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Rapid Decline in Vaccine-Boosted Neutralizing Antibodies Against SARS-CoV-2 Omicron Variant

2022; RELX Group (Netherlands); Linguagem: Inglês

10.2139/ssrn.4061187

1556-5068

Kirsten E. Lyke, Robert L. Atmar, Clara Domínguez Islas, Christine M. Posavad, Daniel Szydlo, Rahul PaulChourdhury, Meagan E. Deming, Amanda Eaton, Lisa A. Jackson, Angela Ramon Branche, Hana M. El Sahly, Christina A. Rostad, Judith M. Martin, Christine Johnston, Richard Rupp, Mark J. Mulligan, Rebecca C. Brady, Robert W. Frenck, Martín Bäcker, Angelica C Kottkamp, Tara M. Babu, Kumaravel Rajakumar, Srilatha Edupuganti, David Dobrzynski, Rhea N. Coler, Janet I. Archer, Sonja Crandon, Jillian A. Zemanek, Elizabeth R. Brown, Kathleen M. Neuzil, David S. Stephens, Diane J. Post, Seema Nayak, Mehul S. Suthar, Paul C. Roberts, John H. Beigel, David C. Montefiori,

COVID-19 Clinical Research Studies

The Omicron variant of SARS-CoV-2 exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. Little is known about the durability of vaccine-boosted omicron neutralizing antibodies and the potential impact of boosting with heterologous vaccine modalities. We assessed the magnitude and short-term durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.S vaccines. Using pseudovirus and live virus neutralization assays, all prime-boost combinations substantially increased the neutralization titers to Omicron although the boosted titers declined rapidly within 2 months from the peak response compared to boosted titers against the prototypic D614G variant. Boosted Omicron neutralization titers were substantially higher for homologous mRNA vaccine boosting, and for heterologous mRNA and Ad26.COV2.S vaccine boosting, compared to homologous Ad26.COV2.S boosting. Homologous mRNA vaccine boosting generated nearly equivalent neutralizing activity against Omicron subvariants BA.1, BA.2 and BA.3. These results have implications for boosting requirements to protect against Omicron and future variants of SARS-CoV-2.Trial Registration: Clinical Trials.gov number, NCT04889209.Funding Information: The trial was sponsored and primarily funded by the Infectious Diseases Clinical Research Consortium through the National Institute for Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH), under award numbers UM1AI48372, UM1AI148373, UM1AI148450, UM1AI148452, UM1AI148573, UM1AI148574, UM1AI148575, UM1AI148576, UM1AI148684, UM1 AI148689 and with support from the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVICs) contract 75N93019C00050 and NIH Vaccine Research Center. Funding for the Suthar laboratory included: NIH P51 OD011132, 3U19AI057266-17S1, 1U54CA260563, HHSN272201400004C, NIH/NIAID CEIRR under contract 75N93021C00017 to Emory University) from NIAID and Emory School of Medicine, Woodruff Health Sciences Center 2020 COVID-19 CURE Award.Conflict of Interests: RLA, CPDI, CMP, DS, RP, MED, AE, HME, RER, MB, ACK, TMB, DD, RNC, JLA, SC, JAZ, SUN, ERB, DJP, and SUN report no competing interests. KEL receives grant awards from Pfizer Inc. COVID-19 vaccine research. LAJ's institution receives grant funding from NIH and CDC for vaccine-related assessments, including those of COVID-19 vaccines. ARB has grant funding from Pfizer, Janssen, Merck and Cyanvac for non-COVID-19-related work and serves as a consultant for GSK and Janssen. CAR's institution has received funds to conduct clinical research from the National Institutes of Health, CDC, BioFire Inc, Genentech, GSK, Janssen, MedImmune, Merck, Micron, Moderna, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur. She is co-inventor of patented RSV vaccine technology, which has been licensed to Meissa Vaccines, Inc. JMM has served as a consultant for Merck, Sharp and Dohme for non-Covid- 14 related work. CJ receives funding from the Bill and Melinda Gates Foundation, NIH and CDC, consults for Gilead and Abbvie, serves on a DSMB for MedPace, and receives royalties from UpToDate. MJM has laboratory research and clinical trials contracts for vaccines or MAB vs SARS-CoV-2 with Lilly, Pfizer (exclusive of the current work), and Sanofi; personal fees for Scientific Advisory Board service from Merck, Meissa Vaccines, Inc. and Pfizer. RCB receives funding for vaccine trials from Path Nipah and Pfizer. RWF receives funding to perform clinical trials from Pfizer, Moderna, Astra Zeneca and Emergent Health, and he serves on advisory boards for Johnson & Johnson, Merck, Sanofi Pasteur and Seqirus. SE receives funding to her institution from Sanofi Pasteur for a non-COVID-19 vaccine study. KMN holds a grant from Pfizer, without salary support, for a COVID-19 vaccine study, and salary support from the National Institutes of Health (NIH) for work on multiple COVID-19 vaccine trials. DSS is supported by grant awards from NIH/NIAID. PCR and JHB report a pending U.S. Patent Application No. 63/025,918 entitled "Coronavirus RNA vaccines and methods of use" DCM receives funding from NIH and Moderna for laboratory studies of COVID-19 vaccine antibody responses. MSS receives funding from Moderna Inc. and Ocugen. DM receives funding from Moderna Inc.Ethical Approval: Ethics Approval Statement: Ethical approval for the study was given by the Advarra IRB (www.advarra.com) of Columbia, MD (OHRP FWA: 00023875) with additional site-specific approvals provided.