Maternal Epstein-Barr Virus-Specific Antibodies and Risk of Infection in Ugandan Infants

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2020 Oct 23

PMID 33095855

Citations 3

Authors

Rana Minab

Wei Bu

Hanh Nguyen

Abigail Wall

Anton M Sholukh

Meei-Li Huang

Michael Ortego

Elizabeth M Krantz

Michael Irvine

Corey Casper

Jackson Orem

Andrew T McGuire

Jeffrey I Cohen

Soren Gantt

Affiliations

Soon will be listed here.

Abstract

Background: Epstein-Barr virus (EBV) infection is a major cause of malignancy worldwide. Maternal antibody is thought to prevent EBV infection because it is uncommon in early infancy. Maternal HIV infection is associated with an increased incidence of EBV infection in exposed infants, which we hypothesized results from impaired transfer of EBV-neutralizing maternal antibodies.

Methods: Among Ugandan infants followed for EBV acquisition from birth, we measured antibody binding to EBV glycoproteins (gp350, gH/gL) involved in B-cell and epithelial-cell entry, as well as viral neutralization and antibody-dependent cellular cytotoxicity (ADCC) activity in plasma samples prior to infection. These serologic data were analyzed for differences between HIV-exposed uninfected (HEU) and HIV-unexposed (HUU) infants, and for associations with incident infant EBV infection.

Results: HEU infants had significantly higher titers than HUU infants for all EBV-binding and neutralizing antibodies measured (P < .01) but not ADCC activity, which was similar between groups. No antibody measure was associated with a decreased risk of EBV acquisition in the cohort.

Conclusions: Our findings indicate that in this cohort maternal antibody did not protect infants against EBV infection through viral neutralization. The identification of protective nonneutralizing antibody functions would be invaluable for the development of an EBV vaccine.

Citing Articles

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References

Jones C, Naidoo S, De Beer C, Esser M, Kampmann B, Hesseling A . Maternal HIV infection and antibody responses against vaccine-preventable diseases in uninfected infants. JAMA. 2011; 305(6):576-84. DOI: 10.1001/jama.2011.100. View

Tsai M, Raykova A, Klinke O, Bernhardt K, Gartner K, Leung C . Spontaneous lytic replication and epitheliotropism define an Epstein-Barr virus strain found in carcinomas. Cell Rep. 2013; 5(2):458-70. DOI: 10.1016/j.celrep.2013.09.012. View

Kaye S, Miles D, Antoine P, Burny W, Ojuola B, Kaye P . Virological and immunological correlates of mother-to-child transmission of cytomegalovirus in The Gambia. J Infect Dis. 2008; 197(9):1307-14. DOI: 10.1086/586715. View

Hjalgrim H, Askling J, Rostgaard K, Hamilton-Dutoit S, Frisch M, Zhang J . Characteristics of Hodgkin's lymphoma after infectious mononucleosis. N Engl J Med. 2003; 349(14):1324-32. DOI: 10.1056/NEJMoa023141. View

Bu W, Joyce M, Nguyen H, Banh D, Aguilar F, Tariq Z . Immunization with Components of the Viral Fusion Apparatus Elicits Antibodies That Neutralize Epstein-Barr Virus in B Cells and Epithelial Cells. Immunity. 2019; 50(5):1305-1316.e6. PMC: 6660903. DOI: 10.1016/j.immuni.2019.03.010. View

Levin L, Munger K, OReilly E, Falk K, Ascherio A . Primary infection with the Epstein-Barr virus and risk of multiple sclerosis. Ann Neurol. 2010; 67(6):824-30. PMC: 3089959. DOI: 10.1002/ana.21978. View

Snijder J, Ortego M, Weidle C, Stuart A, Gray M, McElrath M . An Antibody Targeting the Fusion Machinery Neutralizes Dual-Tropic Infection and Defines a Site of Vulnerability on Epstein-Barr Virus. Immunity. 2018; 48(4):799-811.e9. PMC: 5909843. DOI: 10.1016/j.immuni.2018.03.026. View

Martinez D, Fong Y, Li S, Yang F, Jennewein M, Weiner J . Fc Characteristics Mediate Selective Placental Transfer of IgG in HIV-Infected Women. Cell. 2019; 178(1):190-201.e11. PMC: 6727200. DOI: 10.1016/j.cell.2019.05.046. View

Odumade O, Hogquist K, Balfour Jr H . Progress and problems in understanding and managing primary Epstein-Barr virus infections. Clin Microbiol Rev. 2011; 24(1):193-209. PMC: 3021204. DOI: 10.1128/CMR.00044-10. View

10.

