scholarly journals Cross-reactive antibodies against human coronaviruses and the animal coronavirome suggest diagnostics for future zoonotic spillovers

2021 ◽  
Vol 6 (61) ◽  
pp. eabe9950
Author(s):  
Shelley Klompus ◽  
Sigal Leviatan ◽  
Thomas Vogl ◽  
Roei D. Mazor ◽  
Iris N. Kalka ◽  
...  
Keyword(s):  
Early Stage ◽  
Cross Reactivity ◽  
Antibody Binding ◽  
Antibody Responses ◽  
Diagnostic Strategy ◽  
Binding Data ◽  
Antibody Repertoires ◽  
Human Coronaviruses ◽  
Reactive Antibody ◽  
Shared Motif

The spillover of animal coronaviruses (aCoVs) to humans has caused SARS, MERS, and COVID-19. While antibody responses displaying cross-reactivity between SARS-CoV-2 and seasonal/common cold human coronaviruses (hCoVs) have been reported, potential cross-reactivity with aCoVs and the diagnostic implications are incompletely understood. Here, we probed for antibody binding against all seven hCoVs and 49 aCoVs represented as 12,924 peptides within a phage-displayed antigen library. Antibody repertoires of 269 recovered COVID-19 patients showed distinct changes compared to 260 unexposed pre-pandemic controls, not limited to binding of SARS-CoV-2 antigens but including binding to antigens from hCoVs and aCoVs with shared motifs to SARS-CoV-2. We isolated broadly reactive monoclonal antibodies from recovered COVID-19 patients that bind a shared motif of SARS-CoV-2, hCoV-OC43, hCoV-HKU1, and several aCoVs, demonstrating that interspecies cross-reactivity can be mediated by a single immunoglobulin. Employing antibody binding data against the entire CoV antigen library allowed accurate discrimination of recovered COVID-19 patients from unexposed individuals by machine learning. Leaving out SARS-CoV-2 antigens and relying solely on antibody binding to other hCoVs and aCoVs achieved equally accurate detection of SARS-CoV-2 infection. The ability to detect SARS-CoV-2 infection without knowledge of its unique antigens solely from cross-reactive antibody responses against other hCoVs and aCoVs suggests a potential diagnostic strategy for the early stage of future pandemics. Creating regularly updated antigen libraries representing the animal coronavirome can provide the basis for a serological assay already poised to identify infected individuals following a future zoonotic transmission event.

scholarly journals Cross-reactive antibody responses against SARS-CoV-2 and seasonal common cold coronaviruses

2020 ◽  
Author(s):  
Shelley Klompus ◽  
Sigal Leviatan ◽  
Thomas Vogl ◽  
Iris Kalka ◽  
Anastasia Godneva ◽  
...  
Keyword(s):  
T Cells ◽  
High Resolution ◽  
Common Cold ◽  
Interindividual Variability ◽  
Serum Antibody ◽  
Cross Reactivity ◽  
Antibody Responses ◽  
Antibody Repertoires ◽  
High Throughput Assay ◽  
Reactive Antibody

Beyond SARS-CoV-2, six more coronaviruses infect humans (hCoVs), four of which cause only mild symptoms (seasonal/common cold hCoVs). Previous exposures to seasonal hCoVs may elicit immunological memory that could benefit the course of SARS-CoV-2 infections. While cross-reactive T cells epitopes of SARS-CoV-2 and seasonal hCoVs have been reported in individuals unexposed to SARS-CoV-2, potential antibody-based cross-reactivity is incompletely understood. Here, we have probed for high resolution antibody binding against all hCoVs represented as 1,539 peptides with a phage-displayed antigen library. We detected broad serum antibody responses against peptides of seasonal hCoVs in up to 75% of individuals. Recovered COVID-19 patients exhibited distinct antibody repertoires targeting variable SARS-CoV-2 epitopes, and could be accurately classified from unexposed individuals (AUC=0.96). Up to 50% of recovered patients also mounted antibody responses against unique epitopes of seasonal hCoV-OC43, that were not detectable in unexposed individuals. These results indicate substantial interindividual variability and antibody cross-reactivity between hCoVs from the direction of SARS-CoV-2 infections towards seasonal hCoVs. Our accurate high throughput assay allows profiling preexisting antibody responses against seasonal hCoVs cost-effectively and could inform on their protective nature against SARS-CoV-2.

scholarly journals Waning antibody responses in COVID-19: what can we learn from the analysis of other coronaviruses?

