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1.
Lancet Infect Dis ; 22(2): e52-e58, 2022 02.
Article in English | MEDLINE | ID: covidwho-1751515

ABSTRACT

As the number of individuals vaccinated against SARS-CoV-2 rises worldwide, population-level data regarding the vaccines' ability to reduce infection are being generated. Randomised trials have shown that these vaccines dramatically reduce symptomatic COVID-19; however, less is known about their effects on transmission between individuals. The natural course of infection with SARS-CoV-2 involves infection of the respiratory epithelia and replication within the mucosa to sufficient viral titres for transmission via aerosol particles and droplets. Here we discuss the available data on the existing, approved SARS-CoV-2 vaccines' capacity to reduce transmissibility by reducing primary infection, viral replication, capacity for transmission, and symptomaticity. The potential for mucosal-targeted SARS-CoV-2 vaccine strategies to more effectively limit transmission than intramuscular vaccines is considered with regard to known immunological mechanisms. Finally, we enumerate the population-level effects of approved vaccines on transmission through observational studies following clinical trials and vaccine distribution in real-world settings.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , COVID-19/transmission , Antibodies, Viral/biosynthesis , Antibodies, Viral/immunology , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Humans , Immunoglobulin A/biosynthesis , Immunoglobulin A/immunology , Immunoglobulin G/biosynthesis , Immunoglobulin G/immunology , Virus Replication/immunology
2.
Lancet Infect Dis ; 22(2): e52-e58, 2022 02.
Article in English | MEDLINE | ID: covidwho-1413176

ABSTRACT

As the number of individuals vaccinated against SARS-CoV-2 rises worldwide, population-level data regarding the vaccines' ability to reduce infection are being generated. Randomised trials have shown that these vaccines dramatically reduce symptomatic COVID-19; however, less is known about their effects on transmission between individuals. The natural course of infection with SARS-CoV-2 involves infection of the respiratory epithelia and replication within the mucosa to sufficient viral titres for transmission via aerosol particles and droplets. Here we discuss the available data on the existing, approved SARS-CoV-2 vaccines' capacity to reduce transmissibility by reducing primary infection, viral replication, capacity for transmission, and symptomaticity. The potential for mucosal-targeted SARS-CoV-2 vaccine strategies to more effectively limit transmission than intramuscular vaccines is considered with regard to known immunological mechanisms. Finally, we enumerate the population-level effects of approved vaccines on transmission through observational studies following clinical trials and vaccine distribution in real-world settings.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , COVID-19/transmission , Antibodies, Viral/biosynthesis , Antibodies, Viral/immunology , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Humans , Immunoglobulin A/biosynthesis , Immunoglobulin A/immunology , Immunoglobulin G/biosynthesis , Immunoglobulin G/immunology , Virus Replication/immunology
3.
J Clin Invest ; 131(14)2021 07 15.
Article in English | MEDLINE | ID: covidwho-1311203

ABSTRACT

Novel mRNA-based vaccines have been proven to be powerful tools in combating the global pandemic caused by SARS-CoV-2, with BNT162b2 (trade name: Comirnaty) efficiently protecting individuals from COVID-19 across a broad age range. Still, it remains largely unknown how renal insufficiency and immunosuppressive medication affect development of vaccine-induced immunity. We therefore comprehensively analyzed humoral and cellular responses in kidney transplant recipients after the standard second vaccination dose. As opposed to all healthy vaccinees and the majority of hemodialysis patients, only 4 of 39 and 1 of 39 transplanted individuals showed IgA and IgG seroconversion at day 8 ± 1 after booster immunization, with minor changes until day 23 ± 5, respectively. Although most transplanted patients mounted spike-specific T helper cell responses, frequencies were significantly reduced compared with those in controls and dialysis patients and this was accompanied by a broad impairment in effector cytokine production, memory differentiation, and activation-related signatures. Spike-specific CD8+ T cell responses were less abundant than their CD4+ counterparts in healthy controls and hemodialysis patients and almost undetectable in transplant patients. Promotion of anti-HLA antibodies or acute rejection was not detected after vaccination. In summary, our data strongly suggest revised vaccination approaches in immunosuppressed patients, including individual immune monitoring for protection of this vulnerable group at risk of developing severe COVID-19.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/immunology , COVID-19/prevention & control , Kidney Transplantation/adverse effects , SARS-CoV-2 , Adult , Aged , Antibodies, Viral/biosynthesis , COVID-19 Vaccines/immunology , Case-Control Studies , Cohort Studies , Cytokines/immunology , Female , Humans , Immunity, Cellular , Immunity, Humoral , Immunization, Secondary , Immunoglobulin A/biosynthesis , Immunoglobulin G/biosynthesis , Immunologic Memory , Immunosuppressive Agents/adverse effects , Lymphocyte Activation , Male , Middle Aged , Monitoring, Immunologic , Renal Dialysis/adverse effects , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology , Transplantation Immunology
4.
PLoS One ; 16(7): e0253977, 2021.
Article in English | MEDLINE | ID: covidwho-1295521

ABSTRACT

SARS-CoV-2 pandemic is causing high morbidity and mortality burden worldwide with unprecedented strain on health care systems. To investigate the time course of the antibody response in relation to the outcome we performed a study in hospitalized COVID-19 patients. As comparison we also investigated the time course of the antibody response in SARS-CoV-2 asymptomatic subjects. Study results show that patients produce a strong antibody response to SARS-CoV-2 with high correlation between different viral antigens (spike protein and nucleoprotein) and among antibody classes (IgA, IgG, and IgM and neutralizing antibodies). The antibody peak is reached by 3 weeks from hospital admission followed by a sharp decrease. No difference was observed in any parameter of the antibody classes, including neutralizing antibodies, between subjects who recovered or with fatal outcome. Only few asymptomatic subjects developed antibodies at detectable levels.