Piriou E, Asito A, Sumba P, Fiore N, Middeldorp J, Moormann A . Early age at time of primary Epstein-Barr virus infection results in poorly controlled viral infection in infants from Western Kenya: clues to the etiology of endemic Burkitt lymphoma. J Infect Dis. 2012; 205(6):906-13. PMC: 3282570. DOI: 10.1093/infdis/jir872. View

11.

Biggar R, Henle W, Fleisher G, Bocker J, Lennette E, Henle G . Primary Epstein-Barr virus infections in African infants. I. Decline of maternal antibodies and time of infection. Int J Cancer. 1978; 22(3):239-43. DOI: 10.1002/ijc.2910220304. View

12.

Bu W, Hayes G, Liu H, Gemmell L, Schmeling D, Radecki P . Kinetics of Epstein-Barr Virus (EBV) Neutralizing and Virus-Specific Antibodies after Primary Infection with EBV. Clin Vaccine Immunol. 2016; 23(4):363-9. PMC: 4820504. DOI: 10.1128/CVI.00674-15. View

13.

Chan K, Tam J, Peiris J, Seto W, Ng M . Epstein-Barr virus (EBV) infection in infancy. J Clin Virol. 2001; 21(1):57-62. DOI: 10.1016/s1386-6532(01)00149-4. View

14.

Day N, Geser A, Lavoue M, Ho J, SIMONS M, SOHIER R . Sero-epidemiology of the Epstein-Barr virus: preliminary analysis of an international study - a review. IARC Sci Publ (1971). 1975; (11 Pt 2):3-16. View

15.

Kim J, Excler J, Michael N . Lessons from the RV144 Thai phase III HIV-1 vaccine trial and the search for correlates of protection. Annu Rev Med. 2014; 66:423-37. DOI: 10.1146/annurev-med-052912-123749. View

16.

Pou C, Nkulikiyimfura D, Henckel E, Olin A, Lakshmikanth T, Mikes J . The repertoire of maternal anti-viral antibodies in human newborns. Nat Med. 2019; 25(4):591-596. DOI: 10.1038/s41591-019-0392-8. View

17.

Hsieh F, Lavori P . Sample-size calculations for the Cox proportional hazards regression model with nonbinary covariates. Control Clin Trials. 2001; 21(6):552-60. DOI: 10.1016/s0197-2456(00)00104-5. View

18.

Jennewein M, Goldfarb I, Dolatshahi S, Cosgrove C, Noelette F, Krykbaeva M . Fc Glycan-Mediated Regulation of Placental Antibody Transfer. Cell. 2019; 178(1):202-215.e14. PMC: 6741440. DOI: 10.1016/j.cell.2019.05.044. View

19.

Bilger A, Plowshay J, Ma S, Nawandar D, Barlow E, Romero-Masters J . Leflunomide/teriflunomide inhibit Epstein-Barr virus (EBV)- induced lymphoproliferative disease and lytic viral replication. Oncotarget. 2017; 8(27):44266-44280. PMC: 5546479. DOI: 10.18632/oncotarget.17863. View

20.

Binyamin L, Alpaugh R, Hughes T, Lutz C, Campbell K, Weiner L . Blocking NK cell inhibitory self-recognition promotes antibody-dependent cellular cytotoxicity in a model of anti-lymphoma therapy. J Immunol. 2008; 180(9):6392-401. PMC: 2810560. DOI: 10.4049/jimmunol.180.9.6392. View