Innovative Nanoparticle Vaccine Design for Broad Protection Against Sarbecoviruses

A groundbreaking experimental vaccine, developed by leading researchers, holds promise in providing protection against emerging variants of SARS-CoV-2 and related coronaviruses known as sarbecoviruses, which have the potential to transition from animals to humans.

Understanding Sarbecoviruses and Their Risks

Sarbecoviruses encompass not only SARS-CoV-2, the causative agent of COVID-19, but also the virus responsible for the initial SARS outbreak in the early 2000s. Currently circulating sarbecoviruses in bats and other mammals may also pose a future risk to human health.

The innovative vaccine utilizes nanoparticles designed to carry up to eight distinct versions of sarbecovirus receptor-binding proteins (RBDs). By targeting RBD regions that remain largely unchanged across various strains of these viruses, this approach makes it significantly harder for the viruses to evolve and evade vaccine-induced immunity.

Innovative Nanoparticle Design for Broad Protection

“This research exemplifies the successful integration of computational methods with immunological experimentation,” states a prominent professor involved in the study. The research findings are published in the esteemed journal Cell, with contributions from a team of talented researchers, including graduate students and postdoctoral fellows.

The study builds upon earlier work that introduced a unique “mosaic” 60-mer nanoparticle displaying eight different sarbecovirus RBD proteins. The RBD is critical for viral entry into host cells and is the primary target for antibodies against sarbecoviruses.

Targeting conserved RBD areas makes it significantly harder for viruses to escape vaccine-induced immunity.

While some RBD regions are prone to mutations, leading to challenges in vaccine efficacy, the aim is to develop a vaccine that encourages the production of antibodies targeting the conserved areas of the RBDs that are less likely to change. This could offer extensive protection against multiple sarbecovirus strains.

Preclinical Success and Next Steps

The researchers designed a nanoparticle that presents 60 copies of RBDs from eight related sarbecoviruses, thus ensuring that each nanoparticle displays a diverse array of RBDs. This arrangement increases the likelihood of activating B cells that can recognize conserved regions, ultimately enhancing the immune response.

Preliminary animal studies demonstrated that this mosaic-8 vaccine elicited robust antibody responses against various strains of SARS-CoV-2 and offered protective benefits against both SARS-CoV-2 and original SARS challenges.

Following earlier studies published in 2021 and 2022, the research team explored computational strategies to optimize RBD combinations for improved antibody responses. By analyzing numerous mutations and naturally occurring RBD proteins from zoonotic sarbecoviruses, they were able to identify promising candidates for further development.

The researchers created multiple nanoparticle vaccines, including mosaic-2COM and mosaic-5COM, which incorporated two or five different RBD proteins. Additionally, they developed mosaic-7COM using seven naturally occurring RBD proteins selected for their variability while retaining conserved regions.

Upon testing these new vaccines in mice, they observed that mosaic-2COM and mosaic-5COM outperformed earlier versions. Notably, mosaic-7COM demonstrated exceptional efficacy, generating antibodies capable of neutralizing several tested viruses, including SARS-CoV-2 variants.

In an effort to simulate real-world scenarios where individuals may have prior exposure to SARS-CoV-2 through infection or vaccination, pre-vaccinated mice consistently showed strong responses when administered mosaic-7COM.

Plans are underway for clinical trials of the mosaic-8 RBD-nanoparticle vaccine, with hopes to advance the even more effective mosaic-7COM into clinical evaluation. The team aims to explore mRNA delivery methods for these vaccines to enhance their manufacturability and accessibility.

This research initiative received substantial funding from various prestigious organizations, including the National Science Foundation, National Institutes of Health, Wellcome Leap, the Bill and Melinda Gates Foundation, and more.