Both pregnant and lactating women raised FcR-binding serum antibodies after the second dose. Nevertheless, all FcR-binding antibodies in pregnant women and FcγR2b-binding antibodies in lactating women remained lower as compared to the non-pregnant women. The team suggests that these higher FcR-binding profiles in lactating and non-pregnant women could be linked to enhanced coordination in the humoral immune responses compared to pregnant women.
All three populations induced similar antibody-dependent cellular phagocytosis (ADCP) and did not increase ADCP function post-boost vaccination. In contrast, antibody-dependent neutrophil phagocytosis (ADNP) activity was increased in pregnant and lactating women after boosting.
Overall, these data point to restriction in the ability of pregnant women to generate functional, but not total, antibodies with boosting compared to lactating women. Further, these data suggest that pregnant and lactating women show potential early alterations in vaccine-induced immune responses that improve after a booster vaccine.
Maternal blood had a higher titer of antibodies compared to cord blood. Variable patterns of transfer of IgG titer, FcR-binding and antibody function were observed from the mother to the cord. Despite the recency of vaccination, equivalent, IgG1 spike protein-specific titers were transferred across the placenta to the infant.
Stable phagocytic antibodies but decreased NK-cell activating antibodies were transferred to infants. However, despite the lower titers of antibodies in the cord, the placenta was able to select for FcγR3a-binding, functionally enhanced vaccine-induced antibodies.
Boosting enhances transfer of FcR-binding IgG antibodies in breastmilk. Lactating mother serum had a preferential boosting of FcR-binding IgG responses after a booster vaccine dose. The team observed the transfer of a similar profile to the breastmilk, with high IgG antibodies and high FcR-binding capabilities post-boost.
“Vaccination appears to augment highly functional IgG transit to the milk that is likely key to antiviral immunity across viral pathogens,” the team highlights.
NK-cell activating antibodies had a low transfer ratio at the post-boost timepoint, suggesting a sieve at the mammary gland, preventing the transfer of highly inflammatory antibodies through breastmilk.
mRNA-1273 vaccinated women exhibited more focused coordination in the humoral immune response, centered around a high IgG1/IgG3 response with robust FcR-binding and functional coordination. Conversely, women receiving BNT162b2 generated a broader coordinated immune response, including IgG2 and IgM responses and the exclusion of monocyte phagocytosis (ADCP), suggesting a more diffuse overall humoral immune coordination profile.
These serum differences translated to differences in antibodies transferred in breastmilk. In addition, the team observed differences in the overall antibody profile across women receiving mRNA-1273 and BNT162b2.
Thus, as per the team’s speculation, the extra week prior to mRNA-1273 boosting may provide the time needed for the humoral immune response to mature, resulting in more functional antibody profiles.
These findings collectively point to an extended window of vulnerability in pregnancy and lactation following vaccination, requiring timely boosting to achieve fully-functional antibodies that can protect pregnant individual and their infant.