In Vitro Enhancement of Respiratory Syncytial Virus Infection by Maternal Antibodies Does Not Explain Disease Severity in Infants.

2.50
Hdl Handle:
http://hdl.handle.net/10029/621061
Title:
In Vitro Enhancement of Respiratory Syncytial Virus Infection by Maternal Antibodies Does Not Explain Disease Severity in Infants.
Authors:
van Erp, Elisabeth A; van Kasteren, Puck B; Guichelaar, Teun; Ahout, Inge M L; de Haan, Cornelis A M; Luytjes, Willem; Ferwerda, Gerben; Wicht, Oliver
Abstract:
Respiratory syncytial virus (RSV) is the leading cause of severe respiratory illness in infants. At this young age, infants typically depend on maternally transferred antibodies (matAbs) and their innate immune system for protection against infections. RSV-specific matAbs are thought to protect from severe illness, yet severe RSV disease occurs mainly below 6 months of age, when neutralizing matAb levels are present. To investigate this discrepancy, we asked if disease severity is related to antibody properties other than neutralization. Some antibody effector functions are mediated via their Fc binding region. However, it has been shown that this binding may lead to antibody-dependent enhancement (ADE) of infection or reduction of neutralization, both possibly leading to more disease. In this study, we first showed that high levels of ADE of RSV infection occur in monocytic THP-1 cells in the presence of RSV antibodies and that neutralization by these antibodies was reduced in Vero cells when they were transduced with Fc gamma receptors. We then demonstrated that antibodies from cotton rats with formalin-inactivated (FI)-RSV-induced pulmonary pathology were capable of causing ADE. Human matAbs also caused ADE and were less neutralizing in vitro in cells that carry Fc receptors. However, these effects were unrelated to disease severity because they were seen both in uninfected controls and in infants hospitalized with different levels of RSV disease severity. We conclude that ADE and reduction of neutralization are unlikely to be involved in RSV disease in infants with neutralizing matAbs.IMPORTANCE It is unclear why severity of RSV disease peaks at the age when infants have neutralizing levels of maternal antibodies. Additionally, the exact reason for FI-RSV-induced enhanced disease, as seen in the 1960s vaccine trials, is still unclear. We hypothesized that antibodies present under either of these conditions could contribute to disease severity. Antibodies can have effects that may lead to more disease instead of protection. We investigated two of those effects: antibody-dependent enhancement of infection (ADE) and neutralization reduction. We show that ADE occurs in vitro with antibodies from FI-RSV-immunized RSV-infected cotton rats. Moreover, passively acquired maternal antibodies from infants had the capacity to induce ADE and reduction of neutralization. However, no clear association with disease severity was seen, ruling out that these properties explain disease in the presence of maternal antibodies. Our data contribute to a better understanding of the impact of antibodies on RSV disease in infants.
Citation:
In Vitro Enhancement of Respiratory Syncytial Virus Infection by Maternal Antibodies Does Not Explain Disease Severity in Infants. 2017, 91 (21) J. Virol.
Journal:
J Virol 2017, 91(21). pii: e00851-17
Issue Date:
1-Nov-2017
URI:
http://hdl.handle.net/10029/621061
DOI:
10.1128/JVI.00851-17
PubMed ID:
28794038
Type:
Article
Language:
en
ISSN:
1098-5514
Appears in Collections:
Miscellaneous

