Delphine Planas1, Isabelle Staropoli2, Françoise Porot2, Florence Guivel-Benhassine2, Lynda Handala3, Matthieu Prot4, William-Henry Bolland5, Julien Puech6, Hélène Péré7, David Veyer7, Aymeric Sève8, Etienne Simon-Lorière4, Timothée Bruel9, Thierry Prazuck8, Karl Stefic3, Laurent Hocqueloux8, Olivier Schwartz10. 1. Virus and Immunity Unit, Institut Pasteur, Université Paris Cité, CNRS UMR3569, Paris, France; Vaccine Research Institute, Créteil, France. Electronic address: delphine.planas@pasteur.fr. 2. Virus and Immunity Unit, Institut Pasteur, Université Paris Cité, CNRS UMR3569, Paris, France. 3. INSERM U1259, Université de Tours, Tours, France; CHRU de Tours, National Reference Center for HIV-Associated Laboratory, Tours, France. 4. G5 Evolutionary Genomics of RNA Viruses, Institut Pasteur, Université Paris Cité, Paris, France. 5. Virus and Immunity Unit, Institut Pasteur, Université Paris Cité, CNRS UMR3569, Paris, France; École Doctorale BioSPC 562, Université de Paris, Paris, France. 6. Laboratoire de Virologie, Service de Microbiologie, Hôpital Européen Georges Pompidou, Paris, France. 7. Laboratoire de Virologie, Service de Microbiologie, Hôpital Européen Georges Pompidou, Paris, France; Functional Genomics of Solid Tumors (FunGeST), Centre de Recherche des Cordelier, INSERM, Université de Paris, Sorbonne Université, Paris, France. 8. Service de Maladies Infectieuses, CHR d'Orléans, Orléans, France. 9. Virus and Immunity Unit, Institut Pasteur, Université Paris Cité, CNRS UMR3569, Paris, France; Vaccine Research Institute, Créteil, France. 10. Virus and Immunity Unit, Institut Pasteur, Université Paris Cité, CNRS UMR3569, Paris, France; Vaccine Research Institute, Créteil, France. Electronic address: olivier.schwartz@pasteur.fr.
Abstract
BACKGROUND: Since early 2022, Omicron BA.1 has been eclipsed by BA.2, which was in turn outcompeted by BA.5, which displays enhanced antibody escape properties. METHODS: Here, we evaluated the duration of the neutralizing antibody (Nab) response, up to 18 months after Pfizer BNT162b2 vaccination, in individuals with or without BA.1/BA.2 breakthrough infection. We measured neutralization of the ancestral D614G lineage, Delta, and Omicron BA.1, BA.2, and BA.5 variants in 300 sera and 35 nasal swabs from 27 individuals. FINDINGS: Upon vaccination, serum Nab titers were decreased by 10-, 15-, and 25-fold for BA.1, BA.2, and BA.5, respectively, compared with D614G. We estimated that, after boosting, the duration of neutralization was markedly shortened from 11.5 months with D614G to 5.5 months with BA.5. After breakthrough, we observed a sharp increase of Nabs against Omicron subvariants, followed by a plateau and a slow decline after 5-6 months. In nasal swabs, infection, but not vaccination, triggered a strong immunoglobulin A (IgA) response and a detectable Omicron-neutralizing activity. CONCLUSIONS: BA.5 spread is partly due to abbreviated vaccine efficacy, particularly in individuals who were not infected with previous Omicron variants. FUNDING: Work in O.S.'s laboratory is funded by the Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale (FRM), ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2, ANR Coronamito, and IDISCOVR, Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant no. ANR-10-LABX-62-IBEID), HERA european funding and the NIH PICREID (grant no U01AI151758).
BACKGROUND: Since early 2022, Omicron BA.1 has been eclipsed by BA.2, which was in turn outcompeted by BA.5, which displays enhanced antibody escape properties. METHODS: Here, we evaluated the duration of the neutralizing antibody (Nab) response, up to 18 months after Pfizer BNT162b2 vaccination, in individuals with or without BA.1/BA.2 breakthrough infection. We measured neutralization of the ancestral D614G lineage, Delta, and Omicron BA.1, BA.2, and BA.5 variants in 300 sera and 35 nasal swabs from 27 individuals. FINDINGS: Upon vaccination, serum Nab titers were decreased by 10-, 15-, and 25-fold for BA.1, BA.2, and BA.5, respectively, compared with D614G. We estimated that, after boosting, the duration of neutralization was markedly shortened from 11.5 months with D614G to 5.5 months with BA.5. After breakthrough, we observed a sharp increase of Nabs against Omicron subvariants, followed by a plateau and a slow decline after 5-6 months. In nasal swabs, infection, but not vaccination, triggered a strong immunoglobulin A (IgA) response and a detectable Omicron-neutralizing activity. CONCLUSIONS: BA.5 spread is partly due to abbreviated vaccine efficacy, particularly in individuals who were not infected with previous Omicron variants. FUNDING: Work in O.S.'s laboratory is funded by the Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale (FRM), ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2, ANR Coronamito, and IDISCOVR, Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant no. ANR-10-LABX-62-IBEID), HERA european funding and the NIH PICREID (grant no U01AI151758).
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