Cellular and Humoral Immune Responses and Breakthrough Infections After Two Doses of BNT162b Vaccine in Healthcare Workers (HW) 180 Days After the Second Vaccine Dose

Frontiers in Public Health

article

Alessandra Mangia¹  Nicola Serra²  Giovanna Cocomazzi¹  Vincenzo Giambra³  Stefano Antinucci⁴  Alberto Maiorana⁵  Francesco Giuliani⁶  Emanuele Montomoli⁷  Paolo Cantaloni⁸  Alessandro Manenti⁸  Valeria Piazzolla¹ 

[1] Liver Unit;Department of Public Health, University “Federico II”;Institute for Stem Cell Biology, Regenerative Medicine and Innovative Therapies;Allergy Diagnostic Section Euroimmun;GSSL Unit;ICT Innovation and Research Unit;Department of Molecular and Developmental Medicine, University of Siena;VisMederi Srl

关键词: SARS-CoV-2;    mRNA vaccines;    humoral response;    IFN-γ;    healthcare workers;   

DOI  :  10.3389/fpubh.2022.847384

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Background Immunity and clinical protection induced by mRNA vaccines against SARS-CoV-2 have been shown to decline overtime. To gather information on the immunity profile deemed sufficient in protecting against hospitalization, we tested IgG levels, interferon-gamma (IFN-γ) secretion, and neutralizing antibodies 180 days (d180) after the second shot of BNT162b vaccine, in HW. Methods A total of 392 subjects were enrolled. All received BioNTech/Pfizer from February 2020 to April 2021. The vaccine-specific humoral response was quantitatively determined by testing for IgG anti-S1 domain of SARS-CoV-spike protein. Live virus microneutralization (MN) was evaluated by an assay performing incubation of serial 2-fold dilution of human serum samples, starting from 1:10 to 1:5120, with an equal volume of Wuhan strain and Delta VOC viral solution and assessing the presence/absence of a cytopathic effect. SARS-CoV-2-spike protein-specific T-cell response was determined by a commercial IFN-γ release assay. Results In 352 individuals, at d180, IgG levels decreased substantially but no results below the assay's positivity threshold were observed. Overall, 22 naive (8.1%) had values above the highest threshold. Among COVID-naive, the impact of age, which was observed at earlier stages, disappeared at d180, while it remained significant for 81 who had experienced a previous infection. Following the predictive model of protection by Khoury, we transformed the neutralizing titers in IU/ml and used a 54 IU/ml threshold to identify subjects with 50% protective immunity. Overall, live virus MN showed almost all subjects with previous exposure to SARS-CoV-2 neutralized the virus as compared to 33% of naive double-dosed subjects ( p 200 mIU/ml); among 271 naive, 7 (2.58%) and 17 (6.27%) subjects did not show borderline or strong secretion, respectively. Conclusions In naive subjects, low IgG titers are relatively long-lasting. Only a third of naive subjects maintain neutralizing responses. After specific stimulation, a very limited number of naive were unable to produce IFN-γ. The results attained in the small group of subjects with breakthrough infection suggest that simultaneous neutralizing antibody titers <20, binding antibody levels/ml <200, and IFN-γ <1,000 mIU/ml in subjects older than 58 may identify at-risk groups.

【 授权许可】

CC BY