Evaluation of mRNA-LNP and adjuvanted protein SARS-CoV-2 vaccines in a maternal antibody mouse model

Ross N England; Elizabeth M Drapeau; Mohamad-Gabriel Alameh; Reihaneh Hosseinzadeh; Drew Weissman; Scott E Hensley

doi:10.1038/s41541-024-00901-4

Evaluation of mRNA-LNP and adjuvanted protein SARS-CoV-2 vaccines in a maternal antibody mouse model

NPJ Vaccines. 2024 Jun 18;9(1):110. doi: 10.1038/s41541-024-00901-4.

Authors

Ross N England^{1

2

3}, Elizabeth M Drapeau¹, Mohamad-Gabriel Alameh⁴, Reihaneh Hosseinzadeh⁵, Drew Weissman³, Scott E Hensley⁶

Affiliations

¹ Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
² Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
³ Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁴ Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁵ Acuitas Therapeutics, Vancouver, BC, Canada.
⁶ Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. hensley@pennmedicine.upenn.edu.

Abstract

Maternal antibodies (matAbs) protect against a myriad of pathogens early in life; however, these antibodies can also inhibit de novo immune responses against some vaccine platforms. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) matAbs are efficiently transferred during pregnancy and protect infants against subsequent SARS-CoV-2 infections. It is unknown if matAbs inhibit immune responses elicited by different types of SARS-CoV-2 vaccines. Here, we established a mouse model to determine if SARS-CoV-2 spike-specific matAbs inhibit immune responses elicited by recombinant protein and nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccines. We found that SARS-CoV-2 mRNA-LNP vaccines elicited robust de novo antibody responses in mouse pups in the presence of matAbs. Recombinant protein vaccines were also able to circumvent the inhibitory effects of matAbs when adjuvants were co-administered. While additional studies need to be completed in humans, our studies raise the possibility that mRNA-LNP-based and adjuvanted protein-based SARS-CoV-2 vaccines have the potential to be effective when delivered very early in life.

Abstract

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