Mechanisms of Rhinovirus Neutralisation by Antibodies.
Ontology highlight
ABSTRACT:
SUBMITTER: Touabi L
PROVIDER: S-EPMC7996599 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Ebolaviruses continue to pose a significant outbreak threat, and while Ebola virus (EBOV)-specific vaccines and antivirals have been licensed, efforts to develop candidates offering broad species cross-protection are continuing. The use of pseudotyped virus in place of live virus is recognised as an alternative, safer, high-throughput platform to evaluate anti-ebolavirus antibodies towards their development, yet it requires optimisation. Here, we have shown that the target cell line impacts neutralisation assay results and cannot be selected purely based on permissiveness. In expanding the platform to incorporate each of the ebolavirus species envelope glycoprotein, allowing a comprehensive assessment of cross-neutralisation, we found that the recently discovered Bombali virus has a point mutation in the receptor-binding domain which prevents entry into a hamster cell line and, importantly, shows that this virus can be cross-neutralised by EBOV antibodies and convalescent plasma.
| S-EPMC8412100 | biostudies-literature
Project description: Not available
| S-EPMC9179126 | biostudies-literature
Project description:Antibodies binding to the surface of virions can lead to virus neutralisation. Different theories have been proposed to determine the number of antibodies that must bind to a virion for neutralisation. Early models are based on chemical binding kinetics. Applying these models lead to very low estimates of the number of antibodies needed for neutralisation. In contrast, according to the more conceptual approach of stoichiometries in virology a much higher number of antibodies is required for virus neutralisation by antibodies. Here, we combine chemical binding kinetics with (virological) stoichiometries to better explain virus neutralisation by antibody binding. This framework is in agreement with published data on the neutralisation of the human immunodeficiency virus. Knowing antibody reaction constants, our model allows us to estimate stoichiometrical parameters from kinetic neutralisation curves. In addition, we can identify important parameters that will make further analysis of kinetic neutralisation curves more valuable in the context of estimating stoichiometries. Our model gives a more subtle explanation of kinetic neutralisation curves in terms of single-hit and multi-hit kinetics.
| S-EPMC3585397 | biostudies-literature
Project description:Abstract Serum levels of IgG, IgM and IgA against severe acute respiratory distress syndrome (SARS)-associated coronavirus (SARS-CoV) were detected serially with the use of immunofluorescent antibody assays in 30 patients with SARS. Seroconversion for IgG (mean 10 days) occurred simultaneously, or 1 day earlier, than that for IgM and IgA (mean 11 days for both). IgG could be detected as early as 4 days after the onset of illness. The earliest time at which these three antibodies reached peak levels was similar (mean 15 days). A high IgG level (1:800) could persist for > 3 months. The kinetics of neutralisation antibodies obtained with 100x the tissue culture infective dose (TCID50) of the SARS-CoV TW1 strain in five patients with SARS nearly paralleled those for IgG. There were no significant differences in the kinetics of the IgG, IgM and IgA responses between patients with or without underlying medical disease, steroid or intravenous immunoglobulin therapy, or mechanical ventilation.
| S-EPMC7129952 | biostudies-literature
Project description:The existence of multiple serotypes renders vaccine development challenging for most viruses in the Enterovirus genus. An alternative and potentially more viable strategy for control of these viruses is to develop broad-spectrum antivirals by targeting highly conserved proteins that are indispensable for the virus life cycle, such as the 3C protease. Previously, two single-chain antibody fragments, YDF and GGVV, were reported to effectively inhibit human rhinovirus 14 proliferation. Here, we found that both single-chain antibody fragments target sites on the 3C protease that are distinct from its known drug site (peptidase active site) and possess different mechanisms of inhibition. YDF does not block the active site but instead noncompetitively inhibits 3C peptidase activity through an allosteric effect that is rarely seen for antibody protease inhibitors. Meanwhile, GGVV antagonizes the less-explored regulatory function of 3C in genome replication. The interaction between 3C and the viral genome 5' noncoding region has been reported to be important for enterovirus genome replication. Here, the interface between human rhinovirus 14 3C and its 5' noncoding region was probed by hydrogen-deuterium exchange coupled mass spectrometry and found to partially overlap with the interface between GGVV and 3C. Consistently, prebinding of GGVV completely abolishes interaction between human rhinovirus 14 3C and its 5' noncoding region. The epitopes of YDF and GGVV, therefore, represent two additional sites of therapeutic vulnerability in rhinovirus. Importantly, the GGVV epitope appears to be conserved across many enteroviruses, suggesting that it is a promising target for pan-enterovirus inhibitor screening and design.
