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1. Antibody and T cell memory immune response after two doses of the BNT162b2 mRNA vaccine in older adults with and without prior SARS-CoV-2 infection

Author

K. Faure, Annie Sobaszek, F. Vuotto, Enagnon Kazali Alidjinou, B. Corroyer-Simovic, J. Podvin, Dominique Huvent-Grelle, Alain Duhamel, Anne Goffard, Julien Labreuche, Dominique Deplanque, Arnaud Dendooven, Miczek S, François Puisieux, Guillaume Lefèvre, Julie Demaret, Myriam Labalette, Laurence Bocket, Jacques Trauet, and Daniel Dreuil

Subjects
biology, business.industry, T cell, Antibody titer, Titer, medicine.anatomical_structure, Immune system, Immunology, biology.protein, Medicine, Young adult, Antibody, business, Neutralizing antibody, CD8
Abstract

We quantified S1-specific IgG, neutralizing antibody titers, specific IFNγ secreting T cells and functionality of specific CD4+ and CD8+ T cells in 130 young adults (median age 44.0 years) and 106 older residents living in a long-term care facility (86.5 years) after 2 doses of BNT162b2. Three months after the first injection, humoral and cellular memory responses were dramatically impaired in the 54 COVID-19-naive older compared to the 121 COVID-19-naive younger adults. Notably, older participants’ neutralizing antibodies, detected in 76.5% (versus 100% in young adults,P< 0.0001), were ten times lower than the younger’s antibody titers (P< 0.0001). Antibody and T cell responses were greater among the 52 COVID-19-recovered than among the 54 COVID-19-naive older adults (P< 0.0001). Our study shows that 2 doses of BNT162b2 does not guarantee long-term protection against SARS-CoV-2 in the older. An additional dose should be considered to boost their specific memory response.

Published
2021
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2. 'Women in the middle': An observational study of a generation story in Alzheimer disease in France

Author

Dominique Huvent-Grelle, François Puisieux, J. Podvin, Eric Boulanger, T. Martin, and Jean-Baptiste Beuscart

Subjects
Gerontology, business.industry, Mean age, Grandparent, Disease, Caregiver burden, medicine.disease, Distress, Quality of life (healthcare), medicine, Observational study, Geriatrics and Gerontology, Alzheimer's disease, business
Abstract

Background It is well known that informal care giving for Alzheimer patients can be a burden and may result in caregivers’ distress and stress. Caring for a person with Alzheimer's disease (AD) is a difficult task, which can become overwhelming. Their caregivers need attention as well. Objectives The present study examines the socio-demographic characteristics and the quality of health and life of the sandwich grandparent generation (SGP) caregivers defined as providing care to both old demented parents and young grandchildren. Study design Multicentric, prospective and observational study over a one-year period. Setting Eleven voluntary Memory Clinics across the North of France. Participants Voluntary SGP caregivers recruited in Memory Clinics who completed an oral questionnaire, during an interview one to one with a physician. Results A vast majority of our SGP caregivers were women, mean age 59 years, married, retired, described in the literature as “women in the middle”, felling stressed and not sleeping well in more than half of the cases. They had three grandchildren, mean age 7 years. The AD patient, mean age 86-years-old, was most frequently the caregiver's mother. Many SGPs had been providing their help for 5 years or even longer. Nevertheless, the SGPs considered themselves satisfied about their health, and said they had a good quality of life. Conclusion Although SGP women caregivers reported high levels of perceived burden, they considered that their health and quality of life were good.

Published
2015
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3. Overview of the Chemistry-Aerosol Mediterranean Experiment/Aerosol Direct Radiative Forcing on the Mediterranean Climate (ChArMEx/ADRIMED) summer 2013 campaign

