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2.
Front Immunol ; 13: 790334, 2022.
Article in English | MEDLINE | ID: covidwho-1715001

ABSTRACT

The capacity of pre-existing immunity to human common coronaviruses (HCoV) to cross-protect against de novo COVID-19is yet unknown. In this work, we studied the sera of 175 COVID-19 patients, 76 healthy donors and 3 intravenous immunoglobulins (IVIG) batches. We found that most COVID-19 patients developed anti-SARS-CoV-2 IgG antibodies before IgM. Moreover, the capacity of their IgGs to react to beta-HCoV, was present in the early sera of most patients before the appearance of anti-SARS-CoV-2 IgG. This implied that a recall-type antibody response was generated. In comparison, the patients that mounted an anti-SARS-COV2 IgM response, prior to IgG responses had lower titres of anti-beta-HCoV IgG antibodies. This indicated that pre-existing immunity to beta-HCoV was conducive to the generation of memory type responses to SARS-COV-2. Finally, we also found that pre-COVID-19-era sera and IVIG cross-reacted with SARS-CoV-2 antigens without neutralising SARS-CoV-2 infectivity in vitro. Put together, these results indicate that whilst pre-existing immunity to HCoV is responsible for recall-type IgG responses to SARS-CoV-2, it does not lead to cross-protection against COVID-19.


Subject(s)
Betacoronavirus/physiology , COVID-19/immunology , Common Cold/immunology , Immunoglobulins, Intravenous/therapeutic use , SARS-CoV-2/physiology , Aged , Aged, 80 and over , Antibodies, Neutralizing/metabolism , Antibodies, Viral/metabolism , Antigens, Viral/immunology , COVID-19/mortality , COVID-19/therapy , Cross Reactions , Female , Humans , Immunity, Heterologous , Immunoglobulin G/metabolism , Immunoglobulin M/metabolism , Immunologic Memory , Male , Middle Aged , Survival Analysis
4.
Ann Rheum Dis ; 81(4): 575-583, 2022 04.
Article in English | MEDLINE | ID: covidwho-1450597

ABSTRACT

OBJECTIVES: Our aim was to evaluate systemic lupus erythematosus (SLE) disease activity and SARS-CoV-2-specific immune responses after BNT162b2 vaccination. METHODS: In this prospective study, disease activity and clinical assessments were recorded from the first dose of vaccine until day 15 after the second dose in 126 patients with SLE. SARS-CoV-2 antibody responses were measured against wild-type spike antigen, while serum-neutralising activity was assessed against the SARS-CoV-2 historical strain and variants of concerns (VOCs). Vaccine-specific T cell responses were quantified by interferon-γ release assay after the second dose. RESULTS: BNT162b2 was well tolerated and no statistically significant variations of BILAG (British Isles Lupus Assessment Group) and SLEDAI (SLE Disease Activity Index) scores were observed throughout the study in patients with SLE with active and inactive disease at baseline. Mycophenolate mofetil (MMF) and methotrexate (MTX) treatments were associated with drastically reduced BNT162b2 antibody response (ß=-78, p=0.007; ß=-122, p<0.001, respectively). Anti-spike antibody response was positively associated with baseline total immunoglobulin G serum levels, naïve B cell frequencies (ß=2, p=0.018; ß=2.5, p=0.003) and SARS-CoV-2-specific T cell response (r=0.462, p=0.003). In responders, serum neutralisation activity decreased against VOCs bearing the E484K mutation but remained detectable in a majority of patients. CONCLUSION: MMF, MTX and poor baseline humoral immune status, particularly low naïve B cell frequencies, are independently associated with impaired BNT162b2 mRNA antibody response, delineating patients with SLE who might need adapted vaccine regimens and follow-up.


