key: cord-0967203-16oh8xb1 authors: Golan, Y.; Prahl, M.; Cassidy, A.; Wu, A. H. B.; Jigmeddagva, U.; Lin, C. Y.; Gonzalez, V. J.; Basilio, E.; Warrier, L.; Buarpung, S.; Asiodu, I. V.; Ahituv, N.; Flaherman, V. J.; Gaw, S. L. title: Immune response during lactation after anti-SARS-CoV2 mRNA vaccine date: 2021-03-12 journal: medRxiv DOI: 10.1101/2021.03.09.21253241 sha: e2a281d705d6715895e40ff0243cbb0073d9c142 doc_id: 967203 cord_uid: 16oh8xb1 Importance: Data regarding efficacy and safety of anti-COVID-19 mRNA vaccines during lactation is needed to address vaccination guidelines, ease vaccine hesitancy concerns, and inform public health strategies for this population. Objective: To determine whether anti-COVID-19 mRNA-based vaccines administered during lactation illicit an immune response or the transfer of anti-SARS-CoV2 antibodies into human milk. Design: Plasma and milk samples were collected from a prospective cohort of lactating individuals who received the mRNA-based vaccines for COVID-19 and from individuals who recovered from COVID-19 infection. Setting: Ambulatory or during postpartum hospitalization. Participants: We report results from lactating participants who received the mRNA-1273 (Moderna, n=9) or the BNT162b2 (Pfizer, n=14) vaccine or recovered from natural SARS-CoV-2 infection (n=3). Interventions and Exposures: Anti-COVID-19 mRNA vaccination (BNT-162b2 and mRNA-1273) or natural SARS-CoV-2 infection. Main Outcome(s) and Measure(s): Plasma and milk samples were collected from lactating individuals before first vaccine dose, on the day of the second dose, and 4 weeks after the second dose. Maternal plasma was evaluated for vaccine-derived IgM and IgG antibodies. Human milk was evaluated by ELISA for vaccine-induced IgA antibodies specific for SARS-CoV-2. Results: Twenty-three lactating individuals were recruited for this study. Levels of IgG and IgM were significantly increased in plasma samples on the day of the second vaccine dose (post vaccine 1), when compared to pre-vaccine samples. In addition, plasma IgG levels 4 weeks after second vaccine dose were significantly higher than plasma IgG levels pre-vaccine or on the day of the second dose. In addition, our results show transfer of anti-SARS-CoV2-Receptor Binding Domain (RBD) IgA antibodies to human milk, 3-4 weeks after each dose of the COVID-19 mRNA vaccines (BNT-162b2 and mRNA-1273). The levels of anti-SARS-CoV2-RBD IgA antibody in milk of vaccinated individuals were not significantly different from levels among participants who experienced SARS-CoV-2 infection. Conclusions and Relevance: Administration of anti-COVID-19 mRNA vaccines during lactation leads to increased anti-SARS-CoV2 IgM and IgG levels in the plasma of lactating mothers and increased anti-SARS-CoV2-RBD IgA levels in human milk. Lactating women who receive the vaccine should continue breastfeeding their infant human milk to allow continuing transfer of anti-SARS-CoV-2 IgA antibodies to the neonate. Additional studies are needed to evaluate the effect of these vaccines on lactation outcomes and infant health. Design: Plasma and milk samples were collected from a prospective cohort of lactating individuals who received the mRNA-based vaccines for COVID-19 and from individuals who recovered from COVID-19 infection. . CC-BY-NC-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 March 12, 2021. ; https://doi.org/10.1101/2021.03.09.21253241 doi: medRxiv preprint Setting: Ambulatory or during postpartum hospitalization. We report results from lactating participants who received the mRNA-1273 (Moderna, n=9) or the BNT162b2 (Pfizer, n=14) vaccine or recovered from natural SARS-CoV-2 infection (n=3). . CC-BY-NC-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. were assayed by ELISA for IgA antibodies specific to SARS-CoV-2 RBD protein. We analyzed 7 pre-vaccine, 12 post first vaccine administration, and 14 post second vaccine administration plasma samples from vaccinated lactating individuals. We found a significant increase in anti-SARS-CoV-2 IgM and IgG antibodies post first vaccine administration and post second vaccine administration, when compared to pre-vaccine samples (Figure 1A and 1B) . Furthermore, anti-SARS-CoV-2 IgG levels at 4 weeks after the second dose were significantly higher (P value <0.0001) compared to samples collected at 3-4 weeks after first dose (collected on the day of second dose) (Figure 1A) . In contrast, anti-SARS-CoV-2 IgM levels were not significantly higher 4 weeks after the second dose compared to samples collected after the first dose ( Figure 1B) . In addition, we found significantly