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.

SARS-CoV-2-Specific IgG and IgA response in maternal blood and breastmilk of vaccinated naïve and convalescent lactating participants

“…In contrast to that observed for IgA, a significant decreased was observed in IgG levels both in serum and breastmilk pared samples. These results are in agreement with previous studies using mRNA-based vaccines that showed increased IgG levels after the first and second doses, with a significant reduction thereafter ( 35 , 37 , 38 ).…”

“…This rapid increase of IgG after the second dose is consistent with a specific B lymphocyte memory that will prime a faster response with higher antibodies levels ( 33 ). In contrast, we observed that the IgA levels remained constant between the two doses, as it was reported in previous studies with adenoviral-based vaccines (Ad26.COV2.S and ChAdOx1‐S) ( 27 , 28 , 35 ). Heterogeneous dynamics in IgG and IgA antibody levels can be associated to their diverse functions.…”

SARS-CoV-2 Vaccine Booster Elicits Robust Prolonged Maternal Antibody Responses and Passive Transfer Via The Placenta And Breastmilk

“…24 Our results confirm earlier conclusions that the initial two dose vaccination series during gestation resulted in appreciable RBD-specific IgG response in maternal circulation, UCB, and breastmilk. 20, 27 Importantly, longitudinal analysis of post-partum samples indicates that the booster dose is essential for producing higher and more durable antibody levels in both maternal circulation and breastmilk, 28, 29, 42 and should be strongly encouraged for all pregnant people to increase neonatal passive immune protection against SARS-CoV-2.…”

“…20, 27 Moreover, booster vaccinations led to increased levels of maternal IgG1 and IgA antibodies in umbilical cord blood 28 and breastmilk. 29…”

“…20,27 Moreover, booster vaccinations led to increased levels of maternal IgG1 and IgA antibodies in umbilical cord blood 28 and breastmilk. 29 For some pregnant individuals, vaccination decisions are highly influenced by a primary goal to protect neonatal health. Thus, their decision as to whether to receive primary or booster vaccinations during pregnancy or to delay vaccination until a later gestational age or postpartum are shaped by knowledge about impact of vaccine timing and duration of protection.…”