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1.
Nat Commun ; 12(1): 2670, 2021 05 11.
Article in English | MEDLINE | ID: covidwho-1225507

ABSTRACT

Understanding how antibody responses to SARS-CoV-2 evolve during infection may provide important insight into therapeutic approaches and vaccination for COVID-19. Here we profile the antibody responses of 162 COVID-19 symptomatic patients in the COVID-BioB cohort followed longitudinally for up to eight months from symptom onset to find SARS-CoV-2 neutralization, as well as antibodies either recognizing SARS-CoV-2 spike antigens and nucleoprotein, or specific for S2 antigen of seasonal beta-coronaviruses and hemagglutinin of the H1N1 flu virus. The presence of neutralizing antibodies within the first weeks from symptoms onset correlates with time to a negative swab result (p = 0.002), while the lack of neutralizing capacity correlates with an increased risk of a fatal outcome (p = 0.008). Neutralizing antibody titers progressively drop after 5-8 weeks but are still detectable up to 8 months in the majority of recovered patients regardless of age or co-morbidities, with IgG to spike antigens providing the best correlate of neutralization. Antibody responses to seasonal coronaviruses are temporarily boosted, and parallel those to SARS-CoV-2 without dampening the specific response or worsening disease progression. Our results thus suggest compromised immune responses to the SARS-CoV-2 spike to be a major trait of COVID-19 patients with critical conditions, and thereby inform on the planning of COVID-19 patient care and therapy prioritization.


Subject(s)
Antibodies, Neutralizing/immunology , COVID-19/immunology , COVID-19/mortality , SARS-CoV-2/immunology , Aged , Antibodies, Viral/immunology , Antibody Formation , Betacoronavirus/immunology , COVID-19/virology , Female , Humans , Immunoglobulin G/immunology , Kinetics , Longitudinal Studies , Male , Middle Aged , Neutralization Tests , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/immunology , Survival Rate
2.
Front Immunol ; 12: 654165, 2021.
Article in English | MEDLINE | ID: covidwho-1170087

ABSTRACT

In the year since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and with understanding of the etiology of the coronavirus disease 2019 (COVID-19) pandemic, it has become clear that most infected individuals achieve some form of immunity against the virus with relatively few reported reinfections. A number of vaccines have already achieved emergency use authorization based on data from large phase 3 field efficacy clinical trials. However, our knowledge about the extent and durability of this immunity, and the breadth of vaccine coverage against SARS-CoV-2 variants is still evolving. In this narrative review, we summarize the latest and rapidly developing understanding of immunity to SARS-CoV-2 infection, including what we have learned about the key antigens of SARS-CoV-2 (i.e., the spike protein and its receptor-binding domain), their importance in vaccine development, the immediate immune response to SARS-CoV-2, breadth of coverage of emerging SARS-CoV-2 variants, contributions of preexisting immunity to related coronaviruses, and duration of immunity. We also discuss lessons from newer approaches, such as systems serology, that provide insights into molecular and cellular immune responses elicited and how they relate to the trajectory of infection, and potentially inform immune correlates of protection. We also briefly examine the limited research literature on immune responses in special populations, such as pregnant women and children.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , COVID-19/physiopathology , Child , Female , Humans , Immunity, Cellular , Pandemics , Pregnancy , Pregnancy Complications, Infectious , Protein Domains , SARS-CoV-2/pathogenicity , T-Lymphocytes/immunology , Vaccination
3.
Lancet Microbe ; 2(2): e60-e69, 2021 02.
Article in English | MEDLINE | ID: covidwho-1065710

ABSTRACT

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces an antibody response targeting multiple antigens that changes over time. This study aims to take advantage of this complexity to develop more accurate serological diagnostics. METHODS: A multiplex serological assay was developed to measure IgG and IgM antibody responses to seven SARS-CoV-2 spike or nucleoprotein antigens, two antigens for the nucleoproteins of the 229E and NL63 seasonal coronaviruses, and three non-coronavirus antigens. Antibodies were measured in serum samples collected up to 39 days after symptom onset from 215 adults in four French hospitals (53 patients and 162 health-care workers) with quantitative RT-PCR-confirmed SARS-CoV-2 infection, and negative control serum samples collected from healthy adult blood donors before the start of the SARS-CoV-2 epidemic (335 samples from France, Thailand, and Peru). Machine learning classifiers were trained with the multiplex data to classify individuals with previous SARS-CoV-2 infection, with the best classification performance displayed by a random forests algorithm. A Bayesian mathematical model of antibody kinetics informed by prior information from other coronaviruses was used to estimate time-varying antibody responses and assess the sensitivity and classification performance of serological diagnostics during the first year following symptom onset. A statistical estimator is presented that can provide estimates of seroprevalence in very low-transmission settings. FINDINGS: IgG antibody responses to trimeric spike protein (Stri) identified individuals with previous SARS-CoV-2 infection with 91·6% (95% CI 87·5-94·5) sensitivity and 99·1% (97·4-99·7) specificity. Using a serological signature of IgG and IgM to multiple antigens, it was possible to identify infected individuals with 98·8% (96·5-99·6) sensitivity and 99·3% (97·6-99·8) specificity. Informed by existing data from other coronaviruses, we estimate that 1 year after infection, a monoplex assay with optimal anti-Stri IgG cutoff has 88·7% (95% credible interval 63·4-97·4) sensitivity and that a four-antigen multiplex assay can increase sensitivity to 96·4% (80·9-100·0). When applied to population-level serological surveys, statistical analysis of multiplex data allows estimation of seroprevalence levels less than 2%, below the false-positivity rate of many other assays. INTERPRETATION: Serological signatures based on antibody responses to multiple antigens can provide accurate and robust serological classification of individuals with previous SARS-CoV-2 infection. This provides potential solutions to two pressing challenges for SARS-CoV-2 serological surveillance: classifying individuals who were infected more than 6 months ago and measuring seroprevalence in serological surveys in very low-transmission settings. FUNDING: European Research Council. Fondation pour la Recherche Médicale. Institut Pasteur Task Force COVID-19.


Subject(s)
COVID-19 , Adult , Antibodies, Viral , Bayes Theorem , COVID-19/diagnosis , Humans , Immunoglobulin G , Immunoglobulin M , Machine Learning , SARS-CoV-2 , Sensitivity and Specificity , Seroepidemiologic Studies
4.
Nat Commun ; 11(1): 2601, 2020 05 20.
Article in English | MEDLINE | ID: covidwho-326048

ABSTRACT

The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for the pandemic viral pneumonia disease, COVID-19. At this time, no vaccine is available to control further dissemination of the disease. We have previously engineered a synthetic DNA vaccine targeting the MERS coronavirus Spike (S) protein, the major surface antigen of coronaviruses, which is currently in clinical study. Here we build on this prior experience to generate a synthetic DNA-based vaccine candidate targeting SARS-CoV-2 S protein. The engineered construct, INO-4800, results in robust expression of the S protein in vitro. Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further translational study.


Subject(s)
Antigens, Viral/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccines, DNA/immunology , Viral Vaccines/immunology , Angiotensin-Converting Enzyme 2 , Animals , Antibodies, Neutralizing/immunology , Antigens, Viral/chemistry , COVID-19 Vaccines , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Epitope Mapping , Guinea Pigs , Immunity, Humoral , Immunoglobulin G/immunology , Lung/immunology , Mice , Mice, Inbred BALB C , Middle East Respiratory Syndrome Coronavirus , Models, Animal , Peptidyl-Dipeptidase A/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Viral Vaccines/chemistry
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