The GFP area and the number of nuclei were quantified using the Harmony software (PerkinElmer)

The GFP area and the number of nuclei were quantified using the Harmony software (PerkinElmer). neutralization was markedly shortened from 11.5 Alas2 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 sluggish decrease after 56 weeks. In nose swabs, infection, but not vaccination, induced 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 from the Institut Pasteur, Urgence COVID-19 Fundraising Marketing campaign of Institut Pasteur, Fondation pour la Recherche Mdicale (FRM), ANRS, the Vaccine Study Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Adobe flash Covid PROTEO-SARS-CoV-2, ANR Coronamito, and IDISCOVR, Laboratoire dExcellence Integrative Biology of Emerging Infectious Diseases (give no. ANR-10-LABX-62-IBEID), HERA western funding and the NIH PICREID (give no U01AI151758). Keywords:SARS-Cov-2, variants, Omicron, BA.5, neutralization, vaccine, breakthrough, mucosal immunity, IgG, IgA == Graphical abstract == == Context and significance == Since the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant in December 2022, approximately 50% of the world human population has been infected, reflecting a poor protection against illness conferred by vaccination. Experts from Paris, France, statement that, upon vaccination, the period of an efficient antibody response was significantly shorter for Omicron variants, including BA.5, compared with the ancestral strain. After breakthrough infection, antibody Ro 31-8220 mesylate levels against Omicron subvariants improved, and remained elevated for at least 56 weeks. Breakthrough infection, but not vaccination, induced detectable local response in Ro 31-8220 mesylate the nose mucosa against SARS-CoV-2. These results show the longitudinal survey of antibody levels Ro 31-8220 mesylate in blood and nose samples may provide a reliable marker of the effectiveness of vaccination, natural, and cross immunity against acquisition of current and future SARS-CoV-2 variants. Planas et al. analyze the degree and duration of the neutralizing antibody response after vaccination with Pfizer BNT162b2 mRNA in the sera and nose swabs from individuals with or without Omicron breakthrough infection, finding a short period of Ro 31-8220 mesylate neutralization against BA.5 after boosting and strong immunoglobulin A (IgA) response upon breakthrough infection. == Intro == The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.1 and BA.2 variants spread across the world and replaced the Delta variant in early 2022.1It is estimated that more than 50% of the population were infected by BA.1 or BA.2 by March 20222with little protection against illness conferred by vaccination.3,4,5The incidence of breakthrough infections in vaccinated individuals has thus dramatically increased since Omicron emerged.6BA.1 and BA.2 contain approximately 32 changes in the spike protein, promoting their high transmissibility and immune escape properties.7,8,9,10,11,12,13,14,15,16,17The Omicron clade has rapidly evolved into sub-lineages, including BA.5, that outcompeted BA.1 and BA.2.18The BA.5 spike shares multiple changes noted in BA.2 and bears a few additional modifications. BA.5 became predominant worldwide by mid-2022 and was responsible for a surge of infections in many countries.18,19The neutralizing activity of sera from COVID-19 vaccine recipients is reduced against BA.5 by approximately three- to five-fold compared with BA.1 and BA.2.11,20,21,22,23,24Here, we assessed the durability and magnitude of neutralizing antibody (Nab) responses against different Omicron variants, up to 18 months after Pfizer BNT162b2 vaccination. We also analyzed the development of Nabs in the sera and nose swabs from vaccine recipients who experienced BA.1 or BA.2 breakthrough infections. We statement a shortened duration of neutralization against BA.5 Nabs in the sera of vaccine recipients, and a presence of such antibodies in nasal swabs only after breakthrough infection. == Results == == Cohort design == We longitudinally collected 300 sera and 35 nose samples from a cohort of 27 health care workers in Orleans, France. We previously analyzed the ability of some of these sera to neutralize the Alpha, Beta, Delta, and Omicron BA.1 variants.10The characteristics of each participant are indicated inTable S1. The participants, who were not previously infected at the time of inclusion, received two doses of Pfizer BNT162b2 vaccine within an interval of 2128 days and a booster dose 154361 days later on. Of the 27 individuals, 11 experienced a pauci-symptomatic breakthrough.