.0.2 X; GraphPad Software, Inc.). All three cohorts showed robust humoral response to WA1 Spike-RBD. Similar antibody levels were detected in the naïve BNT162b2 mRNA vaccine recipients at day 90 and in the COVID-19 convalescent patients (2 months postinfection). A 12-fold higher Ab level was detected in the convalescent vaccinees,1 as a result of a strong anamnestic response in this cohort1, 7-9 (Figure 1B–D). Compared to the responses against WA1, the vaccine-induced antibodies showed significantly lower recognition of Alpha and Delta Spike-RBD and greatly reduced binding of Beta Spike-RBD in the naïve vaccines (Figure 1B). In contrast, the Spike-RBD antibodies in the SARS-CoV-2 convalescent vaccine recipients (Figure 1C) showed similar strong binding to Beta and Delta indicating some improved breadth. Despite the increased humoral responses, recognition of Beta Spike-RBD was significantly reduced (Figure 1C). We further compared the anti-Spike-antibody breadth in a cohort of COVID-19 convalescent patients (Figure 1D). We noted a similar ranking of responses as in the cohort of naïve vaccine recipients with reduced recognition of Delta and Beta Spike-RBD. Together, our data suggest a strong benefit of vaccination for COVID-19 convalescent patients. Our data further point to two AA changes (K417N and E484K; Figure 1A), which play a key role for RBD recognition. These data mirror our recent findings from nonhuman primates which received WA1 Spike-based DNA vaccines.4 Importantly, increased Spike-RBD antibody magnitude cannot compensate for this. Thus, a booster vaccination including different variants may be beneficial and should be considered. Next, we tested the neutralizing capability of the Spike antibodies in the different groups (Figure 1E–G). Sera were tested for their ability to neutralize infection","journal":"American Journal of Hematology","year":2021,"id":192381,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":336801,"name":"Evangelos Terpos","orcid":"0000-0001-5133-1422","position":1,"is_corresponding":false},{"id":672941,"name":"Mahesh Agarwal","orcid":"0009-0003-1988-1629","position":2,"is_corresponding":false},{"id":631960,"name":"Vangelis Karalis","orcid":"0000-0003-0492-0712","position":3,"is_corresponding":false},{"id":258856,"name":"Jenifer Bear","orcid":"0000-0001-5065-6081","position":4,"is_corresponding":false},{"id":270587,"name":"Robert Burns","orcid":"0000-0001-5334-3486","position":5,"is_corresponding":false},{"id":336804,"name":"Xintao Hu","orcid":"0000-0002-6552-9357","position":6,"is_corresponding":false},{"id":759433,"name":"Demetrios G. Papademetriou","orcid":"0000-0001-6228-4318","position":7,"is_corresponding":false},{"id":336807,"name":"Ioannis Ntanasis‐Stathopoulos","orcid":"0000-0002-6328-9783","position":8,"is_corresponding":false},{"id":621576,"name":"Ioannis P. Trougakos","orcid":"0000-0002-6179-2772","position":9,"is_corresponding":false},{"id":228859,"name":"Meletios Α. Dimopoulos","orcid":"0000-0001-8990-3254","position":10,"is_corresponding":false},{"id":258860,"name":"George N. Pavlakis","orcid":"0000-0002-4027-4036","position":11,"is_corresponding":false},{"id":258859,"name":"Barbara K. Felber","orcid":"0000-0001-8925-8128","position":12,"is_corresponding":false},{"id":338297,"name":"Margherita Rosati","orcid":null,"position":0,"is_corresponding":true}],"reference_count":18,"raw_metadata":null,"created_at":"2026-07-18T23:49:43.496702Z","pmid":"34674297","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}