Modeling memory B cell responses in a lymphoid organ-chip to evaluate mRNA vaccine boosting
Predicting the immunogenicity of candidate vaccines in humans remains a challenge. To address this issue, we developed a lymphoid organ-chip (LO chip) model based on a microfluidic chip seeded with human PBMC at high density within a 3D collagen matrix. Perfusion of the SARS-CoV-2 spike protein mimicked a vaccine boost by inducing a massive amplification of spike-specific memory B cells, plasmablast differentiation, and spike-specific antibody secretion. Features of lymphoid tissue, including the formation of activated CD4+ T cell/B cell clusters and the emigration of matured plasmablasts, were recapitulated in the LO chip. Importantly, myeloid cells were competent at capturing and expressing mRNA vectored by lipid nanoparticles, enabling the assessment of responses to mRNA vaccines. Comparison of on-chip responses to Wuhan monovalent and Wuhan/Omicron bivalent mRNA vaccine boosts showed equivalent induction of Omicron neutralizing antibodies, pointing at immune imprinting as reported in vivo. The LO chip thus represents a versatile platform suited to the preclinical evaluation of vaccine-boosting strategies.
Authors
- Samy Gobaa (ORCID: https://orcid.org/0000-0002-0125-8674)
- Lorna Ewart (ORCID: https://orcid.org/0000-0002-8258-7460)
- Rémy Robinot (ORCID: https://orcid.org/0000-0002-3651-0171)
- Raphaël Jeger‐Madiot
- Bárbara F. Fonseca (ORCID: https://orcid.org/0000-0001-6403-4099)
- Héloïse Mary (ORCID: https://orcid.org/0000-0003-1171-3260)
- Lisa A. Chakrabarti (ORCID: https://orcid.org/0000-0002-1895-3630)
- Delphine Planas (ORCID: https://orcid.org/0000-0002-2509-9954)
- Jérôme Kervevan (ORCID: https://orcid.org/0000-0002-5070-022X)
- Isabelle Staropoli (ORCID: https://orcid.org/0000-0001-8637-4545)
- Olivier Schwartz (ORCID: https://orcid.org/0000-0002-0729-1475)
- Michael Bscheider (ORCID: https://orcid.org/0000-0001-7808-3270)
- Stacy Gellenoncourt (ORCID: https://orcid.org/0000-0003-1896-7212)
- Camilla Collina (ORCID: https://orcid.org/0009-0002-2632-0136)
- Hippolyte Debarnot (ORCID: https://orcid.org/0009-0001-7261-8470)
Institutions
- Roche (Switzerland) (CH)
- Institut Pasteur (FR)
- Université Paris Cité (FR)
- Emulate (United States) (US)
Publication Details
- Journal
- The Journal of Experimental Medicine
- Published
- 2024-09-06
- DOI
- https://doi.org/10.1084/jem.20240289
- Citations
- 24
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 9.34
Funders
- Institut Pasteur
- Fondation de France