{"doi":"10.1002/ajh.26887","title":"<scp>XBB</scp>.1.5 neutralizing antibodies upon bivalent <scp>COVID</scp>‐19 vaccination are similar to <scp>XBB</scp> but lower than <scp>BQ</scp>.1.1","abstract":"The COVID-19 virus has evolved significantly from the ancestral WA1/2020 strain over the past 3 years with new sublineages, subvariants, and recombinant strains emerging and causing new waves of infections.1 During 2022, the Omicron B.1.1.529 sublineages have been spreading world-wide and a recent emerging rapidly spreading XBB.1.5 variant has been reported (www.gisaid.org). This prompted the analysis of vaccine induced neutralizing antibody (NAb) to evaluate protective efficacy to the newly circulating variants. Our results show lower but detectable neutralizing activity to the newer circulating variants including XBB.1.5, suggesting a continuing benefit of the current bivalent (WA1/BA.5) vaccine. Because anti-Spike immunity is known to decline overtime, bivalent booster vaccinations in previously boosted individuals or after BA.5 breakthrough infection are justified because they increase immunity and enhance the probability to neutralize further evolving variants. Due to continuing erosion of immunity by the newly emerging variants, the timely updating of future booster vaccines remains one of the most important issues in the fight against COVID. Although different COVID-19 proteins contribute to SARS-CoV-2 pathogenesis, the different evolving Spike variants are of particular interest because they facilitate cell entry via the ACE2 receptor protein, an interaction that directly affects virus transmissibility and impacts on the vaccine efficacy. The first generation of COVID-19 vaccines used the WA1/2020 Spike protein. We and others reported that the vaccine-induced immunity provided reduced neutralization of the Omicron BA.1.529.1 subvariants BA.4 and BA.5, which share identical Spike proteins (Supplemental Methods). The BA.4/5 Spike differs from the ancestral WA1 Spike at 18 amino acids (AA) located within Receptor Binding Domain (RBD) including the mutations L452R, F486V, R493Q (Figure 1A). The second generation COVID-19 vaccine comprising a bivalent mRNA vaccine including both the ancestral WA1 and Omicron BA.5 Spike proteins, improved neutralization of BA.4/5. However, the recent emergence of additional Omicron sublineages raised concerns about the breadth and strength of the bivalent vaccine-induced NAb. Of concern are the multiple changes in RBD located in key interaction sites with the ACE2 receptor. The RBD of the BQ.1 sublineage has additional mutations at positions R346T, K444T, and N460K. The RBDs of XBB and XBB1.5 share additional mutations at L368I, V445P, N460K, and F490S and differ by an additional mutation F486S (XBB) and F486P (XBB.1.5), a rarely seen AA change emerged late in 2022.2, 3 The rapidly spreading XBB.1.5 alerted the medical community about possible impact on the protective efficacy of the NAb induced by the current bivalent COVID-19 vaccine. In this part of the NCT04743388 study, we evaluated the NAb magnitude and breadth targeting ancestral WA1, different Omicron sublineages, including the recently emerging XBB.1.5, in different SARS CoV-2 vaccinated (monovalent or bivalent) cohorts and a COVID-19 breakthrough cohort in Greece. Major inclusion criteria included: (i) age above 18 years; (II) ability to sign the informed consent form and (iii) eligibility for vaccination, according to the national program for COVID-19 vaccination. Major exclusion criteria included the presence of: (i) autoimmune disorder under immunosuppressive therapy; (ii) active malignant disease and (iii) end-stage renal disease, as previously described.4 The BA.1/BA.2 sublineages circulating during spring 2022 in Greece were largely replaced by BA.5 in the summer5 (Figure 1B). The more recent circulating variants include BQ.1.1 and the newly introduced XBB and XBB.1.5.5 The median age of the participants (n = 79) was 56.5 years (range 22–100), whereas 28 (35.4%) were males and the median body mass index was 25.6 kg/m2 (range 17.6–35.9). Ten (12.6%) individuals had hypercholesterolemia and 21 (26.5%) had hypertension. The part","journal":"American Journal of Hematology","year":2023,"id":336952,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9575,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","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":338297,"name":"Margherita Rosati","orcid":null,"position":2,"is_corresponding":false},{"id":336807,"name":"Ioannis Ntanasis‐Stathopoulos","orcid":"0000-0002-6328-9783","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":1067897,"name":"Stamatia Skourti","orcid":"0000-0001-9501-3143","position":6,"is_corresponding":false},{"id":1067898,"name":"Panagiotis Malandrakis","orcid":"0000-0002-4673-171X","position":7,"is_corresponding":false},{"id":621576,"name":"Ioannis P. Trougakos","orcid":"0000-0002-6179-2772","position":8,"is_corresponding":false},{"id":228859,"name":"Meletios Α. Dimopoulos","orcid":"0000-0001-8990-3254","position":9,"is_corresponding":false},{"id":258860,"name":"George N. Pavlakis","orcid":"0000-0002-4027-4036","position":10,"is_corresponding":false},{"id":258859,"name":"Barbara K. Felber","orcid":"0000-0001-8925-8128","position":11,"is_corresponding":false},{"id":751999,"name":"Santhi Devasundaram","orcid":"0000-0002-2803-7118","position":0,"is_corresponding":true}],"reference_count":9,"raw_metadata":null,"created_at":"2026-07-19T01:10:21.947540Z","pmid":"36810791","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":[]}