Impact of maternal SARS-CoV-2 booster vaccination on blood and breastmilk antibodies

Abstract

Maternal COVID-19 vaccination could protect infants who are ineligible for vaccine through antibody transfer during pregnancy and lactation. We measured the quantity and durability of SARS-CoV-2 antibodies in human milk and infant blood before and after maternal booster vaccination. Prospective cohort of lactating women immunized with primary and booster COVID-19 vaccines during pregnancy or lactation and their infants. Milk and blood samples from October 2021 to April 2022 were included. Anti-nucleoprotein (NP) and anti-receptor binding domain (RBD) IgG and IgA in maternal milk and maternal and infant blood were measured and compared longitudinally after maternal booster vaccine. Forty-five lactating women and their infants provided samples. 58% of women were anti-NP negative and 42% were positive on their first blood sample prior to booster vaccine. Anti-RBD IgG and IgA in milk remained significantly increased through 120-170 days after booster vaccine and did not differ by maternal NP status. Anti-RBD IgG and IgA did not increase in infant blood after maternal booster. Of infants born to women vaccinated in pregnancy, 74% still had positive serum anti-RBD IgG measured on average 5 months after delivery. Infant to maternal IgG ratio was highest for infants exposed to maternal primary vaccine during the second trimester compared to third trimester (0.85 versus 0.29; p<0.001). Maternal COVID-19 primary and booster vaccine resulted in robust and long-lasting transplacental and milk antibodies. These antibodies may provide important protection against SARS-CoV-2 during the first six months of life.

Fig 1. Consort diagram of participants from parent study included in current analysis.

Fig 2. Flow chart of anti-NP results and COVID-19 infections in samples of women included in study (N = 45).

Fig 3

A-F. SARS-CoV-2 anti-receptor binding domain (RBD) IgG and IgA geometric mean titer (GMT) in maternal and infant blood and milk before and after maternal COVID-19 booster vaccine (N = 45 pairs). The dotted lines indicate the positive cutoff titer of 900 for IgG and 300 for IgA in blood (A,B, E, F) and 4 for IgG and 8 for IgA in milk (C, D). Mixed effects models with Geisser-Greenhouse correction and Sidak’s multiple comparisons test was used to assess differences over time. Error bars indicate GMT standard deviation. Timepoint comparisons not significant unless otherwise shown; *: p<0.05; **p<0.01; ***p<0.001; **** p<0.0001. Anti-RBD IgG and IgA was significantly increased in maternal blood through 60–119 days after booster vaccine and in milk through 120–170 days after booster vaccine (A-D) regardless of maternal NP status. Anti-RBD IgG GMT in milk continued to increase between 15–35 days and 60–119 days after vaccination (C). Infants of women vaccinated during lactation showed no increase in serum anti-RBD IgG or IgA antibodies after maternal booster vaccine (E- F). Infants of women vaccinated during pregnancy showed a decrease in serum anti-RBD IgG between samples (E).

Fig 4

A, B. Correlation of human milk anti-receptor binding domain (RBD) IgG and IgA with serum IgG and IgA before and after COVID-19 booster vaccine (N = 45 paired samples). The colors represent the different time points. The dotted lines indicate the positive cutoff titer for IgG (900 for serum and 4 for milk) and IgA (300 for serum and 8 for milk). Milk IgG correlated with IgG in serum before and at 15–35 days and 60–119 days after booster vaccine (A). Milk IgA correlated with IgA in serum at 14–35 days after booster vaccine (B). Correlations were analyzed using Pearson correlation coefficient.

Fig 5. Flow chart of anti-NP results and COVID-19 infections in samples from children included in study.

Fig 6. Comparison of infant to maternal anti-receptor binding domain (RBD) IgG among mother-infant pairs who are both negative for anti-NP in serum obtained before COVID-19 booster vaccine by trimester of vaccination with primary COVID-19 vaccine series (N = 15).