key: cord-0989033-8itrl7m9 authors: Esteve-Palau, E.; Gonzalez-Cuevas, A.; Guerrero, M. E.; Garcia-Terol, C.; Alvarez, M. C.; Garcia-Aranda, G.; Casadevall, D.; Diaz-Brito, V. title: Quantification of specific antibodies against SARS-CoV-2 in breast milk of lactating women vaccinated with an mRNA vaccine date: 2021-04-07 journal: nan DOI: 10.1101/2021.04.05.21254819 sha: 07ae4b6b51b10516980c53503c9a03a59d507dc2 doc_id: 989033 cord_uid: 8itrl7m9 INTRODUCTION The recent approval of vaccines against COVID-19 has generated great concern among breastfeeding women, since these patients were excluded from vaccination clinical trials. The present study aimed to analyze the levels of specific SARS-CoV-2 antibodies in breast milk of mRNA-vaccinated women across time and their correlation with serum antibody levels. METHODS Prospective study including lactating women aged over 18 who were vaccinated against SARS-CoV-2 with the Pfizer-BioNTech(R) COVID-19 vaccine (BNT162b2). Paired serum and breast milk samples were simultaneously taken from each participant at three timepoints after receiving the vaccine: 2 weeks after 1st dose, 2 weeks after 2nd dose and 4 weeks after 2nd dose (Timepoints 1, 2 and 3, respectively). Levels of IgG antibodies against the spike protein (S1 subunit) were determined for each sample (Architect, Abbott(R)). RESULTS We collected and analyzed 52 serum and 52 milk samples from the first 18 study participants. Median (interquartile range) IgG(S1) levels for serum - milk pairs at each timepoint were 410 (208-606) - 1.7 (0-2.9) AU/ml at Timepoint 1, 11505 (8933 - 21184) - 52.2 (34.1-113) at Timepoint 2 and 8311 (5578-17419) - 41.7 (24.8-75.3) at Timepoint 3. Pearson's correlation coefficient between breast milk and serum IgG(S1) levels was 0.71. No major adverse reactions were observed in mothers or infants. CONCLUSIONS Breast milk from women vaccinated with mRNA-based Pfizer-BioNTech(R) vaccine contains specific anti-SARS-CoV-2 IgG(S1) antibodies, with levels increasing considerably after second dose. IgG(S1) levels in breast milk are positively correlated with corresponding serum levels. breast milk samples were simultaneously taken from each participant at three timepoints after receiving the vaccine: 2 weeks after 1 st dose, 2 weeks after 2 nd dose and 4 weeks after 2 nd dose (Timepoints 1, 2 and 3, respectively). Levels of IgG antibodies against the spike protein (S1 subunit) were determined for each sample (Architect, Abbott®). . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 7, 2021. ; https://doi.org/10.1101/2021.04.05.21254819 doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. Results: we collected and analyzed 52 serum and 52 milk samples from the first 18 study participants. Median (interquartile range) IgG(S1) levels for serum -milk pairs at each timepoint were 410 (208-606) -1.7 (0-2.9) AU/ml at Timepoint 1, 11505 (8933 -21184) -52.2 (34. at Timepoint 2 and 8311 (5578-17419) -41.7 (24. .3) at Timepoint 3. Pearson's correlation coefficient between breast milk and serum IgG(S1) levels was 0.71. No major adverse reactions were observed in mothers or infants. Conclusions: Breast milk from women vaccinated with mRNA-based Pfizer-BioNTech® vaccine contains specific anti-SARS-CoV-2 IgG(S1) antibodies, with levels increasing considerably after second dose. IgG(S1) levels in breast milk are positively correlated with corresponding serum levels. . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 7, 2021. The current COVID-19 pandemic caused by SARS-CoV-2 has caused great concern among breastfeeding women, both because of the possibility of viral transmission to infants during breastfeeding and, more recently, of potential harmful effects of vaccination in this specific population. At the beginning of the vaccination campaign in our center, multiple healthcare professionals who were breastfeeding consulted our Infectious Disease Department, concerned about vaccination against COVID. Their main concern was whether breastfeeding was a contraindication to vaccination and, therefore, they felt they had to choose between being vaccinated or ending breastfeeding, since they were considered at high risk of infection. Although pregnant and lactating women have not been included in the clinical trials for the approval of these vaccines, the main official bodies and scientific associations consider mRNA vaccines as low risk for lactation and, therefore, they recommend its administration in cases where the risk of contracting the disease may be higher than the potential risks of vaccination [1] [2] [3] [4] [5] . Recent studies have shown that milk produced by infected mothers is a source of anti-SARS-CoV-2 antibodies 6 , and two reports have demonstrated the existence of anti-SARS-CoV-2 antibodies in women vaccinated with Moderna® and Pfizer-BioNTech® mRNA vaccines 7, 8 . If this exerts a protective effect for breastfed infants remains to be established. In the present study, we characterize the levels of specific SARS-CoV-2 antibodies in the breast milk of mRNA-vaccinated women across time, as well as their correlation with serum antibody levels. This prospective study included lactating women aged over 18 who were vaccinated against SARS-CoV2 with the Pfizer-BioNTech® COVID-19 vaccine (BNT162b2). The study received approval from our institution's Ethics Committee (CEIm Fundació Sant Joan de Déu) with approval code PIC-28-21. All participants signed the corresponding informed consent. . