Anti-Sars-Cov-2 IgA And IgG In Human Milk After Vaccination Is Dependent On Vaccine Type And Previous Sars-Cov-2 Exposure: A Longitudinal Study

Abstract

Importance: Limited data are available on COVID-19 vaccine impact in lactating women. Objective: To evaluate the impact of different COVID-19 vaccines on specific anti-SARS-CoV-2 IgA and IgG levels in human milk. Design, Settings and Participants: In this prospective observational study in Spain, 75 lactating women from priority groups receiving vaccination against SARS-CoV-2 were included (January to April 2021). Human milk samples were collected at seven-time points. A group with confirmed SARS-CoV-2 infection (n=19) and a group of women from prepandemic time (n=13) were included. Exposure: mRNA vaccines (BNT162b2 and mRNA-1273) and adenovirus-vectored vaccine (ChAdOx1 nCoV-19). Main Outcome(s) and Measure(s): Presence of IgA and IgG against RBD SARS-CoV-2 in breast milk. Results: Seventy-five vaccinated lactating women [mean age, 34.9±3.7 years] of whom 96% were Caucasic and 92% were health care workers. A total of 417 milk samples were included and vaccine distribution was BioNTech/Pfizer (BNT162b2, n=30), Moderna (mRNA-1273, n=21), and AstraZeneca (ChAdOx1 nCoV-19, n=24). For each vaccine, 7 time points were collected from baseline up to 25 days after the 1st dose and same points were collected for mRNA vaccines 30 days after 2nd dose. A strong reactivity was observed for IgG and IgA after vaccination mainly after the 2nd dose. Presence and the persistence of specific SARS-CoV-2 antibodies in breast milk were dependent on the vaccine-type and, on previous virus exposure. High inter-variability was observed, being relevant for IgA antibodies. IgG levels were significantly higher than those observed in milk from COVID-19 women while IgA levels were lower. Women with previous COVID-19 increased the IgG levels after the 1st dose to a similar level observed in vaccinated women after the 2nd dose. Conclusions and Relevance: Breast milk from vaccinated women contains anti-SARS-CoV-2 IgA and IgG, with highest after the 2nd dose. Levels were dependent on vaccine type and previous exposure to SARS-CoV-2. Previous COVID-19 influenced the vaccine effect after a single dose, which could be especially relevant in the design of vaccination protocols . Further studies are warranted to demonstrate the potential protective role of these antibodies against COVID-19 in infants from vaccinated and infected mothers through breastfeeding.

Survival of vaccine-induced human milk SARS-CoV-2 IgG and IgA immunoglobulins across simulated human infant gastrointestinal digestion

“…Furthermore, in another study of 84 lactating women, milk IgA secretion was observed 2 weeks after vaccination with the first dose of Pfizer-BioNTech vaccine while IgG secretion was observed a week after the administration of the second dose (Perl et al, 2021). In agreement with a previous study (Selma-Royo et al, 2021) our results revealed that while both vaccines increased milk anti-SARS-CoV-2 IgA levels, Pfizer-BioNTech induced higher IgG levels than Astra Zeneca vaccine after administration of the 2 nd dose. Moreover, mRNA-based vaccines induced their maximum effect after the administration of the 2 nd dose.…”

Neutralizing Activity and SARS-CoV-2 Vaccine mRNA Persistence in Serum and Breastmilk After BNT162b2 Vaccination in Lactating Women

“…These findings are concordant with previously reported increases in breastmilk SARS-CoV-2-specific IgA and IgG levels within a week after the second vaccine dose ( 10 , 11 , 27 , 28 ). SARS-CoV-2 specific IgA in the breastmilk reportedly achieved maximal levels a week after the second dose, where SARS-CoV-2-specific IgG was only evident 1 week after the second dose ( 12 , 14 , 28 – 31 ). The persistence of neutralizing activity up to 3 weeks post dose 2 corresponds to the continued elevation in SARS-CoV-2 RBD-specific IgG1 but not IgA levels.…”

Anti-SARS-CoV-2 IgA and IgG in Human Milk From Vaccinated Mothers After Holder Pasteurization

“…Then, BM was collected using a sterile pump in sterile bottles to normalize the milk collection. Samples included in the analysis were collected 15-20 days after the second dose of SARS-CoV-2 vaccine when the maximum immunological response in terms of antibody production has been reported (13)(14)(15). Samples were kept at -20°C until transferred to the laboratory where they were stored at -80°C until further analysis.…”

“…Samples were diluted 1:4 before analysis and a standard curve was included in each plate to facilitate the analysis of the immunoglobulin levels. The standard curve consisted in ten 3fold serial dilutions from a mixture of samples (n = 10) that had been tested in previous studies (13,14), and showed higher levels of both Ig concentrations. These milk samples were collected from mothers vaccinated against SARS-CoV-2 at 20 days after the second dose since a previous study showed higher levels of antibodies in that period (14).…”