ABSTRACT
Anti-SARS-CoV-2 antibodies have been found in human-milk after COVID-19 infection and vaccination. However, little is known about their persistence in milk after booster vaccination and breakthrough infection. In this study, human-milk, saliva and blood samples were collected from 33 lactating individuals before and after mRNA-based vaccination and COVID-19 breakthrough infections. Antibody levels were measured using ELISA and symptoms were assessed using questionnaires. Evaluation of maternal and infant symptomatology revealed that infected mothers reported more symptoms than vaccinated mothers. We found that after vaccination, human-milk anti-SARS-CoV-2 antibodies persisted for up to 8 months. In addition, distinct patterns of human milk IgA and IgG production we observed after breakthrough infection compared to 3-dose vaccination series alone, indicating a differential central and mucosal immune profiles in hybrid compared with vaccine-induced immunity. To investigate passively-derived milk antibody protection in infants, we examined the persistence of these antibodies in infant saliva after breastfeeding. We found that IgA was more abundant in infant saliva compared to IgG and persist in infant saliva longer after feeding. Our results delineate the differences in milk antibody response to vaccination as compared to breakthrough infection and emphasize the importance of improving the secretion of IgA antibodies to human milk after vaccination to improve the protection of breastfeeding infants.
ABSTRACT
Multiple SARS-CoV-2 variants that possess mutations associated with increased transmission and antibody escape have arisen over the course of the current pandemic. While the current vaccines have largely been effective against past variants, the number of mutations found on the Omicron (B.1.529) spike appear to diminish the efficacy of pre-existing immunity. Using pseudoparticles expressing the spike of several SARS-CoV-2 variants, we evaluated the magnitude and breadth of the neutralizing antibody response over time in naturally infected and in mRNA-vaccinated individuals. We observed that while boosting increases the magnitude of the antibody response to wildtype (D614), Beta, Delta and Omicron variants, the Omicron variant was the most resistant to neutralization. We further observed that vaccinated healthy adults had robust and broad antibody responses while responses were relatively reduced in vaccinated pregnant women, underscoring the importance of learning how to maximize mRNA vaccine responses in pregnant populations. Findings from this study show substantial heterogeneity in the magnitude and breadth of responses after infection and mRNA vaccination and may support the addition of more conserved viral antigens to existing SARS-CoV-2 vaccines. One Sentence SummaryDiminished efficacy of pre-existing immunity to highly mutated SARS-CoV-2 variants.
ABSTRACT
Pregnancy confers unique immune responses to infection and vaccination across gestation. To date, there is limited data comparing vaccine versus infection-induced nAb to COVID-19 variants in mothers during pregnancy. We analyzed paired maternal and cord plasma samples from 60 pregnant individuals. Thirty women vaccinated with mRNA vaccines were matched with 30 naturally infected women by gestational age of exposure. Neutralization activity against the five SARS-CoV-2 Spike sequences was measured by a SARS-CoV-2 pseudotyped Spike virion assay. Effective nAbs against SARS-CoV-2 were present in maternal and cord plasma after both infection and vaccination. Compared to wild type or Alpha variant Spike, these nAbs were less effective against the Kappa, Delta, and Mu Spike variants. Vaccination during the third trimester induced higher nAb levels at delivery than infection during the third trimester. In contrast, vaccine-induced nAb levels were lower at the time of delivery compared to infection during the first trimester. The transfer ratio (cord nAb level/maternal nAb level) was greatest in mothers vaccinated in the second trimester. SARS-CoV-2 vaccination or infection in pregnancy elicit effective nAbs with differing neutralization kinetics that is impacted by gestational time of exposure. Vaccine induced neutralizing activity was reduced against the Delta, Mu, and Kappa variants. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=155 HEIGHT=200 SRC="FIGDIR/small/21267557v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@4225dborg.highwire.dtl.DTLVardef@c35b5borg.highwire.dtl.DTLVardef@1a2d180org.highwire.dtl.DTLVardef@6863c2_HPS_FORMAT_FIGEXP M_FIG C_FIG