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 7, 2021. ; https://doi.org/10.1101/2021.04.05.21254819 doi: medRxiv preprint Serum and breast milk samples were simultaneously taken from each participant at three timepoints: after receiving the first dose of the vaccine (timepoint 1), at two weeks-(timepoint 2) and four weeks after second dose (timepoint 3). At the same time, all participants underwent a nasopharyngeal smear for SARS-CoV-2 rapid antigen test determination (Ag-RDT). Levels of IgG antibodies against the spike protein (S1 subunit) and against the nucleocapsid (NC) of SARS-CoV-2 were determined for each sample (Architect, Abbott®). All statistical analyses were performed with R version 4.0.3 (2020-10-10) and figures were generated using the ggplot2 R package. Here we demonstrated that breast milk from women vaccinated with the novel mRNA-based Pfizer-BioNTech® vaccine contains specific anti-SARS-CoV-2 IgG(S1) antibodies. Furthermore, we showed that breast milk IgG(S1) levels dramatically increase after the second dose and that they are positively correlated with corresponding serum levels. This promising finding argues in favor of a potential protective effect of breastfeeding mothers' vaccination in their infants. It . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted April 7, 2021. ; https://doi.org/10.1101/2021.04.05.21254819 doi: medRxiv preprint remains to be determined if breast milk antibody levels decrease or plateau after vaccination, or whether these findings can be reproduced for other mRNA and non-mRNA-based vaccines. The kinetics of IgG and other specific immunoglobulins against SARS-CoV-2 such as IgA and IgM have been well studied after the disease 13 , mainly in serum but also in breast milk 14 , although their dynamics after vaccination remain unknown. Larger prospective studies examining these issues are needed to confirm the safety of SARS-CoV-2 vaccination in breastfeeding women and its impact on their infants' health and SARS-CoV-2-specific immunity. Regarding the present study, accrual is still ongoing, and we plan to publish the results of more in-depth analysis in an expanded cohort of participants. Breast milk from women vaccinated with mRNA-based Pfizer-BioNTech® vaccine contains specific anti-SARS-CoV-2 IgG(S1) antibodies, with levels increasing considerably after second dose. IgG(S1) levels in breast milk are positively correlated with corresponding serum levels. Breastfeeding could have a protective effect against COVID-19 for breastfed infants with All authors have seen and approved the manuscript. . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 7, 2021. ; https://doi.org/10.1101/2021.04.05.21254819 doi: medRxiv preprint Covid-19 Vaccine Frequently Asked Questions Characterization of SARS-CoV-2 RNA, Antibodies, and Neutralizing Capacity in Milk Produced by Women with COVID-19. mBio SARS-CoV-2 antibodies detected in human breast milk post-vaccination Yael Bahar et al. BNT162b2 COVID-19 mRNA vaccine elicits a rapid and synchronized antibody response in blood and milk of breastfeeding women The risks of not breastfeeding for mothers and infants Delayed breastfeeding initiation is associated with infant morbidity Timing of initiation, patterns of breastfeeding, and infant survival: Prospective analysis of pooled data from three randomised trials No compensation was received by any author for their role in this study, and all of them declare no conflicts of interest.. CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)The copyright holder for this preprint this version posted April 7, 2021. . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. IgG(S1) levels at the different timepoints. The scale on the Y-axis was transformed to log10 for visualization purposes and an offset of 0.03 was added to IgG1(S1) values to include 6 participants with undetectable antibody levels. . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)The copyright holder for this preprint this version posted April 7, 2021. ; https://doi.org/10.1101/2021.04.05.21254819 doi: medRxiv preprint