Author

M. Mallet, F. Dulac, P. Formenti, P. Nabat, J. Sciare, G. Roberts, J. Pelon, G. Ancellet, D. Tanré, F. Parol, A. di Sarra, L. Alados, J. Arndt, F. Auriol, L. Blarel, T. Bourrianne, G. Brogniez, P. Chazette, S. Chevaillier, M. Claeys, B. D'Anna, C. Denjean, Y. Derimian, K. Desboeufs, T. Di Iorio, J.-F. Doussin, P. Durand, A. Féron, E. Freney, C. Gaimoz, P. Goloub, J. L. Gómez-Amo, M. J. Granados-Muñoz, N. Grand, E. Hamonou, I. Jankowiak, M. Jeannot, J.-F. Léon, M. Maillé, S. Mailler, D. Meloni, L. Menut, G. Momboisse, J. Nicolas, J. Podvin, V. Pont, G. Rea, J.-B. Renard, L. Roblou, K. Schepanski, A. Schwarzenboeck, K. Sellegri, M. Sicard, F. Solmon, S. Somot, B. Torres, J. Totems, S. Triquet, N. Verdier, C. Verwaerde, J. Wenger, P. Zapf, Laboratoire d'aérologie (LA), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Université Fédérale Toulouse Midi-Pyrénées-Centre National d'Études Spatiales [Toulouse] (CNES)-Météo France-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Météo France-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA (UMR_7583)), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Groupe d'étude de l'atmosphère météorologique (CNRM-GAME), Institut national des sciences de l'Univers (INSU - CNRS)-Météo France-Centre National de la Recherche Scientifique (CNRS), Energy, Environment and Water Research Center (EEWRC), Cyprus Institute (CyI), TROPO - LATMOS, Laboratoire Atmosphères, Milieux, Observations Spatiales (LATMOS), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Laboratoire d’Optique Atmosphérique - UMR 8518 (LOA), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Laboratory for Earth Observations and Analyses, Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), Departamento de Fisica Aplicada [Granada], Universidad de Granada (UGR), Department of Chemistry [Cork], University College Cork (UCC), Environmental Research Institute [Cork] (ERI), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Leibniz Institute for Tropospheric Research (TROPOS), Dipartimento di Fisica [Roma La Sapienza], Università degli Studi di Roma 'La Sapienza' [Rome], Laboratoire de météorologie physique (LaMP), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Laboratoire de Physique et Chimie de l'Environnement et de l'Espace (LPC2E), Observatoire des Sciences de l'Univers en région Centre (OSUC), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)-Centre National d’Études Spatiales [Paris] (CNES), Laboratoire de Météorologie Dynamique (UMR 8539) (LMD), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-École des Ponts ParisTech (ENPC)-Centre National de la Recherche Scientifique (CNRS)-Département des Géosciences - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Universitat Politècnica de Catalunya [Barcelona] (UPC), Abdus Salam International Centre for Theoretical Physics [Trieste] (ICTP), Centre National d'Études Spatiales [Toulouse] (CNES), Agence Nationale de la Recherche (ANR), ADEME, CEA, CNRS-INSU, Météo-France, Collectivité Territoriale de Corse, CNES, Italian Ministry for University and Research, 7th Framework Programme under the project ACTRIS, ANR-11-BS56-0006,ADRIMED,Impact du forçage radiatif direct des aérosols sur le climat Méditerranéen.(2011), Centre National de la Recherche Scientifique (CNRS)-Observatoire Midi-Pyrénées (OMP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut national des sciences de l'Univers (INSU - CNRS), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO)-Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO)-Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Centre National d’Études Spatiales [Paris] (CNES), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Université Fédérale Toulouse Midi-Pyrénées-Centre National d'Études Spatiales [Toulouse] (CNES)-Météo France-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Université Fédérale Toulouse Midi-Pyrénées-Centre National d'Études Spatiales [Toulouse] (CNES)-Météo France-Université Toulouse III - Paul Sabatier (UT3), Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'aérologie (LAERO), Université de Toulouse (UT)-Université de Toulouse (UT)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre national de recherches météorologiques (CNRM), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Agenzia Nazionale per le nuove Tecnologie, l’energia e lo sviluppo economico sostenibile = Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), Universidad de Granada = University of Granada (UGR), Cyprus International Institute for the Environment and Public Health, Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Météorologie Physique (LaMP), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-École des Ponts ParisTech (ENPC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département des Géosciences - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), European Project: 262254,EC:FP7:INFRA,FP7-INFRASTRUCTURES-2010-1,ACTRIS(2011), European Project: 654109,H2020,H2020-INFRAIA-2014-2015,ACTRIS-2(2015), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), and University of Granada [Granada]

Subjects
[PHYS.PHYS.PHYS-AO-PH]Physics [physics]/Physics [physics]/Atmospheric and Oceanic Physics [physics.ao-ph], 010504 meteorology & atmospheric sciences, 13. Climate action, [SDU.STU.CL]Sciences of the Universe [physics]/Earth Sciences/Climatology, [SDU]Sciences of the Universe [physics], 14. Life underwater, 010502 geochemistry & geophysics, 01 natural sciences, 0105 earth and related environmental sciences
Abstract

