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. 2016 Feb 1;213(3):423-31.
doi: 10.1093/infdis/jiv401. Epub 2015 Aug 3.

Impact of Placental Malaria and Hypergammaglobulinemia on Transplacental Transfer of Respiratory Syncytial Virus Antibody in Papua New Guinea

Jessica E Atwell  1 , Bhagvanji Thumar  1 , Leanne J Robinson  2 , Roselyn Tobby  3 , Phantica Yambo  3 , Maria Ome-Kaius  3 , Peter M Siba  4 , Holger W Unger  5 , Stephen J Rogerson  5 , Christopher L King  6 , Ruth A Karron  1
Affiliations

Impact of Placental Malaria and Hypergammaglobulinemia on Transplacental Transfer of Respiratory Syncytial Virus Antibody in Papua New Guinea

Jessica E Atwell et al. J Infect Dis. .

Abstract

Background: Passively acquired respiratory syncytial virus (RSV) neutralizing antibody protects against RSV-associated lower respiratory infections, but placental malaria (PM) and maternal hypergammaglobulinemia might interfere with transplacental immunoglobulin transport.

Methods: We measured RSV plaque-reduction neutralization (PRN) antibody in 300 full-term maternal/cord serum pairs in 2 cohorts in malaria-endemic Papua New Guinea: Alexishafen (2005-2008) and the Fetal Immunity Study (FIS) (2011-2013). We defined impaired transport as a cord-to-maternal titer ratio <1.0 and a protective RSV PRN titer (PRNT) ≥1:200.

Results: PM and hypergammaglobulinemia occurred in 60% and 54% of Alexishafen mothers versus 8% and 9% of FIS mothers, respectively. 34% of Alexishafen and 32% of FIS pairs demonstrated impaired transport. Multivariate modeling revealed significant associations between increasing maternal IgG (log2) and impaired transport (adjusted OR, Alexishafen: 2.68 [1.17-6.14], FIS: 6.94 [1.94-24.8]) but no association with PM. 34% of Alexishafen and 31% of FIS cord PRNTs were <1:200.

Conclusions: Impaired RSV antibody transport was observed in approximately one-third of maternal/cord pairs. Hypergammaglobulinemia, but not PM, was associated with impaired transport, particularly among women with low RSV PRNT. Detection of RSV PRNT <1:200 in one-third of cord sera confirms the need to increase levels of RSV neutralizing antibody in pregnant women through maternal immunization.

Keywords: RSV; hypergammaglobulinemia; maternal immunization; placental malaria; transplacental transfer of antibody.

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Figures

Figure 1.
Figure 1.
Relationship of maternal respiratory syncytial virus (RSV) plaque-reduction neutralizing titer (PRNT) to cord RSV PRNT in the presence and absence of placental malaria (PM). PRNTs are expressed as reciprocal log2. In each graph, the solid line represents a cord-to-maternal titer ratio of 1.0. A, Alexishafen cohort, all pairs. B, Alexishafen cohort, PM-positive pairs. C, Alexishafen cohort, PM-negative pairs. D, FIS cohort, all pairs. E, FIS cohort, PM-positive pairs. F, FIS cohort, PM-negative pairs. Abbreviation: FIS, Fetal Immunity Study.
Figure 2.
Figure 2.
Distributions of maternal IgG in each study cohort. Alexishafen cohort (A); FIS cohort (B). IgG levels are expressed as mg/dL. The dashed line represents the threshold for hypergammaglobulinemia (1700 mg/dL). Abbreviations: FIS, Fetal Immunity Study; IgG, immunoglobulin G.
Figure 3.
Figure 3.
A, The relationship between placental malaria (PM) and hypergammaglobulinemia. Left circle, proportion of mothers with PM by histology; right circle, proportion of mothers with hypergammaglobulinemia; shaded middle area, proportion of mothers with both PM and hypergammaglobulinemia. B, The relationship between cord-to-maternal titer ratios (CMTRs) and cord plaque-reduction neutralization titers (PRNTs). Left circle, proportion of maternal/cord pairs exhibiting CMTR <1.0; right circle, proportion of cord specimens with PRNT <1:200, shaded middle area, proportion of cord specimens where CMTR was <1.0 and PRNT was <1:200. Abbreviation: FIS, Fetal Immunity Study.
Figure 4.
Figure 4.
Reverse cumulative distribution of cord respiratory syncytial virus (RSV) plaque-reduction neutralization titers (PRNTs) by cohort. The solid line represents the Alexishafen cohort and the dotted line represents the FIS cohort. The vertical solid line indicates a cord PRNT of 1:200. Abbreviation: FIS, Fetal Immunity Study.
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