New vaccine promises broad protection against SARS-CoV-2 and other sarbecoviruses

New vaccine promises broad protection against SARS-CoV-2 and other sarbecoviruses

Scientists at the Georgia Institute of Technology and the University of Wisconsin, USA, have developed a broad-spectrum vaccine that can protect against variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and bat sarbecoviruses.

The study is published in the journalNature communication.

background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the most recently emerged beta coronavirus responsible for the devastating coronavirus disease 2019 (COVID-19) pandemic.

SARS-CoV-2 contains spike glycoprotein on its surface that interacts with the host cell membrane receptor angiotensin-converting enzyme 2 (ACE2) to facilitate viral entry. This makes spike protein a crucial target for vaccine development.

During the pandemic, several vaccines have been developed to curb the transmission of SARS-CoV-2 and its highly mutated variants. The Pfizer-BioNTech bivalent vaccine is one of the updated variant-specific formulations with high protective efficacy against a number of SARS-CoV-2 variants.

In addition to the emergence of a wide range of SARS-CoV-2 variants, an extensive reservoir of ACE2-binding sarbecoviruses has been identified in bats, highlighting the need for the development of pan-sarbecovirus and pan-betacoronavirus vaccines.

In this study, scientists developed bivalent and trivalent vaccine formulations using a spike protein nanoparticle platform and validated these formulations in hamsters.

Vaccine design

The scientists had previously developed a nanoparticle-based vaccine that has multiple copies of the SARS-CoV-2 spike protein and showed high protective effects against SARS-CoV-2 in hamsters. In the current study, they used this spike protein nanoparticle platform to develop a cocktail vaccine against class 1 human ACE2-binding sarbecoviruses with pandemic potential.

They developed a series of nanoparticle platforms, each presenting a single spike protein from different sarbecoviruses (original SARS-CoV-2 spike protein; four Omicron variants BA.1, BA.5, BA.2.75.2, XBB; SARS-CoV-2 spike protein). 1; and bat CoV SHC014). They determined the immunogenicity of these formulations in hamsters.

They analyzed the antigen landscape and selected a bivalent (two prominent spike proteins) formulation and two trivalent (three prominent spike proteins) formulations to characterize their neutralizing antibody responses and protective effects in hamsters infected with SARS-CoV-2 omicron variants (XBB.1 and BA.5) and bat coronaviruses (SHC014 and WIV1).

Validation of vaccine formulations

The scientists immunized hamsters with the bivalent or trivalent vaccine formulations containing Alhydrogel as an adjuvant. They also immunized a separate group of hamsters with the bivalent Pfizer-BioNTech vaccine as a positive control.

Analysis of humoral immune responses revealed that all three formulations were able to effectively induce neutralizing antibody titers against the ancestral SARS-CoV-2 and the Omicron variant BA.5.

Two trivalent vaccines containing an additional Omicron strain resulted in robust neutralizing titers against the latest Omicron variant, XBB.1. However, the bivalent vaccine showed reduced neutralizing effectiveness against the XBB.1 variant.

Regarding bat coronaviruses, all three formulations demonstrated equivalent neutralizing efficacy against SHC014 and WIV1. In contrast, the Pfizer-BioNTech bivalent vaccine failed to induce detectable neutralizing antibody titers against any of the coronaviruses tested.

Two doses of Pfizer vaccine containing 30 micrograms of spike protein are typically used to immunize people. However, only a single immunization with 10 micrograms of spike protein was performed in hamsters. This could explain the lack of neutralizing titers in hamsters immunized with the Pfizer vaccine.

The scientists also tested the protective effects of three vaccine formulations in hamsters infected with the Omicron variants BA.5 and XBB.1 six weeks after immunization. Three days after exposure to the virus, they tested the virus titers in the lungs.

The results showed that all three formulations can provide complete protection against both the BA.5 and XXB.1 variants. No detectable virus titers were observed in the lungs of immunized hamsters.

Although the bivalent formulation produced significantly lower neutralizing titers against XBB.1, it completely protected the hamsters from XBB.1. However, a single immunization with the Pfizer vaccine could not provide complete protection against BA.5 and XBB.1.

The scientists also examined the protective effect of their trivalent formulation against bat coronaviruses. They found that the immunized hamsters had no detectable virus titers in their lungs, indicating complete protection.

ASDS-PAGE characterization of biotinylated S proteins. The unprocessed gel is shown in the supplementary figure.3. This gel was tested twice with the same preparation for each sample, with similar results.bSchematic representation of the binding of various biotinylated S proteins to MS2-SA. (MS2: light gray, PDB 2MS2; SA: dark gray, PDB 3RY2; S: green/orange/purple, PDB 6VSB) (C) SDS-PAGE gel from S and VLP-S for 614D, BA.2.75.2, XBB and SHC014. Each VLP-S was boiled to destroy the streptavidin-biotin conjugation. The unprocessed gel is shown in the supplementary figure.3. This gel was tested twice with the same preparation for each sample, with similar results.DCharacterization of VLP-614D-S (orange), VLP-SHC014-S (green), VLP-BA.2.75.2-S (red) and VLP-XBB-S (cyan) by dynamic light scattering.eCharacterization of binding of ACE2-Fc and S2P6 antibodies to all VLP-S. (Mean ± SD, n = 3: an independent test with three technical replicates). The bar color identifies each VLP-S sample (VLP-614D-S: orange; VLP-BA.1-S: dark blue; VLP-BA.5-S: brown; VLP-XBB-S: cyan; VLP-BA. 2.75.2: red; VLP-SARS-CoV-1-S: purple; VLP-SHC014-S: green; VLP only.FCharacterization of VLP-XBB-S, VLP-614D-S, VLP-BA.2.75.2-S and VLP-SHC014-S by negative stain transmission electron microscopy. Arrowheads ▲ indicate S proteins on the VLP surface, with white arrowheads indicating straight-up spike proteins and red arrowheads indicating tilted spike proteins. For each sample, at least 70 images from a VLP-S preparation were collected and analyzed, with similar results.

Study Importance

The trivalent spike protein nanoparticle formulation developed in the study shows high efficacy in eliciting a broadly neutralizing antibody response against SARS-CoV-1 and SARS-CoV-2-related sarbecoviruses.

Ravi Kane, one of the paper's corresponding authors, explained: "This vaccine may protect not only against the current strain circulating this year, but also against future variants."

This sounds like another mRNA drug disguised under the guise of the newly defined word “vaccine.” “Vaccine” used to mean something different, namely immunity and extensive testing, before the government redefined it to mean anything that said whether it worked or was even safe.

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