Infection ◽  
2021 ◽  
Author(s):  
Ali Hamady ◽  
JinJu Lee ◽  
Zuzanna A. Loboda
Keyword(s):  
Cross Reactivity ◽  
Antibody Responses ◽  
The Novel ◽  
Incidence And Mortality ◽  
Antibody Titres ◽  
Human Coronaviruses ◽  
Public Health Strategies ◽  
Antibody Dynamics

Abstract Objectives The coronavirus disease 2019 (COVID-19), caused by the novel betacoronavirus severe acute respiratory syndrome 2 (SARS-CoV-2), was declared a pandemic in March 2020. Due to the continuing surge in incidence and mortality globally, determining whether protective, long-term immunity develops after initial infection or vaccination has become critical. Methods/Results In this narrative review, we evaluate the latest understanding of antibody-mediated immunity to SARS-CoV-2 and to other coronaviruses (SARS-CoV, Middle East respiratory syndrome coronavirus and the four endemic human coronaviruses) in order to predict the consequences of antibody waning on long-term immunity against SARS-CoV-2. We summarise their antibody dynamics, including the potential effects of cross-reactivity and antibody waning on vaccination and other public health strategies. At present, based on our comparison with other coronaviruses we estimate that natural antibody-mediated protection for SARS-CoV-2 is likely to last for 1–2 years and therefore, if vaccine-induced antibodies follow a similar course, booster doses may be required. However, other factors such as memory B- and T-cells and new viral strains will also affect the duration of both natural and vaccine-mediated immunity. Conclusion Overall, antibody titres required for protection are yet to be established and inaccuracies of serological methods may be affecting this. We expect that with standardisation of serological testing and studies with longer follow-up, the implications of antibody waning will become clearer.

scholarly journals Adenovirus Type 4 and 7 Vaccination or Adenovirus Type 4 Respiratory Infection Elicits Minimal Cross-Reactive Antibody Responses to Nonhuman Adenovirus Vaccine Vectors

2014 ◽  
Vol 21 (5) ◽  
pp. 783-786 ◽  
Author(s):  
Robert Paris ◽  
Robert A. Kuschner ◽  
Leonard Binn ◽  
Stephen J. Thomas ◽  
Stefano Colloca ◽  
...  
Keyword(s):  
Respiratory Infection ◽  
Neutralizing Antibodies ◽  
Adenovirus Vector ◽  
Adenovirus Type ◽  
Cross Reactivity ◽  
Antibody Responses ◽  
Vaccine Vectors ◽  
Adenovirus Vaccine ◽  
Reactive Antibody

ABSTRACTAntivector immunity may limit the immunogenicity of adenovirus vector vaccines. We tested sera from individuals immunized with adenovirus type 4 and 7 (Ad4 and Ad7, respectively) vaccine or naturally infected with Ad4 for their ability to neutralize a panel of E1-deleted human and chimpanzee adenoviruses (ChAd). Small statistically significant increases in titers to ChAd63, ChAd3, human Ad35, and human Ad5 were observed. Neutralizing antibodies elicited by Ad4 infection or immunization results in a small amount of adenovirus cross-reactivity.

scholarly journals Peptide microarray based analysis of antibody responses to SARS-CoV-2 identifies unique epitopes with potential for diagnostic test development

