Cell reportsMay 2, 2026

mRNA vaccines targeting diverse sarbecovirus spike regions produce unique antibody patterns

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated May 3, 2026

Abstract

Protein-based mosaic-8 nanoparticles induced broadly cross-reactive antibodies, while mRNA-encoded versions may enhance immune responses further.

mRNA-encoded mosaic-8 induced equivalent or enhanced antibody breadth compared to protein-based mosaic-8.
Neutralization potency and targeting of conserved epitopes were improved with mRNA-encoded constructs.
mRNA platforms elicited stronger T cell responses and more balanced IgG subclass profiles.
Distinct epitope signatures were observed across different vaccine types, indicating that antigen display mode influences immune recognition.
The successful adaptation of a multivalent protein vaccine to mRNA could inform future vaccine designs.

Simplified

Protein-based mosaic-8 nanoparticles displaying eight SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) elicited broadly cross-reactive antibodies that could protect from zoonotic spillovers. Here, we extend the mosaic-8 concept to mRNA by encoding membrane-bound RBD quartets (four linked RBDs) as dual quartet RBD-mRNA and dual quartet RBD-EABR-mRNA, the latter leveraging ESCRT- and ALIX-binding region (EABR) technology for display on cell surfaces and secreted virus-like particles. Compared with protein-based mosaic-8, mRNA-encoded mosaic-8 induced equivalent or enhanced antibody breadth, neutralization potencies, and conserved epitope targeting, while eliciting enhanced T cell responses and more balanced IgG subclass profiles consistent with potentially superior Fc effector functions. Finally, systems serology-polyclonal epitope mapping (SySPEM) revealed distinct IgG-subclass-specific epitope signatures across mRNA, EABR-mRNA, and protein vaccines, demonstrating that the mode of antigen display can shape epitope recognition. Successful conversion of a multivalent protein vaccine to mRNA platforms informs the design of broadly protective vaccines and advances mosaic-8 toward clinical development.

Full Text

Full text is available at the source.

View Full Text ↗

Funding

Competing interests

Declaration of interests P.J.B. and A.A.C. are inventors on a US patent application (17/523,813) filed by the California Institute of Technology that covers mosaic RBD-NPs. M.A.G.H. and P.J.B. are inventors on a patent application (US17/835,751; international: PCT/US2022/032702) filed by the California Institute of Technology that covers the EABR technology. M.R.H. is an inventor on patents on spontaneous amide bond formation (EP2534484 and UK Intellectual Property Office 1706430.4) and is a co-founder and shareholder of SpyBiotech. P.J.B., M.A.G.H., A.A.C., J.R.K., K.-M.A.D., R.A.H., and M.R.H. are co-inventors on a provisional US patent application filed by the California Institute of Technology that covers dual quartet mRNA immunogens. P.J.B. is a scientific advisor for Vaccine Company, Inc. M.A.G.H. is a scientific consultant for Vaccine Company, Inc. W.J.M. and P.J.C.L. are employees of Acuitas Therapeutics, a company developing LNP delivery technology; P.J.C.L. holds equity in Acuitas Therapeutics.

PubMed

mRNA vaccines targeting diverse sarbecovirus spike regions produce unique antibody patterns

Abstract

Full Text

Funding

Competing interests

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the mrna technology brief