Comparing the human milk antibody response after vaccination with four COVID-19 vaccines: A prospective, longitudinal cohort study in the Netherlands

Background Vaccination of lactating women against COVID-19 may protect not only themselves but also their breastfed infant through human milk. Therefore, it is important to gain insight into the human milk antibody response after immunization with the various vaccines that are currently widely used. The aim of this study is to determine and compare the antibody response in human milk following vaccination with mRNA-and vector-based vaccines up to over two months post-vaccination. Methods This prospective cohort study was conducted in the Netherlands between January 06, 2021 and July 31, 2021. Participants were recruited through social media. Human milk samples were collected longitudinally during a period of 70 days from women receiving one of the four different severe acute respiratory coronavirus 2 (SARS-CoV2) vaccines: Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), Oxford/AstraZeneca (AZD1222) and Johnson & Johnson (Ad26.COV2.S). SARS-CoV-2-specific antibodies were measured using an enzyme-linked immunosorbent assay. The area under the curve (AUC) of the Immunoglobulins A (IgA) and G (IgG) antibody response was determined over 15 and 70 days following the first vaccination and compared between the different vaccines. Findings This study enrolled 134 vaccinated lactating women of whom 97 participated the entire study period. In total, 1887 human milk samples were provided. The human milk antibody response differed between SARS-CoV-2 vaccines over the study period. The mean AUC of SARS-CoV-2-specific IgA, but not IgG, in human milk over 15 days was higher after vaccination with an mRNA-based vaccine than a vector-based vaccine (AUC with respect to ground [AUCg] & PLUSMN; the standard error of the mean [SEM] for IgA was 6.09 & PLUSMN; 0.89 in the BNT162b2 group, 7.48 & PLUSMN; 1.03 in the mRNA-1273 group, 4.17 & PLUSMN; 0.73 in the AZD1222 group, and 5.71 & PLUSMN; 0.70 in the Ad26.COV2.S group). Over a period of 70 days, the mean AUCg of both IgA and IgG was higher after vaccination with an mRNA-based vaccine than a vector-based vaccine (AUCg & PLUSMN; SEM for IgA was 38.77 & PLUSMN; 6.51 in the BNT162b2 group, 50.13 & PLUSMN; 7.41 in the mRNA-1273 group, 24.12 & PLUSMN; 5.47 in the AZD1222 group, and 28.15 & PLUSMN; 6.69 in the Ad26.COV2.S group; AUCg & PLUSMN; SEM for IgG was 40.43 & PLUSMN; 2.67 in the BNT162b2 group, 37.01 & PLUSMN; 2.38 in the mRNA-1273 group, 16.04 & PLUSMN; 5.09 in the AZD1222 group, and 10.44 & PLUSMN; 2.50 in the Ad26.COV2.S group). Interpretation Overall, maternal vaccination during lactation with an mRNA-based vaccine resulted in higher SARS-CoV-2 antibody responses in human milk compared to vector-based vaccines. Therefore, vaccination with mRNA-based vaccines, preferably with the mRNA-1273 vaccine, might not only provide better immunological protection for the mother but also for her breastfed infant.