Non-neutralizing secretory IgA and T cells targeting SARS-CoV-2 spike protein are transferred to the breastmilk upon BNT162b2 vaccination

Abstract

In view of data scarcity to guide decision-making in breastfeeding women, we evaluated how mRNA vaccines impact immune response of lactating health care workers (HCW) and the effector profile of breast milk transferred immune protection. We show that upon BNT162b2 vaccination, immune transfer via milk to suckling infants occurs through secretory IgA (SIgA) and T cells. Functionally, spike-SIgA was non-neutralizing and its titers were unaffected by vaccine boosting, indicating that spike-SIgA is produced in a T-cell independent manner by mammary gland. Even though their milk was devoid of neutralizing antibodies, we found that lactating women had higher frequencies of RBD-reactive circulating memory B cells and more RBD-IgG antibodies, when compared to controls. Nonetheless, blood neutralization titers in lactating and non-lactating HCW were similar. Further studies are required to determine transferred antibodies and spike-T cells complete functional profile and whether they can mediate protection in the suckling infant.HighlightsMilk and blood responses to BNT162b2 vaccine are initially isotype discordantImmune transfer via milk to suckling infants occurs by spike-reactive SIgA and T cellsSpike-reactive SIgA in the breastmilk is non-neutralizing and T-cell independentLactating vs non-lactating HCW had distinct cellular responses, despite similar NT50

COVID-19 mRNA Vaccination in Lactation: Assessment of Adverse Events and Vaccine Related Antibodies in Mother-Infant Dyads

“…In our study IgA levels in milk were measured 4-10 weeks post 2nd dose and based on other publications we expect that milk IgA levels will be relatively lower at this stage in compared to 10-14 days after 2nd dose. These differences in the timing of measurements might explain the differences in our findings, compared to other studies ( 32 , 35 ). Although we did not measure maternal blood IgA, other studies have shown that blood and milk IgA levels correlate when measured 7-10 days after the 2nd dose ( 13 , 36 ).…”

DataSheet_1.docx

“…Ten out of the 12 participants who had no detectable anti-RBD IgA, had infants older than 5.5 months at the time of sample collection. These findings are different from other publications that showed positive correlation of milk IgA levels (measured 2 weeks after 2nd dose) and baby age (32) or another study that didn't show correlation between these antibodies titters in milk and infant age (10 days after 2nd dose) (35). In our study IgA levels in milk were measured 4-10 weeks post 2nd dose and based on other publications we expect that milk IgA levels will be relatively lower at this stage in compared to 10-14 days after 2nd dose.…”

“…In our study IgA levels in milk were measured 4-10 weeks post 2nd dose and based on other publications we expect that milk IgA levels will be relatively lower at this stage in compared to 10-14 days after 2nd dose. These differences in the timing of measurements might explain the differences in our findings, compared to other studies (32,35). Although we did not measure maternal blood IgA, other studies have shown that blood and milk IgA levels correlate when measured 7-10 days after the 2nd dose (13,36).…”

Development of Triazoles and Triazolium Salts Based on AZT and Their Anti-Viral Activity against HIV-1

“…However, primary T cells isolated from human donors can be distinctively affected by HIV-1 infection. Thus, we determined the ability of the compounds to block HIV-1 replication in human primary CD4 T cells isolated from peripheral blood [28,29]. Thus, peripheral blood mononuclear cells (PBMCs) from healthy human donors were isolated and infected ex vivo with HIV-1 NL4.3 [30].…”

“…Schematic representation of methodological approach. Human peripheral blood cells were isolated from whole blood through gradient centrifugation [28,29,31]. Primary CD4 + T cells were infected with a GFP-tagged HIV-1 NL4.3 virus for 5 days [30].…”