International audience The Chemistry-Aerosol Mediterranean Experiment (ChArMEx; http://charmex.lsce.ipsl.fr) is a collaborative research program federating international activities to investigate Mediterranean regional chemistry-climate interactions. A special observing period (SOP-1a) including intensive airborne measurements was performed in the framework of the Aerosol Direct Radiative Forcing on the Mediterranean Climate (ADRIMED) project during the Mediterranean dry season over the western and central Mediterranean basins, with a focus on aerosol-radiation measurements and their modeling. The SOP-1a took place from 11 June to 5 July 2013. Airborne measurements were made by both the ATR-42 and F-20 French research aircraft operated from Sardinia (Italy) and instrumented for in situ and remote-sensing measurements, respectively, and by sounding and drifting balloons, launched in Minorca. The experimental set-up also involved several ground-based measurement sites on islands including two ground-based reference stations in Corsica and Lampedusa and secondary monitoring sites in Minorca and Sicily. Additional measurements including lidar profiling were also performed on alert during aircraft operations at EARLINET/ACTRIS stations at Granada and Barcelona in Spain, and in southern Italy. Remote sensing aerosol products from satellites (MSG/SEVIRI, MODIS) and from the AERONET/PHOTONS network were also used. Dedicated meso-scale and regional modelling experiments were performed in relation to this observational effort. We provide here an overview of the different surface and aircraft observations deployed during the ChArMEx/ADRIMED period and of associated modeling studies together with an analysis of the synoptic conditions that determined the aerosol emission and transport. Meteorological conditions observed during this campaign (moderate temperatures and southern flows) were not favorable to produce high level of atmospheric pollutants nor intense biomass burning events in the region. However, numerous mineral dust plumes were observed during the campaign with main sources located in Morocco, Algeria and Tunisia, leading to aerosol optical depth (AOD) values ranging between 0.2 to 0.6 (at 440 nm) over the western and central Mediterranean basins. Associated aerosol extinction values measured on-board the ATR-42 within the dust plume show local maxima reaching up to 150 Mm$^{-1}$. Non negligible aerosol extinction (about 50 Mm$^{-1}$) was also been observed within the Marine Boundary Layer (MBL). By combining ATR-42 extinction, absorption and scattering measurements, a complete optical closure has been made revealing excellent agreement with estimated optical properties. Associated calculations of the dust single scattering albedo (SSA) have been conducted, which show a moderate variability (from 0.90 to 1.00 at 530 nm). In parallel, active remote-sensing observations from the surface and onboard the F-20 aircraft suggest a complex vertical structure of particles and distinct aerosol layers with sea-salt and pollution located within the MBL, and mineral dust and/or aged north American smoke particles located above (up to 6-7 km in altitude). Aircraft and balloon-borne observations show particle size distributions characterized by large aerosols (> 10 μm in diameter) within dust plumes. In terms of shortwave (SW) direct forcing, in-situ surface and aircraft observations have been merged and used as inputs in 1-D radiative transfer codes for calculating the direct radiative forcing (DRF). Results show significant surface SW instantaneous forcing (up to -90 W m$^{-2}$ at noon). Associated 3-D modeling studies from regional climate (RCM) and chemistry transport (CTM) models indicate a relatively good agreement for simulated AOD compared with measurements/observations from the AERONET/PHOTONS network and satellite data, especially for long-range dust transport. Calculations of the 3-D SW (clear-sky) surface DRF indicate an average of about -10 to -20 W m$^{-2}$ (for the whole period) over the Mediterranean Sea together with maxima (-50 W m$^{-2}$) over northern Africa. The top of the atmosphere (TOA) DRF is shown to be highly variable within the domain, due to moderate absorbing properties of dust and changes in the surface albedo. Indeed, 3-D simulations indicate negative forcing over the Mediterranean Sea and Europe and positive forcing over northern Africa.

Published
2015
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4. Serum neutralization of SARS coronavirus 2 Omicron sublineages BA.1 and BA.2 and cellular immune responses 3 months after booster vaccination.