| S-EPMC7306783 | biostudies-literature
Project description:Rhinoviruses (RVs) are major causes of the common cold, but they can also trigger exacerbations of asthma. More than 160 different RV strains exist and can be classified into three genetic species (RV-A, RV-B and RV-C) which bind to different receptors on human cells including intracellular adhesion molecule 1 (ICAM-1), the low-density lipoprotein receptor (LDLR) or the cadherin-related family member 3 (CDHR3). Epitopes located in the RV capsid have mainly been determined for RV2, a minor-group RV-A strain binding to LDLR, and for RV14, a major-group RV-B strain binding to ICAM-1. In order to study epitopes involved in the neutralization of RV89, an ICAM-1-binding RV-A strain which is highly different from RV2 and RV14 in terms of receptor specificity and sequence, respectively, we analyzed the specificity and epitopes of a highly neutralizing antiserum using recombinantly produced RV89 capsid proteins (VP1, VP2, VP3 and VP4), recombinant fragments and synthetic overlapping peptides thereof. We found that the antiserum which neutralized in vitro RV89 infection up to a dilution of 1:24,000 reacted with the capsid proteins VP1 and VP2 but not with VP3 and VP4. The neutralizing antibodies recognized recombinant fragments comprising approximately 100 amino acids of the N- and C-terminus of VP1 and the middle part of VP2, in particular, three peptides which, according to molecular modeling based on the three-dimensional structure of RV16, were surface-exposed on the viral capsid. Two recombinant fusion proteins containing the identified peptides fused to hepatitis B (HBV)-derived preS as a carrier protein induced upon immunization of rabbits antibodies capable of neutralizing in vitro RV89 infections. Interestingly, the virus-neutralizing epitopes determined for RV89 corresponded to those determined for minor-group RV2 binding to LDL and major-group RV14 belonging to the RV-B species, which are highly different from RV89. Our results indicate that highly different RV strains, even when reacting with different receptors, seem to engage similar parts of their capsid in the infection process. These results may be important for the design of active and passive immunization strategies for RV.
| S-EPMC9100655 | biostudies-literature
Project description:IntroductionSince the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), substantial effort has been made to gain knowledge about the immunity elicited by infection or vaccination.MethodsWe studied the kinetics of antibodies and virus neutralisation induced by vaccination with BNT162b2 in a Swiss cohort of SARS-CoV-2 naïve (n = 40) and convalescent (n = 9) persons. Blood sera were analysed in a live virus neutralisation assay and specific IgG and IgA levels were measured by enzyme-linked immunoassay and analysed by descriptive statistics.ResultsVirus neutralisation was detected in all individuals 2-4 weeks after the second vaccine. Both neutralisation and antibodies remained positive for >4 months. Neutralisation and antibodies showed positive correlation, but immunoglobulin G (IgG) and immunoglobulin A (IgA) seroconversion took place 2-4 weeks faster than neutralisation. Spike-protein specific IgG levels rose significantly faster and were more stable over time than virus neutralisation titres or IgA responses. For naïve but not convalescent persons, a clear boosting effect was observed. Convalescent individuals showed faster, more robust and longer-lasting immune responses after vaccination compared to noninfected persons. No threshold could be determined for spike protein-specific IgG or IgA that would confer protection in the neutralisation assay, implicating the need for a better correlate of protection then antibody titres alone.ConclusionsThis study clearly shows the complex translation of antibody data and virus neutralisation, while supporting the evidence of a single dose being sufficient for effective antibody response in convalescent individuals.
| S-EPMC8926495 | biostudies-literature
Project description:BackgroundRhinoviruses (RVs) are a major cause of common colds and induce exacerbations of asthma and chronic inflammatory lung diseases.MethodsWe expressed and purified recombinant RV coat proteins VP1-4, non-structural proteins as well as N-terminal fragments of VP1 from four RV strains (RV14, 16, 89, C) covering the three known RV groups (RV-A, RV-B and RV-C) and measured specific IgG-subclass-, IgA- and IgM-responses by ELISA in subjects with different severities of asthma or without asthma before and after experimental infection with RV16.FindingsBefore infection subjects showed IgG1 > IgA > IgM > IgG3 cross-reactivity with N-terminal fragments from the representative VP1 proteins of the three RV groups. Antibody levels were higher in the asthmatic group as compared to the non-asthmatic subjects. Six weeks after infection with RV16, IgG1 antibodies showed a group-specific increase towards the N-terminal VP1 fragment, but not towards other capsid and non-structural proteins, which was highest in subjects with severe upper and lower respiratory symptoms.InterpretationOur results demonstrate that increases of antibodies towards the VP1 N-terminus are group-specific and associated with severity of respiratory symptoms and suggest that it may be possible to develop serological tests for identifying causative RV groups.