2020 ◽  
Author(s):  
Pavlo Holenya ◽  
Paul Joris Lange ◽  
Ulf Reimer ◽  
Wolfram Woltersdorf ◽  
Thomas Panterodt ◽  
...  
Keyword(s):  
Diagnostic Test ◽  
Humoral Immunity ◽  
Cross Reactivity ◽  
Antibody Responses ◽  
Immune Protection ◽  
Peptide Microarrays ◽  
Igg Binding ◽  
Human Coronaviruses ◽  
Antibody Tests ◽  
Control Samples

SummaryHumoral immunity to the Severe Adult Respiratory Syndrome (SARS) Coronavirus (CoV)-2 is not fully understood yet but may be a crucial factor of immune protection. The possibility of antibody cross-reactivity between SARS-CoV-2 and other human coronaviruses (HCoVs) would have important implications for immune protection but also for the development of specific diagnostic ELISA tests. Using peptide microarrays, n=24 patient samples and n=12 control samples were screened for antibodies against the entire SARS-CoV-2 proteome as well as the Spike (S), Nucleocapsid (N), VME1 (V), R1ab, and Protein 3a (AP3A) of the HCoV strains SARS, MERS, OC43 and 229E. While widespread cross-reactivity was revealed across several immunodominant regions of S and N, IgG binding to several SARS-CoV-2-derived peptides provided statistically significant discrimination between COVID-19 patients and controls. Selected target peptides may serve as capture antigens for future, highly COVID-19-specific diagnostic antibody tests.

scholarly journals Human Survivors of Disease Outbreaks Caused by Ebola or Marburg Virus Exhibit Cross-Reactive and Long-Lived Antibody Responses

2016 ◽  
Vol 23 (8) ◽  
pp. 717-724 ◽  
Author(s):  
Mohan Natesan ◽  
Stig M. Jensen ◽  
Sarah L. Keasey ◽  
Teddy Kamata ◽  
Ana I. Kuehne ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protein Microarray ◽  
Disease Outbreaks ◽  
Cross Reactivity ◽  
Marburg Virus ◽  
Antibody Responses ◽  
Diagnostic Methods ◽  
Virus Infections ◽  
Content Type ◽  
Reactive Antibody

ABSTRACTA detailed understanding of serological immune responses to Ebola and Marburg virus infections will facilitate the development of effective diagnostic methods, therapeutics, and vaccines. We examined antibodies from Ebola or Marburg survivors 1 to 14 years after recovery from disease, by using a microarray that displayed recombinant nucleoprotein (NP), viral protein 40 (VP40), envelope glycoprotein (GP), and inactivated whole virions from six species of filoviruses. All three outbreak cohorts exhibited significant antibody responses to antigens from the original infecting species and a pattern of additional filoviruses that varied by outbreak. NP was the most cross-reactive antigen, while GP was the most specific. Antibodies from survivors of infections byMarburg marburgvirus(MARV) species were least cross-reactive, while those from survivors of infections bySudan virus(SUDV) species exhibited the highest cross-reactivity. Based on results revealed by the protein microarray, persistent levels of antibodies to GP, NP, and VP40 were maintained for up to 14 years after infection, and survival of infection caused by one species imparted cross-reactive antibody responses to other filoviruses.

scholarly journals Distinct antibody repertoires against endemic human coronaviruses in children and adults

2020 ◽  
Author(s):  
Taushif Khan ◽  
Mahbuba Rahman ◽  
Fatima Al Ali ◽  
Susie S. Y. Huang ◽  
Manar Ata ◽  
...  
Keyword(s):  
B Cell ◽  
Antibody Responses ◽  
Human Antibody ◽  
Cell Responses ◽  
Coronavirus Infection ◽  
Antibody Repertoires ◽  
Human Coronaviruses ◽  
Antibody Specificities ◽  
Species Specific ◽  
Therapeutic Monoclonal Antibodies

