Maternal transfer of IgA and IgG SARS-CoV-2 specific antibodies transplacentally and via breast milk feeding

Abstract

Background: Although there have been many studies on antibody responses to SARS-CoV-2 in breast milk, very few have looked at the fate of these in the infant, and whether they are delivered to immunologically relevant sites in infants.

Methods: Mother/infant pairs (mothers who breast milk fed and who were SARS-CoV-2 vaccinated before or after delivery) were recruited for this cross-sectional study. Mother blood, mother breast milk, infant blood, infant nasal specimen, and infant stool was tested for IgA and IgG antibodies against SARS-CoV-2 spike trimer.

Results: Thirty-one mother/infant pairs were recruited. Breast milk fed infants acquired systemic anti-spike IgG antibodies only if their mothers were vaccinated antepartum (100% Antepartum; 0% Postpartum; P<0.0001). Breast milk fed infants acquired mucosal anti-spike IgG antibodies (in the nose) only if their mothers were vaccinated antepartum (89% Antepartum; 0% Postpartum; P<0.0001). None of the infants in either group had anti-spike IgA in the blood. Surprisingly, 33% of the infants whose mothers were vaccinated antepartum had high titer anti-spike IgA in the nose (33% Antepartum; 0% Postpartum; P = 0.03). Half-life of maternally transferred plasma IgG antibodies in the Antepartum infant cohort was ~70 days.

Conclusion: Vaccination antepartum followed by breast milk feeding appears to be the best way to provide systemic and local anti-SARS-CoV-2 antibodies for infants. The presence of high titer SARS-CoV-2-specific IgA in the nose of infants points to the potential importance of breast milk feeding early in life for maternal transfer of mucosal IgA antibodies. Expectant mothers should consider becoming vaccinated antepartum and consider breast milk feeding for optimal transfer of systemic and mucosal antibodies to their infants.

Fig 1. SARS-CoV-2 spike binding titers in vaccinated mothers and infants.

A) Log anti-spike IgG binding titer in mother plasma, breast milk, infant plasma, infant nose, and infant stool. Samples below the limited of detection were given an arbitrary value of 0.5. Horizontal red lines represent median values. B) Log anti-spike IgA binding titer in mother plasma, breast milk, infant plasma, infant nose, infant stool. Samples below the limited of detection were given an arbitrary value of 0.5. Horizontal red lines represent medians values, and dotted lines the limit of detection. All ELISAs were designed to detect SARS-CoV-2 spike trimer, samples run in duplicate, and all results reported as endpoint titers. Nasal anti-spike IgG and IgA endpoint titers are reported here as direct results (without providing a ratio with total nasal IgG or IgA). Differences between groups were tested by the 2-tailed Fisher’s exact test, with a P ≤0.05 being considered significant. * = P ≤ 0.05; ** = P ≤ 0.01; *** = P ≤ 0.001; **** = P ≤ 0.0001.

Fig 2. Mucosal humoral immunity in infants.

A) IgG and IgA binding titer in infant nose. Horizontal red lines represent median values. B) IgA/IgG endpoint titer in infant nose. Horizontal red lines represent median values. C) Nasal endpoint titers expressed as ratio between anti-spike endpoint titer/Total class endpoint titer. Differences between groups were tested by the 2-tailed Mann Whitney test, with a P ≤0.05 being considered significant. * = P ≤ 0.05; ** = P ≤ 0.01; *** = P ≤ 0.001; **** = P ≤ 0.0001.

Fig 3. Infant antibodies to SARS-CoV-2 spike antigen over time.

A) Infant plasma and nasal anti-spike IgG log transformed and plotted (Y-axis) vs sampling day (X-axis). Samples below the limit of detection were given an arbitrary value of 15. B) Infant nasal anti-spike IgA log transformed and plotted (Y-axis) vs sampling day (X-axis). Samples testing negative were given an arbitrary value of 15. Nasal anti-spike IgG and IgA endpoint titers are reported here as direct results (without providing a ratio with total nasal IgG or IgA).

Fig 4. Half-life of maternal IgG in infants and correlation between SARS-CoV-2 spike antibodies nasal and plasma anti-spike IgG.

A) Cross-sectional anti-spike IgG from antepartum infant plasma and nasal samples. Using linear regression, cross-sectional plasma IgG t1/2 = 56.9 days; cross-sectional nasal IgG t1/2 = 83.6 days. B) Correlation between plasma and nasal anti-spike IgG endpoint titers. P<0.0001; R² = 0.68. Nasal anti-spike endpoint titers provided as a ratio between nasal IgG endpoint titer/total nasal IgG endpoint titer.