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

Atwell, Jessica E. PhD, MPH*; Thumar, Bhagvanji MS*; Formica, Maria A. MS; Robinson, Leanne J. PhD, MPH†,§; Walsh, Edward E. MD; King, Christopher L. MD, PhD; Karron, Ruth A. MD*

The Pediatric Infectious Disease Journal: September 2019 - Volume 38 - Issue 9 - p e199–e202
doi: 10.1097/INF.0000000000002364
Original Studies
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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.

From the *Department of International, Center for Immunization Research, Health Johns Hopkins School of Public Health, Baltimore, Maryland

Department of Medicine, Rochester General Hospital, University of Rochester, New York, New York

Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea

§Burnet Institute, Victoria, Australia

Center for Global Health and Disease, Veterans Affairs Medical Center, Case Western Reserve University, Cleveland, Ohio.

Accepted for publication March 11, 2019.

Supported by PATH and the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (NIH) (AI AI064687 and DMID #11–0037).

J.E.A. reports grants from PATH Vaccines, during the conduct of the study; personal fees from PATH, personal fees from Gavi, and grants from Novavax Vaccines and GSK vaccines outside the submitted work. R.A.K. reports grants from PATH Vaccines, during the conduct of the study; grants from NIH outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Address for correspondence: Jessica E. Atwell, PhD, MPH, Department of International Health, Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, 624 N. Broadway, Baltimore, MD 21205. E-mail: jatwell@jhu.edu.

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