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

Natalie I. Mazur, Nicole M. Horsley, Janet A. Englund, Maaike Nederend, Amalia Magaret, Azad Kumar, Shamir R. Jacobino, Cornelis A.M. de Haan, Subarna K. Khatry, Steven C. LeClerq, Mark C. Steinhoff, James M. Tielsch, Joanne Katz, Barney S. Graham, Louis J. Bont, Jeanette H.W. Leusen, Helen Y. Chu

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)59-67
Number of pages9
JournalThe Journal of infectious diseases
Volume219
Issue number1
DOIs
StatePublished - Jan 1 2019

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Respiratory Syncytial Viruses
Human Milk
Immunoglobulin G
Respiratory Tract Infections
Antibodies
Mothers
Immunoglobulin A
Respiratory Syncytial Virus Vaccines
Viral Fusion Proteins
Nepal
Postpartum Period

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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Breast Milk Prefusion F Immunoglobulin G as a Correlate of Protection Against Respiratory Syncytial Virus Acute Respiratory Illness. / Mazur, Natalie I.; Horsley, Nicole M.; Englund, Janet A.; Nederend, Maaike; Magaret, Amalia; Kumar, Azad; Jacobino, Shamir R.; de Haan, Cornelis A.M.; Khatry, Subarna K.; LeClerq, Steven C.; Steinhoff, Mark C.; Tielsch, James M.; Katz, Joanne; Graham, Barney S.; Bont, Louis J.; Leusen, Jeanette H.W.; Chu, Helen Y.

In: The Journal of infectious diseases, Vol. 219, No. 1, 01.01.2019, p. 59-67.

Research output: Contribution to journalArticle

Mazur, NI, Horsley, NM, Englund, JA, Nederend, M, Magaret, A, Kumar, A, Jacobino, SR, de Haan, CAM, Khatry, SK, LeClerq, SC, Steinhoff, MC, Tielsch, JM, Katz, J, Graham, BS, Bont, LJ, Leusen, JHW & Chu, HY 2019, 'Breast Milk Prefusion F Immunoglobulin G as a Correlate of Protection Against Respiratory Syncytial Virus Acute Respiratory Illness' The Journal of infectious diseases, vol. 219, no. 1, pp. 59-67. https://doi.org/10.1093/infdis/jiy477
Mazur, Natalie I. ; Horsley, Nicole M. ; Englund, Janet A. ; Nederend, Maaike ; Magaret, Amalia ; Kumar, Azad ; Jacobino, Shamir R. ; de Haan, Cornelis A.M. ; Khatry, Subarna K. ; LeClerq, Steven C. ; Steinhoff, Mark C. ; Tielsch, James M. ; Katz, Joanne ; Graham, Barney S. ; Bont, Louis J. ; Leusen, Jeanette H.W. ; Chu, Helen Y. / Breast Milk Prefusion F Immunoglobulin G as a Correlate of Protection Against Respiratory Syncytial Virus Acute Respiratory Illness. In: The Journal of infectious diseases. 2019 ; Vol. 219, No. 1. pp. 59-67.
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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.",
author = "Mazur, {Natalie I.} and Horsley, {Nicole M.} and Englund, {Janet A.} and Maaike Nederend and Amalia Magaret and Azad Kumar and Jacobino, {Shamir R.} and {de Haan}, {Cornelis A.M.} and Khatry, {Subarna K.} and LeClerq, {Steven C.} and Steinhoff, {Mark C.} and Tielsch, {James M.} and Joanne Katz and Graham, {Barney S.} and Bont, {Louis J.} and Leusen, {Jeanette H.W.} and Chu, {Helen Y.}",
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T1 - Breast Milk Prefusion F Immunoglobulin G as a Correlate of Protection Against Respiratory Syncytial Virus Acute Respiratory Illness

AU - Mazur, Natalie I.

AU - Horsley, Nicole M.

AU - Englund, Janet A.

AU - Nederend, Maaike

AU - Magaret, Amalia

AU - Kumar, Azad

AU - Jacobino, Shamir R.

AU - de Haan, Cornelis A.M.

AU - Khatry, Subarna K.

AU - LeClerq, Steven C.

AU - Steinhoff, Mark C.

AU - Tielsch, James M.

AU - Katz, Joanne

AU - Graham, Barney S.

AU - Bont, Louis J.

AU - Leusen, Jeanette H.W.

AU - Chu, Helen Y.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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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