AbstractFour endemic human coronaviruses (HCoVs) are commonly associated with acute respiratory infection in humans. B cell responses to these “common cold” viruses remain incompletely understood. Here we report a comprehensive analysis of CoV-specific antibody repertoires in 231 children and 1168 adults using phage-immunoprecipitation sequencing. Seroprevalence of antibodies to endemic HCoVs ranged between ~4 and 27% depending on the species and cohort. We identified at least 136 novel linear B cell epitopes. Antibody repertoires against endemic HCoVs were qualitatively different between children and adults in that anti-HCoV IgG specificities more frequently found among children targeted functionally important and structurally conserved regions of the spike, nucleocapsid and matrix proteins. Moreover, antibody specificities targeting the highly conserved fusion peptide region and S2’ cleavage site of the spike protein were broadly cross-reactive with peptides of epidemic human and non-human coronaviruses. In contrast, an acidic tandem repeat in the N-terminal region of the Nsp3 subdomain of the HCoV-HKU1 polyprotein was the predominant target of antibody responses in adult donors. Our findings shed light on the dominant species-specific and pan-CoV target sites of human antibody responses to coronavirus infection, thereby providing important insights for the development of prophylactic or therapeutic monoclonal antibodies and vaccine design.

scholarly journals Cross-reactive antibody response between SARS-CoV-2 and SARS-CoV infections

2020 ◽  
Author(s):  
Huibin Lv ◽  
Nicholas C. Wu ◽  
Owen Tak-Yin Tsang ◽  
Meng Yuan ◽  
Ranawaka A. P. M. Perera ◽  
...  
Keyword(s):  
Antibody Response ◽  
Vaccine Development ◽  
Neutralizing Antibody ◽  
Cross Reactivity ◽  
Antibody Responses ◽  
World Health ◽  
Cross Neutralization ◽  
Novel Coronavirus ◽  
Health Organization ◽  
Reactive Antibody

AbstractThe World Health Organization has recently declared the ongoing outbreak of COVID-19, which is caused by a novel coronavirus SARS-CoV-2, as pandemic. There is currently a lack of knowledge in the antibody response elicited from SARS-CoV-2 infection. One major immunological question is concerning the antigenic differences between SARS-CoV-2 and SARS-CoV. We address this question by using plasma from patients infected by SARS-CoV-2 or SARS-CoV, and plasma obtained from infected or immunized mice. Our results show that while cross-reactivity in antibody binding to the spike protein is common, cross-neutralization of the live viruses is rare, indicating the presence of non-neutralizing antibody response to conserved epitopes in the spike. Whether these non-neutralizing antibody responses will lead to antibody-dependent disease enhancement needs to be addressed in the future. Overall, this study not only addresses a fundamental question regarding the antigenicity differences between SARS-CoV-2 and SARS-CoV, but also has important implications in vaccine development.

scholarly journals Are the Enzyme Immunoassays for Antibodies to Pneumococcal Capsular Polysaccharides Serotype Specific?

2000 ◽  
Vol 7 (3) ◽  
pp. 468-476 ◽  
Author(s):  
Anu Soininen ◽  
Germie van den Dobbelsteen ◽  
Lukas Oomen ◽  
Helena Käyhty
Keyword(s):  
Cell Wall ◽  
Monoclonal Antibodies ◽  
Antibody Response ◽  
Enzyme Immunoassay ◽  
Tetanus Toxoid ◽  
Cross Reactivity ◽  
Antibody Binding ◽  
Pneumococcal Vaccines ◽  
Capsular Polysaccharides ◽  
Reactive Antibody

ABSTRACT The specificity of antibody binding to pneumococcal capsular polysaccharides (Pnc PSs) measured by enzyme immunoassay (EIA) was studied by inhibition of antibody binding by homologous and heterologous PSs. We found extensive cross-reactivity of antibody binding to type 6B, 19F, and 23F PSs but not to type 14 PS, even after treatment with cell wall PS (CPS). The cross-reactive antibody was highly prevalent in sera of infants and adults with naturally acquired antibody, but not in sera of infants and adults immunized with pneumococcal vaccines. However, a type 11A antibody response was seen after vaccination with heterologous PSs. Monoclonal antibodies prepared against a type 6B PS-tetanus toxoid conjugate recognized also other than the specific type of PS in the EIA, implying the possible existence of a cross-reactive epitope. Remarkable differences in specificity among type 6B PS preparations from different manufacturers were found. Moreover, different lots of type 11A PS from the same manufacturer showed differences in specificity. The results suggest that some Pnc PS preparations may contain cross-reactive epitopes or impurities, other than CPS, that are common to many types of Pnc PS. The specificity of antibodies, especially in sera from nonimmunized subjects, measured by EIA can be questioned.