Full metadata record

DC FieldValue Language
dc.contributor.authorvan Erp, Elisabeth Aen
dc.contributor.authorvan Kasteren, Puck Ben
dc.contributor.authorGuichelaar, Teunen
dc.contributor.authorAhout, Inge M Len
dc.contributor.authorde Haan, Cornelis A Men
dc.contributor.authorLuytjes, Willemen
dc.contributor.authorFerwerda, Gerbenen
dc.contributor.authorWicht, Oliveren
dc.date.accessioned2018-01-09T12:22:37Z-
dc.date.available2018-01-09T12:22:37Z-
dc.date.issued2017-11-01-
dc.identifier.citationIn Vitro Enhancement of Respiratory Syncytial Virus Infection by Maternal Antibodies Does Not Explain Disease Severity in Infants. 2017, 91 (21) J. Virol.en
dc.identifier.issn1098-5514-
dc.identifier.pmid28794038-
dc.identifier.doi10.1128/JVI.00851-17-
dc.identifier.urihttp://hdl.handle.net/10029/621061-
dc.description.abstractRespiratory syncytial virus (RSV) is the leading cause of severe respiratory illness in infants. At this young age, infants typically depend on maternally transferred antibodies (matAbs) and their innate immune system for protection against infections. RSV-specific matAbs are thought to protect from severe illness, yet severe RSV disease occurs mainly below 6 months of age, when neutralizing matAb levels are present. To investigate this discrepancy, we asked if disease severity is related to antibody properties other than neutralization. Some antibody effector functions are mediated via their Fc binding region. However, it has been shown that this binding may lead to antibody-dependent enhancement (ADE) of infection or reduction of neutralization, both possibly leading to more disease. In this study, we first showed that high levels of ADE of RSV infection occur in monocytic THP-1 cells in the presence of RSV antibodies and that neutralization by these antibodies was reduced in Vero cells when they were transduced with Fc gamma receptors. We then demonstrated that antibodies from cotton rats with formalin-inactivated (FI)-RSV-induced pulmonary pathology were capable of causing ADE. Human matAbs also caused ADE and were less neutralizing in vitro in cells that carry Fc receptors. However, these effects were unrelated to disease severity because they were seen both in uninfected controls and in infants hospitalized with different levels of RSV disease severity. We conclude that ADE and reduction of neutralization are unlikely to be involved in RSV disease in infants with neutralizing matAbs.IMPORTANCE It is unclear why severity of RSV disease peaks at the age when infants have neutralizing levels of maternal antibodies. Additionally, the exact reason for FI-RSV-induced enhanced disease, as seen in the 1960s vaccine trials, is still unclear. We hypothesized that antibodies present under either of these conditions could contribute to disease severity. Antibodies can have effects that may lead to more disease instead of protection. We investigated two of those effects: antibody-dependent enhancement of infection (ADE) and neutralization reduction. We show that ADE occurs in vitro with antibodies from FI-RSV-immunized RSV-infected cotton rats. Moreover, passively acquired maternal antibodies from infants had the capacity to induce ADE and reduction of neutralization. However, no clear association with disease severity was seen, ruling out that these properties explain disease in the presence of maternal antibodies. Our data contribute to a better understanding of the impact of antibodies on RSV disease in infants.en
dc.language.isoenen
dc.rightsArchived with thanks to Journal of virologyen
dc.subject.meshAnimals-
dc.subject.meshAntibodies, Neutralizing-
dc.subject.meshAntibodies, Viral-
dc.subject.meshAntibody-Dependent Enhancement-
dc.subject.meshCase-Control Studies-
dc.subject.meshCercopithecus aethiops-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshInfant-
dc.subject.meshLung-
dc.subject.meshMonocytes-
dc.subject.meshNeutralization Tests-
dc.subject.meshRats-
dc.subject.meshReceptors, IgG-
dc.subject.meshRespiratory Syncytial Virus Infections-
dc.subject.meshRespiratory Syncytial Virus Vaccines-
dc.subject.meshRespiratory Syncytial Viruses-
dc.subject.meshSeverity of Illness Index-
dc.subject.meshSigmodontinae-
dc.subject.meshVaccination-
dc.subject.meshVero Cells-
dc.subject.meshViral Envelope Proteins-
dc.subject.meshViral Fusion Proteins-
dc.titleIn Vitro Enhancement of Respiratory Syncytial Virus Infection by Maternal Antibodies Does Not Explain Disease Severity in Infants.en
dc.typeArticleen
dc.identifier.journalJ Virol 2017, 91(21). pii: e00851-17en

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