IgA dominates the early neutralizing antibody response to SARS-CoV-2

被引:752
作者
Sterlin, Delphine [1 ,2 ,3 ]
Mathian, Alexis [1 ,4 ]
Miyara, Makoto [1 ,2 ]
Mohr, Audrey [1 ]
Anna, Francois [5 ,6 ]
Claer, Laetitia [1 ]
Quentric, Paul [1 ]
Fadlallah, Jehane [1 ,4 ]
Devilliers, Herve [7 ,8 ]
Ghillani, Pascale [2 ]
Gunn, Cary [9 ]
Hockett, Rick [9 ]
Mudumba, Sasi [9 ]
Guihot, Amelie [1 ,2 ]
Luyt, Charles-Edouard [10 ,11 ]
Mayaux, Julien [12 ]
Beurton, Alexandra [12 ,13 ]
Fourati, Salma [14 ,15 ]
Bruel, Timothee [16 ,17 ,18 ]
Schwartz, Olivier [16 ,17 ,18 ]
Lacorte, Jean-Marc [11 ,14 ]
Yssel, Hans [1 ]
Parizot, Christophe [1 ,2 ]
Dorgham, Karim [1 ]
Charneau, Pierre [5 ,6 ]
Amoura, Zahir [1 ,4 ]
Gorochov, Guy [1 ,2 ]
机构
[1] Sorbonne Univ, Ctr Immunol & Malad Infect CIMI Paris, INSERM, 91 Blvd Hop, F-75013 Paris, France
[2] Hop La Pitie Salpetriere, AP HP, Dept Immunol, 83 Blvd Hop, F-75013 Paris, France
[3] Inst Pasteur, Unit Antibodies Therapy & Pathol, INSERM, UMR1222, 25-28 Rue Dr Roux, F-75015 Paris, France
[4] Hop La Pitie Salpetriere, AP HP, Inst E3M, Serv Med Interne 2, 83 Blvd Hop, F-75013 Paris, France
[5] Inst Pasteur, Unite Virol Mol & Vaccinol, 25-28 Rue Dr Roux, F-75015 Paris, France
[6] Inst Pasteur, Theravectys, 25-28 Rue Dr Roux, F-75015 Paris, France
[7] CHU Dijon, Serv Med Interne & Malad Syst Med Interne 2, Hop Francois Mitterrand, 3 Rue FBG Raines, F-21000 Dijon, France
[8] Inserm CIC EC 1432, Ctr Invest Clin, 3 Rue FBG Raines, F-21000 Dijon, France
[9] Genalyte Inc, 10520 Wateridge Circle, San Diego, CA 92121 USA
[10] Sorbonne Univ, Inst Cardiol, Serv Med Intens Reanimat, Hop Pitie Salpetriere,AP HP, 83 Blvd lHop, F-75013 Paris, France
[11] Sorbonne Univ, UMRS 1166, INSERM, ICAN Inst Cardiometab & Nutr, 91 Blvd Hop, F-75013 Paris, France
[12] Hop La Pitie Salpetriere, AP HP, Serv Med Intens Reanimat & Pneumol, 83 Blvd Hop, F-75013 Paris, France
[13] Sorbonne Univ, AP HP, Inserm UMRS Neurophysiol Respiratoire Expt & Clin, 91 Blvd Hop, F-75013 Paris, France
[14] Hop La Pitie Salpetriere, AP HP, Serv Biochim Endocrinienne & Oncol, 83 Blvd Hop, F-75013 Paris, France
[15] Ctr Rech Inflammat Paris Montmartre CRI, Inserm, UMR1149, 16 Rue Henri Huchard, F-75890 Paris, France
[16] Inst Pasteur, Dept Virol, Virus & Immun Unit, 25-28 Rue Dr Roux, F-75015 Paris, France
[17] Inst Pasteur, CNRS, UMR3569, 25-28 Rue Dr Roux, F-75015 Paris, France
[18] Vaccine Res Inst, 51 Ave Marechal Lattre de Tassigny, F-94000 Creteil, France
关键词
HUMAN PLASMA-CELLS; INFLUENZA-VIRUS; INTRACELLULAR NEUTRALIZATION; CROSS-PROTECTION; HUMAN MUCOSAL; B-CELLS; SERUM; RECOMBINATION; EPIDEMIOLOGY; STRAINS;
D O I
10.1126/scitranslmed.abd2223
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Humoral immune responses are typically characterized by primary IgM antibody responses followed by secondary antibody responses associated with immune memory and composed of IgG, IgA, and IgE. Here, we measured acute humoral responses to SARS-CoV-2, including the frequency of antibody-secreting cells and the presence of SARS-CoV-2-specific neutralizing antibodies in the serum, saliva, and bronchoalveolar fluid of 159 patients with COVID-19. Early SARS-CoV-2-specific humoral responses were dominated by IgA antibodies. Peripheral expansion of IgA plasmablasts with mucosal homing potential was detected shortly after the onset of symptoms and peaked during the third week of the disease. The virus-specific antibody responses included IgG, IgM, and IgA, but IgA contributed to virus neutralization to a greater extent compared with IgG. Specific IgA serum concentrations decreased notably 1 month after the onset of symptoms, but neutralizing IgA remained detectable in saliva for a longer time (days 49 to 73 post-symptoms). These results represent a critical observation given the emerging information as to the types of antibodies associated with optimal protection against reinfection and whether vaccine regimens should consider targeting a potent but potentially short-lived IgA response.
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页数:10
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