Hypergammaglobulinemia and Impaired Transplacental Transfer of Respiratory Syncytial Virus Antibody in Papua New Guinea

Authors

Jessica E. Atwell, From the Department of International, Center for Immunization Research, Health Johns Hopkins School of Public Health, Baltimore, Maryland.
Bhagvanji Thumar, From the Department of International, Center for Immunization Research, Health Johns Hopkins School of Public Health, Baltimore, Maryland.
Maria A. Formica, Rochester Regional HealthFollow
Leanne J. Robinson, Rochester Regional Health
Edward E. Walsh, Rochester Regional HealthFollow
Christopher L. King, Center for Global Health and Disease, Veterans Affairs Medical Center, Case Western Reserve University, Cleveland, Ohio.
Ruth A. Karron, From the Department of International, Center for Immunization Research, Health Johns Hopkins School of Public Health, Baltimore, Maryland.

Department

Medicine

Document Type

Article

Publication Title

The Pediatric Infectious Disease Journal

Abstract

BACKGROUND: Passively-acquired respiratory syncytial virus (RSV) neutralizing antibody (Ab) can protect against RSV-associated lower respiratory tract illness. Maternal RSV immunization is, therefore, an attractive strategy for protection of very young infants. Vaccines for this purpose are currently being evaluated in clinical trials, but conditions such as preterm birth, placental malaria, maternal hypergammaglobulinemia and HIV infection might threaten this strategy. Each has been shown to impair transplacental Ab transfer for a variety of pathogens, but RSV-specific data are limited. Work in The Gambia demonstrated that placental malaria impaired transplacental transfer of RSV Ab, but a subsequent study in malaria-endemic Papua New Guinea (PNG) indicated that such associations may have been confounded by hypergammaglobulinemia (IgG > 1700 mg/dL). METHODS: Here we confirm and extend those findings by measuring RSV neutralizing Ab and maternal IgG in sera from a larger cohort of 325 mother/infant pairs in PNG, and demonstrate the applicability of a high-throughput assay for assessment of neutralizing Ab. RESULTS: One-third of mother-infant pairs demonstrated impaired RSV Ab transfer. Infants of hypergammaglobulinemic women were more likely to have both impaired transfer [cord-to-maternal titer ratio < 1.0, adjusted odds ratio (OR): 3.36 (95% confidence interval: 1.81-6.30)] and the lowest RSV cord titers [adjusted OR: 5.09 (95% confidence interval: 1.95-13.32, P < 0.001)], but neither outcome was associated with placental malaria. CONCLUSIONS: Once maternal RSV vaccines become available, successful implementation will require clear understanding and mitigation of factors that can impair passive protection, necessitating epidemiologic studies of such relationships ahead of vaccine availability. This study underscores the need to focus on hypergammaglobulinemia as a condition of importance.

First Page

e199

Last Page

e202

DOI

10.1097/INF.0000000000002364

Volume

38

Issue

9

Publication Date

9-1-2019

Medical Subject Headings

Adolescent; Adult; Antibodies, Neutralizing (blood); Antibodies, Viral (blood); Cohort Studies; Female; High-Throughput Screening Assays; Humans; Hypergammaglobulinemia (complications); Immunity, Maternally-Acquired; Immunization; Immunoglobulin G (blood); Infant; Papua New Guinea; Placenta (immunology); Pregnancy; Randomized Controlled Trials as Topic; Respiratory Syncytial Virus Infections (immunology, prevention & control); Respiratory Syncytial Virus, Human; Risk Factors; Young Adult

PubMed ID

31408055

Recommended Citation

Atwell, J. E., Thumar, B., Formica, M. A., Robinson, L. J., Walsh, E. E., King, C. L., & Karron, R. A. (2019). Hypergammaglobulinemia and Impaired Transplacental Transfer of Respiratory Syncytial Virus Antibody in Papua New Guinea. The Pediatric Infectious Disease Journal, 38 (9), e199-e202. https://doi.org/10.1097/INF.0000000000002364