scholarly journals An H7N1 Influenza Virus Vaccine Induces Broadly Reactive Antibody Responses against H7N9 in Humans

2014 ◽  
Vol 21 (8) ◽  
pp. 1153-1163 ◽  
Author(s):  
Florian Krammer ◽  
Åsne Jul-Larsen ◽  
Irina Margine ◽  
Ariana Hirsh ◽  
Haakon Sjursen ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Vaccine Trial ◽  
Neutralizing Antibody ◽  
Passive Transfer ◽  
Cross Reactivity ◽  
Influenza Viruses ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Reactive Antibody

ABSTRACTEmerging H7N9 influenza virus infections in Asia have once more spurred the development of effective prepandemic H7 vaccines. However, many vaccines based on avian influenza viruses—including H7—are poorly immunogenic, as measured by traditional correlates of protection. Here we reevaluated sera from an H7N1 human vaccine trial performed in 2006. We examined cross-reactive antibody responses to divergent H7 strains, including H7N9, dissected the antibody response into head- and stalk-reactive antibodies, and tested thein vivopotency of these human sera in a passive-transfer H7N9 challenge experiment with mice. Although only a low percentage of vaccinees induced neutralizing antibody responses against the homologous vaccine strain and also H7N9, we detected strong cross-reactivity to divergent H7 hemagglutinins (HAs) in a large proportion of the cohort with a quantitative enzyme-linked immunosorbent assay. Furthermore, H7N1 vaccination induced antibodies to both the head and stalk domains of the HA, which is in sharp contrast to seasonal inactivated vaccines. Finally, we were able to show that both neutralizing and nonneutralizing antibodies improvedin vivovirus clearance in a passive-transfer H7N9 challenge mouse model.

scholarly journals Homologous and heterologous antibodies to coronavirus 229E, NL63, OC43, HKU1, SARS, MERS and SARS-CoV-2 antigens in an age stratified cross-sectional serosurvey in a large tertiary hospital in The Netherlands

2020 ◽  
Author(s):  
Brenda M. Westerhuis ◽  
Erwin de Bruin ◽  
Felicity D Chandler ◽  
Chris R.B. Ramakers ◽  
Nisreen M.A. Okba ◽  
...  
Keyword(s):  
The Netherlands ◽  
Age Groups ◽  
Tertiary Hospital ◽  
Cross Reactivity ◽  
Antibody Responses ◽  
Cross Sectional ◽  
Erasmus Medical ◽  
Cross Sectional Studies ◽  
Human Coronaviruses ◽  
Species Specific

Understanding the coronavirus (CoV) antibody landscape in relation to disease and susceptibility is critical for modelling of steps in the next phase during the current covid-19 pandemic. In March 2020, during the first month of the epidemic in The Netherlands, we performed cross sectional studies at two time points amongst patients of the Erasmus Medical Centre in Rotterdam, to assess the presence of antibodies against seasonal human coronaviruses (OC43, 229E, NL63, HKU1), emerging zoonotic coronaviruses (SARS, MERS) and SARS-CoV-2 in nine different age groups. We observed minimal SARS-CoV-2 reactivity early March (0.7% of sera), increasing to 3.0%, four weeks later, suggesting probably undetected cases during this early phase of the epidemic. Antibody responses were mostly coronavirus species specific at young age, but possible cross-reactivity between human seasonal CoVs was observed with increasing age.

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