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

Abstract

BackgroundTransplacental 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).MethodsBreast 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.ResultsThe 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).ConclusionsLow 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.

Global Perspectives on Immunization During Pregnancy and Priorities for Future Research and Development: An International Consensus Statement

“…A study from South Africa found that breastmilk sIgA against GBS was associated with lower risk for GBS LOD in young infants (229). In a study from Nepal, breastmilk RSV IgG levels, but not IgA levels, were lower in mothers of infants with RSV acute respiratory infection (230). While these studies report potential association between breastfeeding and reduction in disease risk, the casual relationship has not been confirmed.…”

Survival of Recombinant Monoclonal Antibodies (IgG, IgA and sIgA) Versus Naturally-Occurring Antibodies (IgG and sIgA/IgA) in an Ex Vivo Infant Digestion Model

“…The palivizumab (IgG, IgA, and sIgA) and naturally-occurring RSV F protein-specific (IgG and sIgA/IgA) concentrations in gastric and intestinal samples and ex-vivo-incubated samples were quantified by ELISA as described by Mazur et al [14] with modifications. Nunc MaxiSorp 96-well plates (Thermo Scientific, Waltham, MA, USA) were coated at 4 • C overnight with 100 µL of 100 ng/mL human RSV pre-fusion F protein (Sino Biological, Wayne, PA, USA).…”

COVID-19 and human milk: SARS-CoV-2, antibodies, and neutralizing capacity

“…[16][17][18] Many of the health-promoting effects of breastfeeding are due to the provision of passive immunity via immunoglobulins and other bioactive factors (e.g., lactoferrin), and previous studies have shown that milk-borne antibodies are produced in response to viral infection. [19][20][21][22] However, few studies have examined the presence of antibodies to SARS-CoV-2 in human milk. 23,24 In one recent study, milk from 12 of 15 women previously infected with SARS-CoV-2 contained IgA that was reactive to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein.…”