higher levels of IgA antibodies specific to SARS-CoV-2 RBD protein in human milk samples collected after the first dose of both vaccines (Figure 2A and 2B ). Seventeen out of 19 milk samples analysed at the day of the second vaccine dose were . CC-BY-NC-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 March 12, 2021. ; https://doi.org/10.1101/2021.03.09.21253241 doi: medRxiv preprint positive for anti-SARS-CoV-2 IgA antibodies. Thirteen out of the 15 milk samples that were analysed 4 weeks after the second dose were positive for anti-SARS-CoV-2 RBD IgA (Figure 2A and 2B) . We also analyzed 3 milk samples collect from lactating individuals who were previously infected by SARS-CoV-2 virus. Anti-SARS-CoV-2 RBD IgA antibodies levels in milk samples from vaccinated individuals were not significantly different from samples collected after natural SARS-CoV-2 infection (Figure 2A and 2B, right columns) When analyzing serial samples collected from 0 to 64 days after first vaccine administration from 10 patients, we found variation in anti-SARS-CoV-2 RBD IgA antibodies levels in milk between individuals (Figure 2C and 2D) . In contrast to the significant increase in plasma IgG after the second dose ( Figure 1A) , milk IgA levels largely remained stable 4 weeks after the second dose ( Figure 2C ). We show here that administration of anti-COVID-19 mRNA vaccines during lactation leads to a significant increase in anti-SARS-CoV2 IgM and IgG levels in the plasma. Consistent with results from previous studies that showed reduced IgM levels 28 days after COVID-19 infection, 11 our results show that IgM levels 4 weeks post second dose administration were not significantly higher compared to their levels after the first dose. Furthermore, our data clearly demonstrate increased anti-SARS-CoV2-RBD IgA levels in human milk consistent with levels found after SARS-CoV-2 infection. Taken together, our findings suggest that anti-COVID-19 vaccination is beneficial for lactating individuals and may also protect their infants. Our results provide information needed to inform the care of lactating individuals and their infants 12 . Although there is expert consensus of minimal or no potential risk for the infant from maternal anti-COVID-19 vaccination 13, 14 , no previous studies have demonstrated specific benefits during lactation. Our results now provide such evidence. Future studies are needed to . CC-BY-NC-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 March 12, 2021. ; https://doi.org/10.1101/2021.03.09.21253241 doi: medRxiv preprint determine the degree of protection conferred by these IgA anti-SARS-CoV-2 antibodies. At the present time, our findings suggest that lactating individuals who receive vaccination should continue to breastfeed and chestfeed their infants in order to ensure transfer of anti-SARS-CoV-2 IgA antibodies to their baby that may potentially protect against COVID-19, important even during infancy 15 . Health care providers should continue to encourage lactating individuals to breastfeed and chestfeed their infant during and following COVID-19 vaccination. Emergency Use Authorization of Covid Vaccines -Safety and Efficacy Follow-up Considerations Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine The Moderna COVID-19 (mRNA-1273) vaccine: what you need to know Considerations for COVID-19 Vaccination in Lactation 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 COVID-19 mRNA vaccine is not detected in human milk. medRxiv Norovirus-specific immunoglobulin A in breast milk for protection against norovirus-associated diarrhea among infants Maternal antibodies in breast milk protect the child from enterovirus infections Robust and Specific Secretory IgA Against SARS-CoV-2 Detected in Human Milk Difference in levels of SARS-CoV-2 S1 and S2 subunits-and nucleocapsid protein-reactive SIgM/IgM, IgG and SIgA/IgA antibodies in human milk Patterns of IgG and IgM antibody response in COVID-19 patients COVID-19 Vaccination in Pregnant and Lactating Women The COVID-19 vaccine in pregnancy: risks benefits and recommendations 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 Coronavirus disease 2019 vaccines in pregnancy Epidemiology of COVID-19 infection in young children under five years: A systematic review and meta-analysis The authors declare no conflicts of interest. . CC-BY-NC-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. . CC-BY-NC-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. . CC-BY-NC-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 March 12, 2021. ; https://doi.org/10.1101/2021.03.09.21253241 doi: medRxiv preprint