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. 2019 Jan 1;219(1):59-67.
doi: 10.1093/infdis/jiy477.

Breast Milk Prefusion F Immunoglobulin G as a Correlate of Protection Against Respiratory Syncytial Virus Acute Respiratory Illness

Natalie I Mazur  1   2   3 , Nicole M Horsley  2 , Janet A Englund  4 , Maaike Nederend  3 , Amalia Magaret  5   6 , Azad Kumar  7 , Shamir R Jacobino  3 , Cornelis A M de Haan  8 , Subarna K Khatry  9 , Steven C LeClerq  10 , Mark C Steinhoff  11 , James M Tielsch  12 , Joanne Katz  10 , Barney S Graham  7 , Louis J Bont  1   13 , Jeanette H W Leusen  3 , Helen Y Chu  2
Affiliations

Breast Milk Prefusion F Immunoglobulin G as a Correlate of Protection Against Respiratory Syncytial Virus Acute Respiratory Illness

Natalie I Mazur et al. J Infect Dis. .

Abstract

Background: Transplacental respiratory syncytial virus (RSV) antibody transfer has been characterized, but little is known about the protective effect of breast milk RSV-specific antibodies. Serum antibodies against the prefusion RSV fusion protein (pre-F) exhibit high neutralizing activity. We investigate protection of breast milk pre-F antibodies against RSV acute respiratory infection (ARI).

Methods: Breast milk at 1, 3, and 6 months postpartum and midnasal swabs during infant illness episodes were collected in mother-infant pairs in Nepal. One hundred seventy-four infants with and without RSV ARI were matched 1:1 by risk factors for RSV ARI. Pre-F immunoglobulin A (IgA) and immunoglobulin G (IgG) antibody levels were measured in breast milk.

Results: The median breast milk pre-F IgG antibody concentration before illness was lower in mothers of infants with RSV ARI (1.4 [interquartile range {IQR}, 1.1-1.6] log10 ng/mL) than without RSV ARI (1.5 [IQR, 1.3-1.8] log10 ng/mL) (P = .001). There was no difference in median maternal pre-F IgA antibody concentrations in cases vs controls (1.7 [IQR, 0.0-2.2] log10 ng/mL vs 1.7 [IQR, 1.2-2.2] log10 ng/mL, respectively; P = .58).

Conclusions: Low breast milk pre-F IgG antibodies before RSV ARI support a potential role for pre-F IgG as a correlate of protection against RSV ARI. Induction of breast milk pre-F IgG may be a mechanism of protection for maternal RSV vaccines.

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Figures

Figure 1.
Figure 1.
Prefusion F (pre-F) antibody titers prior to time of infection in cases (respiratory syncytial virus positive [RSV+]) and matched controls (respiratory syncytial virus negative [RSV–]). Mann–Whitney test was performed to compare medians of cases and controls. Pre-F antibody titer was compared for measurement prior to infection. For healthy controls, antibody measurement at time of infection for age-matched cases was used. Ratio of pre-F immunoglobulin A (IgA) to total IgA (TIgA) was multiplied by 1 × 106 to ensure values on the y-axis were >0. Ratio of pre-F immunoglobulin G (IgG) and total IgG (TIgG) was multiplied by 1 × 104 for the same reason. A, Log10 pre-F IgG. B, Log10 pre-F IgA. C, Log10 pre-F IgG divided by log10 TIgG. D, Log10 pre-F IgA divided by log10 TIgA.
Figure 2.
Figure 2.
Mixed-model analysis of prefusion F (pre-F) antibody in cases and controls over time. A linear mixed-model analysis was used to examine the effect of respiratory syncytial virus (RSV) on pre-F antibodies at different time points. A, Log10 pre-F immunoglobulin G (IgG) antibody concentration at 1, 3, and 6 months postpartum for cases (RSV positive [RSV+], dark blue) and controls (RSV negative [RSV–], light blue), with medians indicated in black. B, Linear mixed-model analysis for log10 pre-F IgG in cases and controls. Solid line is the mean, and dashed line indicates the 95% confidence interval (CI). C, Log10 pre-F immunoglobulin A (IgA) antibody concentration at 1, 3, and 6 months postpartum for cases and controls, with medians in black. D, Linear mixed-model analysis for log10 pre-F IgA in cases and controls. Solid line is the mean, and dashed line indicates the 95% CI.
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