# Broad anti-sarbecovirus responses elicited by a single administration of mosaic-8 RBD-nanoparticle vaccine prepared using atomic layer deposition

## TL;DR

A new vaccine technology using atomic layer deposition (ALD) can deliver a single dose that acts like multiple doses, improving immune responses against a wide range of SARS-like coronaviruses.

## Contribution

ALD delivery of mosaic-8b RBD-nanoparticles elicits broader and more cross-reactive antibody responses than conventional immunizations.

## Key findings

- ALD-delivered mosaic-8b RBD-nanoparticles improved mismatched binding and neutralization in mice.
- ALD delivery resulted in broader RBD epitope coverage and distinct IgG subclass and FcγR-binding IgG distributions.
- ALD is promising for vaccines against rapidly mutating or diverse pathogens.

## Abstract

Atomic layer deposition (ALD), a new vaccine technology, permits multiple dosing with a single administration by pulsatile release of one or more immunogens. We evaluated ALD delivery of mosaic-8b [60-mer nanoparticles presenting 8 different SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs)] that elicit broadly cross-reactive antibodies and protect against mismatched sarbecoviruses not represented by RBDs on mosaic-8b. Compared with conventional prime-boost immunizations, ALD-delivered mosaic-8b RBD-nanoparticles elicited antibodies in both naive and pre-vaccinated mice with improved mismatched binding and neutralization. Results of the RBD epitope mapping of serum antibodies from ALD-delivered mosaic-8b were consistent with broader coverage of RBD epitopes compared to conventional immunizations, and systems serology revealed distinct IgG subclass and FcγR-binding IgG distributions. These results suggest that ALD is a promising technology for use with mosaic-8b RBD-nanoparticle vaccines to protect against future sarbecovirus spillovers and support applications for ALD vaccine delivery to elicit cross-reactive antibodies against rapidly mutating or diverse pathogens.

•ALD formulations allow multiple vaccine dosing with a single administration•We compared ALD delivery vs. bolus immunizations of a pan-sarbecovirus vaccine•ALD delivery elicited more cross-reactive Abs in naive and pre-vaccinated mice•Results support ALD delivery for vaccines against rapidly mutating pathogens

ALD formulations allow multiple vaccine dosing with a single administration

We compared ALD delivery vs. bolus immunizations of a pan-sarbecovirus vaccine

ALD delivery elicited more cross-reactive Abs in naive and pre-vaccinated mice

Results support ALD delivery for vaccines against rapidly mutating pathogens

Biological sciences; Immunology; Virology; Biotechnology; Nanomaterials