Saelens, Xavier

Schepens, Bert

English

Bert Schepens

Xavier Saelens

Directory of Open Access Journals

EBioMedicine

IgG3 Snitcher of RSV Infections in the Very Young

Ghent University Academic Bibliography

EBioMedicine 16 (2017) 10–11Contents lists available at ScienceDirectEBioMedicinej ourna l homepage: www.eb iomed ic ine.comCommentaryIgG3 Snitcher of RSV Infections in the Very YoungBert Schepens, Xavier Saelens ⁎VIB Center for Medical Biotechnology, 9052 Ghent, BelgiumDepartment of Biomedical Molecular Biology, Ghent University, 9052 Ghent, BelgiumDOI of original article: http://dx.doi.org/10.1016/j.ebi⁎ Corresponding author.E-mail address: xavier.saelens@vib-ugent.be (X. Saelehttp://dx.doi.org/10.1016/j.ebiom.2017.01.0392352-3964/© 2017 The Author(s). Published by Elsevier Ba r t i c l e i n f oArticle history:Received 27 January 2017Accepted 27 January 2017Available online 30 January 2017Theirmost remarkableﬁnding is the ability of very young infants (youn-ger than 4 months), to mount a strong IgG3 response upon RSV infec-tion even in the presence of high levels of maternal RSV-neutralizingantibodies. In contrast, a rise in RSV glycoprotein-speciﬁc serum IgG1and IgG2, and RSV-neutralizing antibodies following RSV infection wasonly observed consistently in infants older than 7months, i.e.whenma-Human respiratory syncytial virus (RSV) is the most frequent causeof lower respiratory tract infections in infants and young childrenworldwide and also an important pathogen in elderly. Millions of pa-tients get hospitalized and up to 200,000 children die each year due toan RSV infection (Nair et al., 2010). Despite this burden and decadesof research there is neither a prophylactic vaccine nor a speciﬁc antiviraltherapy for RSV. Amajor obstacle for the development of an RSV vaccineis the lack of a strong correlate of protection. High levels of RSV-neutral-izing antibodies have been associated with less severe disease but thisassociation is not strong and sometimes absent (Glezen et al., 1986;Nyiro et al., 2016). Moreover, vaccine trials learned that it is very hardto boost pre-existing RSV-neutralizing antibodies in children and adults.Maternal derived RSV-speciﬁc antibodies can provide some protec-tion in very young infants (Glezen et al., 1986). However, these mater-nal antibodies wane quickly after birth, which explains why 1-month-old babies are the most likely to develop severe disease upon primaryRSV infection (Hall et al., 2009). Remarkably, these primary infectionsdo not elicit immunity against reinfection with RSV (Glezen et al.,1986). This can in part be explained by the poor antibody response inyoung infants as compared to older children (Murphy et al., 1986).More recently, however, it has become clear that infants younger than3 months are quite capable of mounting signiﬁcant RSV-neutralizingantibodies upon RSV infection but that pre-existingmaternal antibodiescan blunt this (Shinoff et al., 2008). Profound understanding of antibodyresponses upon primary RSV infection in young infants is crucial for thedevelopment and implementation of active and passive anti-RSV vacci-nation strategies in this age group.In this issue of EBioMedicine, researchers from the pharmaceuticalcompany Daiichi Sankyo teamed up with several clinical departmentsin Japan to study the age-related humoral responses in patients withRSV who were medically attended (Jounai et al., 2017). Paired acuteand convalescent serum samples from 169 children (aged between 0om.2017.01.014.ns)..V. This is an open access article undand 36 months) and 23 adults (aged 24–89 years) were analyzed.ternal RSV antibodies had become limiting. Why does the IgG3 subclassstand out in the very young as a possible marker for a primary responseagainst RSV? First, RSV-speciﬁc IgG3 is virtually absent in infants youn-ger than 4 months. Due to its shorter half-life (7 days compared to21 days for the other IgG isotypes) IgG3 levels in both the mother andinfant decline much faster than IgG1 and IgG2 do (Hornsleth et al.,1985). Secondly, extensive sequence analysis of human IgG transcriptshas revealed a clear hierarchy among the IgG subclasses and the extentof afﬁnity maturation: IgG3 b IgG1 b IgG2 b IgG4 (Jackson et al., 2014).This suggests that human B cells tend to follow a programmed sequenceof class switches from IgM to IgG3 and subsequently to IgG1, IgG2 andIgG4. Recurrent infections with RSV would thus also gradually favor ac-cumulation of RSV-speciﬁc IgG1, IgG2 and IgG4 over IgG3 as an individ-ual grows up.In the study population of Jounai et al. RSV-speciﬁc