Subject(s)
Antirheumatic Agents/adverse effects , Immunity, Humoral/drug effects , Lupus Erythematosus, Systemic/immunology , SARS-CoV-2/immunology , Adult , Antibodies, Viral/immunology , Antirheumatic Agents/immunology , COVID-19/prevention & control , Female , Humans , Immunogenicity, Vaccine/drug effects , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/virology , Male , Methotrexate/adverse effects , Methotrexate/immunology , Middle Aged , Mycophenolic Acid/adverse effects , Mycophenolic Acid/immunology , Prospective Studies , Severity of Illness Index
6.
Nat Commun ; 12(1): 844, 2021 02 08.
Article in English | MEDLINE | ID: covidwho-1069105

ABSTRACT

There are only few data concerning persistence of neutralizing antibodies (NAbs) among SARS-CoV-2-infected healthcare workers (HCW). These individuals are particularly exposed to SARS-CoV-2 infection and at potential risk of reinfection. We followed 26 HCW with mild COVID-19 three weeks (D21), two months (M2) and three months (M3) after the onset of symptoms. All the HCW had anti-receptor binding domain (RBD) IgA at D21, decreasing to 38.5% at M3 (p < 0.0001). Concomitantly a significant decrease in NAb titers was observed between D21 and M2 (p = 0.03) and between D21 and M3 (p < 0.0001). Here, we report that SARS-CoV-2 can elicit a NAb response correlated with anti-RBD antibody levels. However, this neutralizing activity declines, and may even be lost, in association with a decrease in systemic IgA antibody levels, from two months after disease onset. This short-lasting humoral protection supports strong recommendations to maintain infection prevention and control measures in HCW, and suggests that periodic boosts of SARS-CoV-2 vaccination may be required.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Health Personnel/statistics & numerical data , SARS-CoV-2/immunology , Adult , Binding Sites/immunology , COVID-19/virology , Cell Line, Tumor , Female , Humans , Immunoglobulin A/immunology , Male , Middle Aged , Protein Binding , Receptors, Virus/metabolism , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Time Factors
7.
Pharmacology ; 106(1-2): 9-19, 2021.
Article in English | MEDLINE | ID: covidwho-1066969

ABSTRACT

BACKGROUND: Extensive efforts have been made in optimizing monoclonal immunoglobulin (Ig)G antibodies for use in clinical practice. Accumulating evidence suggests that IgA or anti-FcαRI could also represent an exciting avenue toward novel therapeutic strategies. SUMMARY: Here, we underline that IgA is more effective in recruiting neutrophils for tumor cell killing and is potently active against several pathogens, including rotavirus, poliovirus, influenza virus, and SARS-CoV-2. IgA could also be used to modulate excessive immune responses in inflammatory diseases. Furthermore, secretory IgA is emerging as a major regulator of gut microbiota, which impacts intestinal homeostasis and global health as well. As such, IgA could be used to promote a healthy microbiota in a therapeutic setting. Key messages: IgA combines multifaceted functions that can be desirable for immunotherapy.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Immunoglobulin A/therapeutic use , Immunotherapy , SARS-CoV-2/immunology , Animals , Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal/adverse effects , Antineoplastic Agents, Immunological/therapeutic use , Antiviral Agents/adverse effects , COVID-19/immunology , COVID-19/virology , Host-Pathogen Interactions , Humans , Immunoglobulin A/adverse effects , Immunotherapy/adverse effects , Inflammation/drug therapy , Inflammation/immunology , Mice , Neoplasms/drug therapy , Neoplasms/immunology
8.
Sci Transl Med ; 13(577)2021 01 20.
Article in English | MEDLINE | ID: covidwho-963895

ABSTRACT

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.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/diagnosis , Immunity, Humoral , Immunoglobulin A/blood , SARS-CoV-2/immunology , Biomarkers/blood , Bronchoalveolar Lavage Fluid/immunology , Bronchoalveolar Lavage Fluid/virology , COVID-19/blood , COVID-19/immunology , COVID-19/virology , Case-Control Studies , Host-Pathogen Interactions , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Longitudinal Studies , Saliva/immunology , Saliva/virology , Time Factors
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