Human in vitro modeling of adjuvant formulations demonstrates enhancement of immune responses to SARS-CoV-2 antigen

Simon Doss-Gollin; Sanya Thomas; Byron Brook; Kimia Abedi; Célia Lebas; Floriane Auderset; Yamile Lugo-Rodriguez; Guzman Sanchez-Schmitz; David J Dowling; Ofer Levy; Simon D van Haren

doi:10.1038/s41541-023-00759-y

Human in vitro modeling of adjuvant formulations demonstrates enhancement of immune responses to SARS-CoV-2 antigen

NPJ Vaccines. 2023 Oct 26;8(1):163. doi: 10.1038/s41541-023-00759-y.

Authors

Simon Doss-Gollin^#¹, Sanya Thomas^#^{1

2}, Byron Brook^{1

2}, Kimia Abedi¹, Célia Lebas³, Floriane Auderset³, Yamile Lugo-Rodriguez¹, Guzman Sanchez-Schmitz^{1

2}, David J Dowling^{1

2}, Ofer Levy^{1

2

4}, Simon D van Haren^{5

6}

Affiliations

¹ Precision Vaccines Program, Boston Children's Hospital, Boston, MA, 02115, USA.
² Harvard Medical School, Boston, MA, 02115, USA.
³ Vaccine Formulation Institute, 1228 Plan-les-Ouates, Geneva, Switzerland.
⁴ Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
⁵ Precision Vaccines Program, Boston Children's Hospital, Boston, MA, 02115, USA. simon.vanharen@childrens.harvard.edu.
⁶ Harvard Medical School, Boston, MA, 02115, USA. simon.vanharen@childrens.harvard.edu.

^# Contributed equally.

Abstract

Adjuvants can enhance vaccine immunogenicity, but their mechanism of action is often incompletely understood, hampering rapid applicability for pandemic vaccines. Herein, we characterized the cellular and molecular activity of adjuvant formulations available for pre-clinical evaluation, including several developed for global open access. We applied four complementary human in vitro platforms to assess individual and combined adjuvants in unformulated, oil-in-water, and liposomal delivery platforms. Liposomal co-formulation of MPLA and QS-21 was most potent in promoting dendritic cell maturation, selective production of Th1-polarizing cytokines, and activation of SARS-CoV-2 Spike-specific CD4⁺ and CD8⁺ T cells in a co-culture assay. Select formulations also significantly enhanced Spike antigen-specific humoral immunity in vivo. This study confirms the utility of the cumulative use of human in vitro tools to predict adjuvanticity potential. Thus, human in vitro modeling may advance public health by accelerating the development of affordable and scalable adjuvants for vaccines tailored to vulnerable populations.

Abstract

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