IgG1 and IgG2 re-sponses upon medical attended RSV infection were undetectable in in-fants younger than 4 months and could only be observed in about onethird of the infants aged between 4 and 7 months (Jounai et al., 2017).In accordance with other reports, the infections did not result in robustRSV-neutralizing antibody responses in these infants (Murphy et al.,1986). In contrast, RSV infections were associated with a more than 4-fold increase in IgG3 levels in 78.3% and 96.4% of 0–4 months old and4–7 months old infants, respectively. RSV-speciﬁc serum IgG3 re-sponses might thus serve as a biomarker for primary RSV infectionand associated immune responses. This might be useful to detect sub-clinical RSV infections in young infants with considerable levels of ma-ternal RSV antibodies, or to monitor early immune responses uponvaccination with live attenuated RSV vaccine candidates. To further ex-plore IgG3 response as a biomarker for RSV infections and associatedimmune responses, it will be important to deﬁne the duration of suchan IgG3 response, given its short half-life. In addition, it should be inves-tigated to what extent also subclinical RSV infections result in detect-able IgG3 responses. Finally, RSV IgG3 responses should also beinvestigated in infants less than 1 or 2months of age. If upon subclinicalRSV infections early and strong IgG3 responses occur in very young in-fants and remain detectable for a prolonged period, this IgG3 markholds promise as a feasible biomarker.er the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).11B. Schepens, X. Saelens / EBioMedicine 16 (2017) 10–11DisclosureThe authors declared no conﬂicts of interest.ReferencesGlezen,W.P., Taber, L.H., Frank, A.L., Kasel, J.A., 1986. Risk of primary infection and reinfec-tion with respiratory syncytial virus. Am. J. Dis. Child 140, 543–546.Hall, C.B., Weinberg, G.A., Iwane, M.K., Blumkin, A.K., Edwards, K.M., Staat, M.A., Auinger,P., Grifﬁn, M.R., Poehling, K.A., Erdman, D., Grijalva, C.G., Zhu, Y., Szilagyi, P., 2009. Theburden of respiratory syncytial virus infection in young children. N. Engl. J. Med. 360,588–598.Hornsleth, A., Bech-Thomsen, N., Friis, B., 1985. Detection by ELISA of IgG-subclass-speciﬁc antibodies in primary respiratory syncytial (RS) virus infections. J. Med.Virol. 16, 321–328.Jackson, K.J., Wang, Y., Collins, A.M., 2014. Human immunoglobulin classes and subclassesshow variability in VDJ gene mutation levels. Immunol. Cell Biol. 92, 729–733.Jounai, N., Yoshioka, M., Tozuka, M., Inoue, K., Oka, T., Takeshita, F., 2017. Age-speciﬁc pro-ﬁles of antibody responses against respiratory syncytial virus infection. EBioMedicinehttp://dx.doi.org/10.1016/j.ebiom.2017.01.014.Murphy, B.R., Alling, D.W., Snyder, M.H., Walsh, E.E., Prince, G.A., Chanock, R.M.,Hemming, V.G., Rodriguez, W.J., Kim, H.W., Graham, B.S., et al., 1986. Effect of ageand preexisting antibody on serum antibody response of infants and children tothe F and G glycoproteins during respiratory syncytial virus infection. J. Clin.Microbiol. 24, 894–898.Nair, H., Nokes, D.J., Gessner, B.D., Dherani, M., Madhi, S.A., Singleton, R.J., O'Brien, K.L.,Roca, A., Wright, P.F., Bruce, N., Chandran, A., Theodoratou, E., Sutanto, A.,Sedyaningsih, E.R., Ngama, M., Munywoki, P.K., Kartasasmita, C., Simoes, E.A.,Rudan, I., Weber, M.W., Campbell, H., 2010. Global burden of acute lower respiratoryinfections due to respiratory syncytial virus in young children: a systematic reviewand meta-analysis. Lancet 375, 1545–1555.Nyiro, J.U., Sande, C.J., Mutunga, M., Kiyuka, P.K., Munywoki, P.K., Scott, J.A., Nokes, D.J.,2016. Absence of association between cord speciﬁc antibody levels and severe respi-ratory syncytial virus (RSV) disease in early infants: a case control study from CoastalKenya. PLoS One 11, e0166706.Shinoff, J.J., O'Brien, K.L., Thumar, B., Shaw, J.B., Reid, R., Hua, W., Santosham, M., Karron,R.A., 2008. Young infants can develop protective levels of neutralizing antibodyafter infection with respiratory syncytial virus. J. Infect. Dis. 198, 1007–1015.

IgG3 snitcher of RSV infections in the very young

Schepens, BertWE10001995250691801001519119F6223658-F0ED-11E1-A9DE-61C894A0A6B4

Saelens, XavierWE108010007799960000-0002-3861-6965F48175CA-F0ED-11E1-A9DE-61C894A0A6B4

Archivsystem Ask23

Crossref

https://biblio.ugent.be/publication/8512258/file/8512262

IgG3 snitcher of RSV infections in the very young

Abstract

Similar works

Full text

Available Versions

Directory of Open Access Journals

Ghent University Academic Bibliography

Archivsystem Ask23

Crossref