Vertical transfer of humoral immune protection after maternal SARS-CoV-2 vaccination
In a recent study posted to the Research Square* preprint server, researchers assessed the presence, durability, and neutralization potency of immunoglobulin G (IgG) and IgA antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in breastfeeding infant stools, maternal plasma, and breast milk following maternal coronavirus disease 2019 (COVID-19) vaccination.
Studies have reported that maternal COVID-19 vaccinations in pregnancy induce anti-SARS-CoV-2 spike (S) IgG antibodies in mothers; however, the placental transfer of SARS-CoV-2 neutralizing antibodies in human milk (HM) to breastfed infants and their immune protective effects against COVID-19 need further research.
About the study
In the present study, researchers assessed the potential transfer and immune protection conferred by neutralizing anti-SARS-CoV-2 IgG and IgA HM antibodies in breastfed infants.
Lactating mothers aged ≥18 years (n=37) were recruited for the study before or after COVID-19 vaccination with Moderna, Johnson & Johnson, or Pfizer/BioNTech messenger ribonucleic acid (mRNA) COVID-19 vaccines between December 2020 and November 2021. Breastfed infants (n=25) were included in the study between June and November 2021 to analyze their stool samples.
Participants filled out questionnaires to provide data on maternal and/or infant demographics, family and medical history, and the impact of COVID-19 vaccinations. Breast milk, sera from mothers, and stool samples from their maternal infants were obtained before COVID-19 vaccination and at specific time intervals till six months post-COVID-19 vaccination.
Anti-SARS-CoV-2 IgG and IgA titers were measured using enzyme-linked immunosorbent assays (ELISA). For comparison, pre-COVID-19 era samples (n=10) and maternal pre-COVID-19 vaccination infant stool samples (n=1) were obtained as controls. SARS-CoV-2 neutralization potency of IgG and IgG antibodies was evaluated in the obtained samples using assays based on green fluorescent proteins (GFP) and SARS-CoV-2 S that express vesicular stomatitis virus (VSV).
VSV-mixed HM, sera, and samples of infant stools were incubated with human angiotensin-converting enzyme 2 (ACE2)-expressing BHK (baby hamster kidney) cells. Subsequently, GFP frequencies were assessed by FC (flow cytometry) for quantitative assessment of BHK-ACE2 cells’ infectivity. The half maximal inhibitory concentration (IC50) values were calculated for all samples and fed into non-linear type regression models for the analysis.
Results
In total, 97, 102, and 32 samples of maternal sera, maternal HM, and infant stool were obtained, respectively, at several time points viz. pre-vaccination, after 15 to 30 days of initial vaccination, and at seven to 30 days, 60 to 75 days, 90 to 105 days, and after six months of double COVID-19 vaccination. Most participants were aged 30 to 40 years, and the median age of infants at enrollment was ten months.
Anti-SARS-CoV-2 IgG and IgA titers were greater in infant stools after mothers’ SARS-CoV-2 vaccination among breastfed infants than in pre-COVID-19 controls. HM and sera anti-SARS-CoV-2 IgG and IgA titers reduced after six months of vaccination but persisted above the pre-vaccination titers. SARS-CoV-2 neutralization was found to increase with time.
The average IC50 values among infant stools post-maternal vaccination and controls were 0.9 and 1.4, respectively, and SARS-CoV-2 neutralization by infant stool antibodies post-maternal vaccination was higher than controls by 30%. For HM, median values of log (10)-transformed IgA titers before and after six months of COVID-19 vaccination were 1.3 and 1.6 units/ml, respectively. In sera, the corresponding medians were 3.3 and 3.5 units/ml.
Positivity rates reduced from 85% after seven to 30 days of vaccination to 50% and 74% among HM and sera, respectively, six months post-vaccination. Serum IgA titers after six months of vaccination correlated positively with sera IgG titers. Median log (10)-transformed HM anti-SARS-CoV-2 IgG titers pre-vaccination and six months post-vaccination of 0.1 and 0.6 units/ml, respectively, were observed.
In sera samples, a sharp drop in anti-SARS-CoV-2 IgG titers was observed six months post-COVID-19 vaccination than those observed after double COVID-19 vaccination. However, positivity rates persisted >90% beyond six months in HM and sera. After six months of COVID-19 vaccination, sera IgA and HM IgG titers correlated positively.
For HM and sera, an overall reduction was observed for anti-SARS-CoV-2 titers after six months of COVID-19 vaccination compared to those observed seven to 30 days after COVID-19 vaccination, especially for anti-SARS-CoV-2 IgG titers. However, the elevation in anti-SARS-CoV-2 IgG titers after COVID-19 vaccinations was especially prominent for IgG titers compared to IgA titers. HM neutralized SARS-CoV-2 in vitro before and after vaccination with the greatest SARS-CoV-2 neutralization post-six months of SARS-CoV-2 vaccinations.
The average IC50 values for breast milk before and after six months of vaccination were 0.1 and 0.03, respectively, with a 75% increase in neutralization titers six months post-vaccination. Average sera IC50 values pre-vaccination, seven to 30 days post-vaccination and six months post-vaccination were 0.5, 0.001 and 0.04, respectively. A 99% increase in neutralization titers was found in sera post-vaccination that persisted at significantly greater levels than before vaccination.
Overall, the study findings showed the transfer of and long-term durability of maternal neutralizing antibodies against SARS-CoV-2 to infant stools after maternal COVID-19 vaccinations, underscoring the long-term durability of maternal anti-SARS-CoV-2 antibody titers transferred via breast milk and their immune protective effects.
*Important notice
Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
