Coronavirus Disease 2019 Vaccine Booster Effects Are Seen in Human Milk Antibody Response

Abstract

Infants remain at high risk for severe coronavirus disease 2019 (COVID-19). Human milk contains high levels of protective SARS CoV-2 specific antibodies post-infection and primary vaccine series, but levels decline over time. We hypothesized that the COVID-19 booster vaccine augment antibody production and the protection afforded to human milk-fed infants. We prospectively enrolled pregnant or lactating mothers planning to receive COVID-19 vaccination. We measured human milk IgG, IgA, and IgM antibodies targeting the SARS CoV-2 receptor binding domain within the spike protein and human milk neutralization activity against SARS CoV-2 in 10 lactating mothers from pre-COVID-19 primary series vaccine to post-booster dose. Human milk SARS CoV-2 specific IgG increased significantly from pre- to post-booster levels (median OD 0.33 vs. 2.02, P = 0.002). The IgG levels post-booster were even higher than the peak level after the primary series (2.02 vs. 0.95, P = 0.03). The increase in SARS CoV-2 specific IgA levels was not significant (0.10 vs. 0.33, P = 0.23). There was a strong correlation between paired maternal blood and milk IgG and IgA levels (IgG rho 0.52, P < 0.001, IgA rho 0.31, P = 0.05). Post-booster neutralizing activity was elevated compared to pre-booster levels (66% vs. 12% inhibition, P = 0.002). COVID-19 vaccine booster elicits SARS CoV-2 specific antibodies in human milk at higher levels compared to the initial primary series. This finding suggests that three doses of COVID-19 mRNA vaccination leads to improved mucosal response in human milk and reinforces current guidance recommending all pregnant or lactating mothers receive full COVID-19 vaccine courses with a booster dose.

Keywords: COVID-19; IgA; breastfeeding; breastmilk; immunization; infant; pregnancy; serology.

Figure 1

Human milk SARS-CoV-2-specific IgG, IgA, and IgM of antibody levels and neutralizing activity at pre-vaccination: 1-, 3-, 6-, and 9-months post-primary initial vaccine and 1-month post-booster vaccine dose. The median level of SARS-CoV-2-specific IgG, IgA, and IgM and neutralization activity at the 1-month post-booster time point was compared to the peak post-primary vaccination and pre-booster time points in human milk (A–D), respectively]. Dotted lines in y-axis indicate the positive cut-off OD₄₉₀ values of 0.20, 0.21, and 0.13 for IgG, IgA, IgM, respectively. Dotted line in y-axis of (D) indicate the positive cut-off of 25% neutralizing activity. Wilcoxon matched pairs signed rank tests were used for statistical analysis. Error bars indicate 95% confidence intervals.

Figure 2

Correlation between paired human milk and blood SARS-CoV-2-specific antibody. Forty-one paired human milk and blood samples collected at the same time point were included in the correlation analysis. Each color point represents each visit. The level of SARS-CoV-2-specific IgG (A) and IgA (B) in breastmilk showed positive correlations with the same isotypes in blood. Correlations were computed using Spearman correlation coefficient labeled ρ.