Anti-Spike Antibodies Present in the Milk of SARS-CoV-2 Vaccinated Mothers Are Complement-Activating

Abstract

Although only 0.8–1% of SARS-CoV-2 infections are in the 0–9 age-group, pneumonia is still the leading cause of infant mortality globally. Antibodies specifically directed against SARS-CoV-2 spike protein (S) are produced during severe COVID-19 manifestations. Following vaccination, specific antibodies are also detected in the milk of breastfeeding mothers. Since antibody binding to viral antigens can trigger activation of the complement classical - pathway, we investigated antibody-dependent complement activation by anti-S immunoglobulins (Igs) present in breast milk following SARS-CoV-2 vaccination. This was in view of the fact that complement could play a fundamentally protective role against SARS-CoV-2 infection in newborns. Thus, 22 vaccinated, lactating healthcare and school workers were enrolled, and a sample of serum and milk was collected from each woman. We first tested for the presence of anti-S IgG and IgA in serum and milk of breastfeeding women by ELISA. We then measured the concentration of the first subcomponents of the three complement pathways (i.e., C1q, MBL, and C3) and the ability of anti-S Igs detected in milk to activate the complement in vitro. The current study demonstrated that vaccinated mothers have anti-S IgG in serum as well as in breast milk, which is capable of activating complement and may confer a protective benefit to breastfed newborns.

Anti-SARS-CoV-2 Immunoglobulins in Human Milk after Coronavirus Disease or Vaccination—Time Frame and Duration of Detection in Human Milk and Factors That Affect Their Titers: A Systematic Review

“…As for the factors influencing antibody levels in HM, numerous studies have confirmed a significant positive correlation between IgG titers in HM and maternal serum [25,29,45,47,48,51,56,[62][63][64]69,75,77,79,80]. A positive correlation between the lactation period and the total antibody titers was also reported in a study by Trofin F. et al (lactating period between 3 and 36 months) [57].…”

“…A recent longitudinal study reported that IgG antibodies' half lives in HM are about 2 months [45]. In other relevant studies, no significant difference in IgG titers was observed between 30 and 60 days post vaccination [57,80]. Even IgG levels wane over time, but remain in detectable levels 2 [57], 3 [38,53,72] and 6 months post vaccination [49,73].…”

“…The main IgG subclasses in HM after 2 doses of mRNA-based vaccines are IgG1 and IgG3, which are the main subclasses of IgG that emerge after viral infections [45,97]. Interestingly, Agostinis C. et al, in a recent study, demonstrated that the presence of anti-S IgG in the HM of vaccinated lactating women is capable of activating in vitro the complement [80]. All of these data indicate that vaccinated mothers are capable of providing protective antibodies to their offspring for a long time after their primary vaccination.…”

“…On the other hand, IgG antibodies produced post vaccination have been found to be capable of activating the complement. Therefore, infants can benefit from both types of antibodies in different ways [80].…”

The last word on COVID-19 vaccines and breastfeeding?

“…Recent scientific literature has mainly focused on determining the presence and functionality of anti-Spike protein antibodies in the milk of vaccinated women, 2 , 3 but only few studies have investigated the levels of BNT162b2 or mRNA-1273 mRNA in BM. 4 Golan et al., analyzing 13 BM samples collected from 7 breastfeeding women 24 h after vaccination -including multiple time points, up to 48 h, from a single participant-have initially neglected the presence of vaccine-associated mRNA.…”