Author

Alidjinou EK, Demaret J, Corroyer-Simovic B, Vuotto F, Miczek S, Labreuche J, Goffard A, Trauet J, Lupau D, Dendooven A, Huvent-Grelle D, Podvin J, Dreuil D, Faure K, Deplanque D, Bocket L, Duhamel A, Sobaszek A, Hober D, Hisbergues M, Puisieux F, Autran B, Yazdanpanah Y, Labalette M, and Lefèvre G

Subjects
Humans, BNT162 Vaccine, Antibodies, Neutralizing, Immunity, Cellular, Vaccination, Antibodies, Viral, SARS-CoV-2, COVID-19 prevention & control
Abstract

Objectives: We investigated serum neutralizing activity against BA.1 and BA.2 Omicron sublineages and T cell response before and 3 months after administration of the booster vaccine in healthcare workers (HCWs)., Methods: HCWs aged 18-65 years who were vaccinated and received booster doses of the BNT162b2 vaccine were included. Anti-SARS coronavirus 2 IgG levels and cellular response (through interferon γ ELISpot assay) were evaluated in all participants, and neutralizing antibodies against Delta, BA.1, and BA.2 were evaluated in participants with at least one follow-up visit 1 or 3 months after the administration of the booster dose., Results: Among 118 HCWs who received the booster dose, 102 and 84 participants attended the 1-month and 3-month visits, respectively. Before the booster vaccine dose, a low serum neutralizing activity against Delta, BA.1, and BA.2 was detectable in only 39/102 (38.2%), 8/102 (7.8%), and 12/102 (11.8%) participants, respectively. At 3 months, neutralizing antibodies against Delta, BA.1, and BA.2 were detected in 84/84 (100%), 79/84 (94%), and 77/84 (92%) participants, respectively. Geometric mean titres of neutralizing antibodies against BA.1 and BA.2 were 2.2-fold and 2.8-fold reduced compared with those for Delta. From 1 to 3 months after the administration of the booster dose, participants with a recent history of SARS coronavirus 2 infection (n = 21/84) had persistent levels of S1 reactive specific T cells and neutralizing antibodies against Delta and BA.2 and 2.2-fold increase in neutralizing antibodies against BA.1 (p 0.014). Conversely, neutralizing antibody titres against Delta (2.5-fold decrease, p < 0.0001), BA.1 (1.5-fold, p 0.02), and BA.2 (2-fold, p < 0.0001) declined from 1 to 3 months after the administration of the booster dose in individuals without any recent infection., Discussion: The booster vaccine dose provided significant and similar response against BA.1 and BA.2 Omicron sublineages; however, the immune response declined in the absence of recent infection., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Published
2023
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5. Immunogenicity of BNT162b2 vaccine booster against SARS-CoV-2 Delta and Omicron variants in nursing home residents: A prospective observational study in older adults aged from 68 to 98 years.

Author

Alidjinou EK, Demaret J, Corroyer-Simovic B, Labreuche J, Goffard A, Trauet J, Lupau D, Miczek S, Vuotto F, Dendooven A, Huvent-Grelle D, Podvin J, Dreuil D, Faure K, Deplanque D, Bocket L, Duhamel A, Sobaszek A, Hober D, Hisbergues M, Puisieux F, Autran B, Yazdanpanah Y, Labalette M, and Lefèvre G

Abstract

Background: The present study aimed to evaluate the persistent immunogenicity offered by a third dose of BNT162b2 against Delta and Omicron variants, in nursing home (NH) residents., Methods: In this monocenter prospective observational study, anti-spike IgG levels, S1 domain reactive T cell counts, serum neutralizing antibody titers against Delta and Omicron variants were compared before and up to three months after the BNT162b2 booster dose, in NH residents without COVID-19 (COVID-19 naive) or with COVID-19 prior to initial vaccination (COVID-19 recovered)., Findings: 106 NH residents (median [interquartile range] age: 86·5 [81;91] years) were included. The booster dose induced a high increase of anti-spike antibody levels in all subjects ( p  < 0.0001) and a mild transient increase of specific T cells. Before the booster dose, Delta neutralization was detected in 19% ( n  = 8/43) and 88% ( n  = 37/42) of COVID-19 naive and COVID-19 recovered subjects, respectively. Three months after the booster dose, all NH residents developed and maintained a higher Delta neutralization ( p  < 0·0001). Before the booster dose, Omicron neutralization was detected in 5% ( n  = 2/43) and 55% ( n  = 23/42) of COVID-19 naive and COVID-19 recovered subjects, respectively, and three months after, in 84% and 95%, respectively. Neutralizing titers to Omicron were lower than to Delta in both groups with a 35-fold reduction compared to Delta., Interpretation: The booster dose restores high neutralization titers against Delta in all NH residents, and at a lower level against Omicron in a large majority of participants. Future studies are warranted to assess if repeated BNT162b2 booster doses or new specific vaccines might be considered for protecting such fragile patients against Omicron and/or future SARS-CoV-2 variants., Funding: French government through the Programme Investissement d'Avenir (I-SITE ULNE/ANR-16-IDEX-0004 ULNE) and the Label of COVID-19 National Research Priority (National Steering Committee on Therapeutic Trials and Other COVID-19 Research, CAPNET)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 The Authors.)