| S-EPMC4484518 | biostudies-literature
Project description:A pseudovirion-based neutralisation assay (PBNA) has been considered the gold standard for measuring specific antibody responses against human papillomavirus (HPV). However, this assay is labor intensive and therefore very difficult to implement in large-scale studies. Previous studies have evaluated the agreement between virus-like particle (VLP)-based ELISA and PBNA for measuring HPV vaccine-induced antibodies. However, the concordance of these assays to detect antibodies induced by natural infection has not yet been fully elucidated. In this study, the results of an Escherichia coli (E. coli)-expressed VLP-based ELISA were found to be highly concordant with those of a baculovirus-expressed VLP-based ELISA (r = 0.96 and 0.97 for HPV-16 and HPV-18) when detecing HPV vaccine induced antibodies and the concordance was medium (r = 0.68 and 0.68 for HPV-16 and HPV-18) when assessing natural infection induced antibodies. The results of the E. coli expressed VLP-based ELISA correlated well with those of the PBNA when testing 1020 post-vaccination human sera collected at one month after vaccination with the E. coli expressed VLP-based bivalent HPV vaccine (r = 0.83 and 0.81 for HPV-16 and HPV-18). The agreement and correlation were moderate (kappa<0.3 for both HPV types 16 and 18, r = 0.59 and 0.68 for HPV-16 and HPV-18, respectively) when assessing 1600 serum samples from unvaccinated women of age 18-25 years. In conclusion, the VLP-based ELISA is an acceptable surrogate for the neutralizing antibody assay in measuring vaccine responses. However, the use of the VLP-based ELISA in epidemiological studies should be carefully considered.
| S-EPMC4130265 | biostudies-literature
Project description:Coinfection by heterologous viruses in the respiratory tract is common and can alter disease severity compared to infection by individual virus strains. We previously found that inoculation of mice with rhinovirus (RV) 2 days before inoculation with a lethal dose of influenza A virus [A/Puerto Rico/8/34 (H1N1) (PR8)] provides complete protection against mortality. Here, we extended that finding to a second lethal respiratory virus, pneumonia virus of mice (PVM), and analyzed potential mechanisms of RV-induced protection. RV completely prevented mortality and weight loss associated with PVM infection. Major changes in host gene expression upon PVM infection were delayed compared to PR8. RV induced earlier recruitment of inflammatory cells, which were reduced at later times in RV-inoculated mice. Findings common to both virus pairs included the upregulated expression of mucin-associated genes and dampening of inflammation-related genes in mice that were inoculated with RV before lethal virus infection. However, type I interferon (IFN) signaling was required for RV-mediated protection against PR8 but not PVM. IFN signaling had minor effects on PR8 replication and contributed to controlling neutrophilic inflammation and hemorrhagic lung pathology in RV/PR8-infected mice. These findings, combined with differences in virus replication levels and disease severity, suggest that the suppression of inflammation in RV/PVM-infected mice may be due to early, IFN-independent suppression of viral replication, while that in RV/PR8-infected mice may be due to IFN-dependent modulation of immune responses. Thus, a mild upper respiratory viral infection can reduce the severity of a subsequent severe viral infection in the lungs through virus-dependent mechanisms. IMPORTANCE Respiratory viruses from diverse families cocirculate in human populations and are frequently detected within the same host. Although clinical studies suggest that infection by multiple different respiratory viruses may alter disease severity, animal models in which we can control the doses, timing, and strains of coinfecting viruses are critical to understanding how coinfection affects disease severity. Here, we compared gene expression and immune cell recruitment between two pairs of viruses (RV/PR8 and RV/PVM) inoculated sequentially in mice, both of which result in reduced severity compared to lethal infection by PR8 or PVM alone. Reduced disease severity was associated with suppression of inflammatory responses in the lungs. However, differences in disease kinetics and host and viral gene expression suggest that protection by coinfection with RV may be due to distinct molecular mechanisms. Indeed, we found that antiviral cytokine signaling was required for RV-mediated protection against lethal infection by PR8 but not PVM.
| S-EPMC8265665 | biostudies-literature