Subject(s)
Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , Asymptomatic Infections , COVID-19/immunology , SARS-CoV-2/immunology , Aged , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/mortality , Comorbidity , Female , Hospitalization , Humans , Immunoglobulin A/biosynthesis , Immunoglobulin A/blood , Immunoglobulin A/immunology , Immunoglobulin G/biosynthesis , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/biosynthesis , Immunoglobulin M/blood , Immunoglobulin M/immunology , Length of Stay , Male , Middle Aged , Patient Admission , Retrospective Studies
5.
Mol Cells ; 44(6): 392-400, 2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1249738

ABSTRACT

It has been more than a year since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged. Many studies have provided insights into the various aspects of the immune response in coronavirus disease 2019 (COVID-19). Especially for antibody treatment and vaccine development, humoral immunity to SARS-CoV-2 has been studied extensively, though there is still much that is unknown and controversial. Here, we introduce key discoveries on the humoral immune responses in COVID-19, including the immune dynamics of antibody responses and correlations with disease severity, neutralizing antibodies and their cross-reactivity, how long the antibody and memory B-cell responses last, aberrant autoreactive antibodies generated in COVID-19 patients, and the efficacy of currently available therapeutic antibodies and vaccines against circulating SARS-CoV-2 variants, and highlight gaps in the current knowledge.


Subject(s)
Antibodies, Neutralizing/biosynthesis , B-Lymphocytes/immunology , COVID-19/immunology , Immunoglobulin Class Switching , Immunoglobulin G/biosynthesis , SARS-CoV-2/pathogenicity , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/biosynthesis , Antibody-Dependent Enhancement , Autoantibodies/biosynthesis , B-Lymphocytes/virology , COVID-19/drug therapy , COVID-19/mortality , COVID-19/virology , Host-Pathogen Interactions/immunology , Humans , Immunity, Humoral/drug effects , Immunoglobulin A/biosynthesis , Immunoglobulin M/biosynthesis , Immunologic Memory , SARS-CoV-2/immunology , Severity of Illness Index , Survival Analysis
6.
J Med Virol ; 93(2): 892-898, 2021 02.
Article in English | MEDLINE | ID: covidwho-1206802

ABSTRACT

Since its emergence in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into a global pandemic within a matter of months. While subunit vaccines are one of the prominent options for combating coronavirus disease 2019 (COVID-19), the immunogenicity of spike protein-based antigens remains unknown. When immunized in mice, the S1 domain induced much higher IgG and IgA antibody levels than the receptor-binding domain (RBD) and more efficiently neutralized SARS-CoV-2 when adjuvanted with alum. It is inferred that a large proportion of these neutralization epitopes are located in the S1 domain but outside the RBD and that some of these are spatial epitopes. This finding indicates that expression systems with posttranslational modification abilities are important to maintain the natural configurations of recombinant spike protein antigens and are critical for effective COVID-19 vaccines. Further, adjuvants prone to a Th1 response should be considered for S1-based subunit COVID-19 vaccines to reduce the potential risk of antibody-dependent enhancement of infection.


Subject(s)
Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , Antigens, Viral/immunology , COVID-19 Vaccines/biosynthesis , COVID-19/prevention & control , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adjuvants, Immunologic/administration & dosage , Alum Compounds/administration & dosage , Animals , Antigens, Viral/genetics , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Female , HEK293 Cells , Humans , Immunity, Humoral/drug effects , Immunization , Immunization Schedule , Immunogenicity, Vaccine , Immunoglobulin A/biosynthesis , Immunoglobulin G/biosynthesis , Mice , Mice, Inbred BALB C , Protein Domains/immunology , Recombinant Proteins/administration & dosage , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Spike Glycoprotein, Coronavirus/genetics , Th1 Cells/drug effects , Th1 Cells/immunology , Th2 Cells/drug effects , Th2 Cells/immunology
7.
J Med Virol ; 93(2): 892-898, 2021 02.
Article in English | MEDLINE | ID: covidwho-661060

ABSTRACT

Since its emergence in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into a global pandemic within a matter of months. While subunit vaccines are one of the prominent options for combating coronavirus disease 2019 (COVID-19), the immunogenicity of spike protein-based antigens remains unknown. When immunized in mice, the S1 domain induced much higher IgG and IgA antibody levels than the receptor-binding domain (RBD) and more efficiently neutralized SARS-CoV-2 when adjuvanted with alum. It is inferred that a large proportion of these neutralization epitopes are located in the S1 domain but outside the RBD and that some of these are spatial epitopes. This finding indicates that expression systems with posttranslational modification abilities are important to maintain the natural configurations of recombinant spike protein antigens and are critical for effective COVID-19 vaccines. Further, adjuvants prone to a Th1 response should be considered for S1-based subunit COVID-19 vaccines to reduce the potential risk of antibody-dependent enhancement of infection.


Subject(s)
Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , Antigens, Viral/immunology , COVID-19 Vaccines/biosynthesis , COVID-19/prevention & control , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adjuvants, Immunologic/administration & dosage , Alum Compounds/administration & dosage , Animals , Antigens, Viral/genetics , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Female , HEK293 Cells , Humans , Immunity, Humoral/drug effects , Immunization , Immunization Schedule , Immunogenicity, Vaccine , Immunoglobulin A/biosynthesis , Immunoglobulin G/biosynthesis , Mice , Mice, Inbred BALB C , Protein Domains/immunology , Recombinant Proteins/administration & dosage , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Spike Glycoprotein, Coronavirus/genetics , Th1 Cells/drug effects , Th1 Cells/immunology , Th2 Cells/drug effects , Th2 Cells/immunology
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