Transplacental transfer of Lassa IgG antibodies in pregnant women in Southern Nigeria: A prospective hospital-based cohort study

Abstract

Background: Evidence from previous studies suggest that Lassa fever, a viral haemorrhagic fever endemic to West Africa has high case fatalities, particularly in pregnancy. While there have been remarkable innovations in vaccine development, with some Lassa vaccines undergoing early clinical trials. An understanding of Lassa antibody kinetics and immune responses will support vaccine design and development. However, there is currently no evidence on the antibody kinetics of Lassa (LASV) in pregnancy. Our study sought to estimate the efficiency of transplacental transfer of LASV IgG antibodies from the mother to the child.

Methodology/principal findings: The study made use of data from a prospective hospital-based cohort of pregnant women enrolled at the antenatal clinic and followed up at delivery between February and December 2019. Blood samples from mother-child pairs were evaluated for antibodies against Lassa virus. The study demonstrates a transplacental transfer of LASV IgG of 75.3% [60.0-94.0%], with a significant positive correlation between maternal and cord concentrations and a good level of agreement. The study also suggests that transfer may be more variable in women with 'de novo' antibodies compared to those with pre-existing antibodies.

Conclusions/significance: The study shows that maternal antibody levels play an important role in determining transfer efficiency of Lassa antibodies to the new-born; and while the evidence is preliminary, the study also suggests that transfer efficiency may be less stable in acute or recent infection, as such timing of vaccination before pregnancy, that is in women of childbearing age may be more appropriate for protection of both pregnant women and their neonates.

Fig 1. Correlation between maternal and cord Lassa and TT IgG antibodies assessed by Spearman’s correlation (r).

Note: IV- index value; mCMR- median cord maternal ratio; black dotted horizontal line is line of seropositivity (LASV = 1.1, TT = 0.1IU/mL); blue line is the regression line; grey shaded are the 95% confidence interval fitted to the regression line.

Fig 2. Correlation plots between cord maternal ratio and maternal LASV and TT IgG concentrations assessed by Spearman’s correlation (r).

Note: mCMR- median cord maternal ratio; IV- index value, an arbitrary antibody concentration unit based on manufacturer’s guide; the dotted black horizontal line is the line of efficient transfer (CMR = 1); Log- natural logarithm; blue line is the regression line; grey shaded are the 95% confidence interval fitted to the regression line.

Fig 3. Correlation plots for LASV IgG assessed by Spearman’s correlation (r) using linear regression.

Note: +/+ indicates seropositive from baseline. -/+ indicates seroconversion. The dotted black horizontal line indicates the line of efficient transfer (CMR = 1); IV- index value, an arbitrary antibody concentration unit based on manufacturer’s guide; mCMR- median cord maternal ratio; black and red lines are regression lines with the corresponding 95% confidence interval fitted to the regression line.

Fig 4. Bland-Altman plot showing agreement between maternal and cord Lassa and TT IgG antibodies.

Note: IV- index value; dotted black lines indicate limits of agreement (± 2sddiff); dotted red line indicates mean difference between maternal and cord concentrations; mdiff- mean difference; sddiff- standard deviation of differences.