Published
2022
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6. Impaired Functional T-Cell Response to SARS-CoV-2 After Two Doses of BNT162b2 mRNA Vaccine in Older People.

Author

Demaret J, Corroyer-Simovic B, Alidjinou EK, Goffard A, Trauet J, Miczek S, Vuotto F, Dendooven A, Huvent-Grelle D, Podvin J, Dreuil D, Faure K, Deplanque D, Bocket L, Duhamel A, Labreuche J, Sobaszek A, Hisbergues M, Puisieux F, Labalette M, and Lefèvre G

Subjects
Adult, Aged, 80 and over, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, COVID-19 prevention & control, Female, Frailty immunology, Humans, Immunogenicity, Vaccine, Immunosenescence immunology, Male, Middle Aged, Nutritional Status immunology, BNT162 Vaccine immunology, COVID-19 immunology, SARS-CoV-2 immunology, T-Lymphocytes immunology
Abstract

Long-term care facility (LTCF) older residents display physiological alterations of cellular and humoral immunity that affect vaccine responses. Preliminary reports suggested a low early postvaccination antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to focus on the specific T-cell response. We quantified S1-specific IgG, neutralizing antibody titers, total specific IFNγ-secreting T cells by ELISpot, and functionality of CD4 + - and CD8 + -specific T cells by flow cytometry, after two doses of the BNT162b2 vaccine in younger and older people, with and without previous COVID-19 infection (hereafter referred to as COVID-19-recovered and COVID-19-naive subjects, respectively). Frailty, nutritional, and immunosenescence parameters were collected at baseline in COVID-19-naive older people. We analyzed the immune response in 129 young adults (median age 44.0 years) and 105 older residents living in a LCTF (median age 86.5 years), 3 months after the first injection. Humoral and cellular memory responses were dramatically impaired in the COVID-19-naive older ( n  = 54) compared with the COVID-19-naive younger adults ( n  = 121). Notably, older participants' neutralizing antibodies were 10 times lower than the younger's antibody titers ( p  < 0.0001) and LCTF residents also had an impaired functional T-cell response: the frequencies of IFNγ + and IFNγ + IL-2 + TNFα + cells among specific CD4 + T cells, and the frequency of specific CD8 + T cells were lower in COVID-19-naive older participants than in COVID-19-naive young adults ( p  < 0.0001 and p  = 0.0018, respectively). However, COVID-19-recovered older participants ( n  = 51) had greater antibody and T-cell responses, including IFNγ + and IFNγ + IL-2 + TNFα + -specific CD4 + T cells ( p  < 0.0001), as well as TNFα + -specific CD8 + T cells ( p  < 0.001), than COVID-19-naive older adults. We also observed that "inflammageing" and particularly high plasma levels of TNFα was associated to poor antibody response in the older participants. In conclusion, our results show that the COVID-19-naive older people had low counts and impaired specific CD4 + and CD8 + T cells, in addition to impaired antibody response, and that specific studies are warranted to assess the efficiency of SARS-CoV-2 mRNA-based vaccines, as in other immunocompromised subjects. Our study also shows that, despite their physiological alterations of immunity, vaccination is highly efficient in boosting the prior natural memory response in COVID-19-recovered older people., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Demaret, Corroyer-Simovic, Alidjinou, Goffard, Trauet, Miczek, Vuotto, Dendooven, Huvent-Grelle, Podvin, Dreuil, Faure, Deplanque, Bocket, Duhamel, Labreuche, Sobaszek, Hisbergues, Puisieux, Labalette and Lefèvre.)

Published
2021
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