Loss of Pfizer (BNT162b2) Vaccine-Induced Antibody Responses Against the SARS-CoV-2 Omicron Variant in Adolescents and Adults

The Pfizer-BioNTech (BNT162b2) mRNA vaccine induces potent immunity against SARS-CoV-2 in adults and provides strong protection against the original SARS-CoV-2 Wuhan strain. Newly emerging variants and gaps in vaccine coverage threaten this protection. The B.1.1.529 variant (Omicron) emerged in November of 2021 and caused concern, given the high number of mutations in the spike protein. Recent studies have shown that vaccinated adults have severely reduced neutralization titers against the Omicron variant. While children have been relatively spared by the ongoing pandemic, increasing case numbers and hospitalizations are now evident among children. Thus, it is essential to better understand the magnitude and breadth of vaccine-induced immunity in children against circulating viral variant of concerns (VOCs), including the Omicron variant. Here we compare the magnitude and breadth of humoral immune responses in adolescents and adults one month after the two dose Pfizer (BNT162b2) vaccination, using a combination of an electro-chemiluminescent multiplex assay (ELICA-MSD) to measure antibody binding titers and live virus neutralization assay (FRNT50) to quantitate neutralization potential against a panel of VOCs. We find that adolescents, median age 13 (range 11-16), demonstrated more robust binding antibody and neutralization responses against the WT SARS-CoV-2 virus spike contained in the vaccine as compared to adults, median age 35 (range 27-55). The quality of the antibody responses against VOCs in adolescents were very similar to adults, with modest changes in binding and neutralization of Beta, Gamma, Delta and Mu. In comparison, a significant reduction of binding titers and a striking lack of neutralization was observed against the newly emerging Omicron variant for both adolescents and adults. Overall, our data shows that two doses of BNT162b2 induce a higher magnitude and more potent functional antibody responses in adolescents as compared to adults, and that a comparable breadth of the antibody repertoire develops against VOCs. Strikingly, vaccine-induced antibody responses one-month post-vaccination were almost universally unable to neutralize the recently emergent Omicron variant, in both adolescents and adults. These data suggest that a two-dose BNTb162b vaccine series may be insufficient to protect against the Omicron variant.Funding: This work was supported in part by grants (NIH P51 OD011132, 3U19AI057266-17S1, 1U54CA260563, HHSN272201400004C, NIH/NIAID CEIRR under contract 75N93021C00017 to Emory University) from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), by The Oliver S. and Jennie R. Donaldson Charitable Trust, Emory Executive Vice President for Health Affairs Synergy Fund award, the Georgia Research Alliance, the Pediatric Research Alliance Center for Childhood Infections and Vaccines and Children’s Healthcare of Atlanta, the Emory-UGA Center of Excellence for Influenza Research and Surveillance (Atlanta, GA USA), COVID-Catalyst-I3 funds from the Woodruff Health Sciences Center and Emory School of Medicine, Woodruff Health Sciences Center 2020 COVID-19 CURE Award.Declaration of Interest: E.J.A. has consulted for Pfizer, Sanofi Pasteur, Janssen, and Medscape, and his institution receives funds to conduct clinical research unrelated to this manuscript from MedImmune, Regeneron, PaxVax, Pfizer, GSK, Merck, Sonfi- Pasteur, Janssen, and Micron. He also serves on data and safety monitoring boards for Kentucky BioProcessing, Inc., and Sanofi Pasteur. His institution has also received funding from NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines. C.A.R.’s institution has received funding to conduct clinical research unrelated to this manuscript from BioFire Inc., GSK, MedImmune, Micron, Merck, Novavax, PaxVax, Regeneron, and Sanofi Pasteur. She is co-inventor of patented RSV vaccine technology unrelated to this manuscript, which has been licensed to Meissa Vaccines, Inc. Her institution has received funding from NIH, Moderna, Pfizer, and Janssen to conduct clinical trials of COVID-19 vaccines. M.S.S. serves as an advisor for Moderna and Ocugen. Remaining authors do not have any conflict of interest.Ethical Approval: All studies were approved by the Emory University (IRB Study 00000723) and Washington University (IRB Study number 202012081)Institutional Review Board approvals, for adolescent and adult participants, respectively. Written informed consent and assent were obtained from all participants, as appropriate for age.