A case series exploring the human milk polyclonal IgA1 response to repeated SARS-CoV-2 vaccinations by LC-MS based fab profiling

Sebastiaan C de Graaf; Albert Bondt; Danique M H van Rijswijck; Hannah G Juncker; Sien J Mulleners; Mirjam J A Damen; Max Hoek; Britt J van Keulen; Johannes B van Goudoever; Albert J R Heck; Kelly A Dingess

doi:10.3389/fnut.2023.1305086

A case series exploring the human milk polyclonal IgA1 response to repeated SARS-CoV-2 vaccinations by LC-MS based fab profiling

Front Nutr. 2024 Jan 15:10:1305086. doi: 10.3389/fnut.2023.1305086. eCollection 2023.

Authors

Sebastiaan C de Graaf^{1

2}, Albert Bondt^{1

2}, Danique M H van Rijswijck^{1

2}, Hannah G Juncker^{3

4}, Sien J Mulleners³, Mirjam J A Damen^{1

2}, Max Hoek^{1

2}, Britt J van Keulen³, Johannes B van Goudoever³, Albert J R Heck^{1

2}, Kelly A Dingess^{1

2

3}

Affiliations

¹ Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht, Netherlands.
² Netherlands Proteomics Center, Utrecht, Netherlands.
³ Department of Pediatrics, Amsterdam Reproduction and Development Research Institute, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
⁴ Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, Amsterdam, Netherlands.

Abstract

Introduction: Upon vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) humans will start to produce antibodies targeting virus specific antigens that will end up in circulation. In lactating women such antibodies will also end up in breastmilk, primarily in the form of secretory immunoglobulin A1 (SIgA1), the most abundant immunoglobulin (Ig) in human milk. Here we set out to investigate the SIgA1 clonal repertoire response to repeated SARS-CoV-2 vaccination, using a LC-MS fragment antigen-binding (Fab) clonal profiling approach.

Methods: We analyzed the breastmilk of six donors from a larger cohort of 109 lactating mothers who received one of three commonly used SARS-CoV-2 vaccines. We quantitatively monitored the SIgA1 Fab clonal profile over 16 timepoints, from just prior to the first vaccination until 15 days after the second vaccination.

Results: In all donors, we detected a population of 89-191 vaccine induced clones. These populations were unique to each donor and heterogeneous with respect to individual clonal concentrations, total clonal titer, and population size. The vaccine induced clones were dominated by persistent clones (68%) which came up after the first vaccination and were retained or reoccurred after the second vaccination. However, we also observe transient SIgA1 clones (16%) which dissipated before the second vaccination, and vaccine induced clones which uniquely emerged only after the second vaccination (16%). These distinct populations were observed in all analyzed donors, regardless of the administered vaccine.

Discussion: Our findings suggest that while individual donors have highly unique human milk SIgA1 clonal profiles and a highly personalized SIgA1 response to SARS-CoV-2 vaccination, there are also commonalities in vaccine induced responses.

Keywords: COVID-19; antigen binding fragment; human milk; immunoglobulin A; mass spectrometry.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research received funding through the Netherlands Organization for Scientific Research (NWO) TTW project 15575 (SG and AH), the ENPPS.LIFT.019.001 project (AH) and the Roadmap Program X-omics 184.034.019 (AH). This research received further support by Stichting Steun Emma Kinderziekenhuis. JBvG acknowledges the Amsterdam Infection and Immunity Institute for funding this work through the COVID-19 grant (24175). KD acknowledges the Amsterdam Reproduction and Development Institute for funding this work though the AR&D grant (V.000296).