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Protocol for Recombinant RBD-based SARS Vaccines: Protein Preparation, Animal Vaccination and Neutralization Detection
Published on: May 2, 2011
An mRNA vaccine encoding the SARS-CoV-2 Omicron XBB.1.5 receptor-binding domain protects mice from the JN.1 variant
Ryuta Uraki1, Maki Kiso2, Mutsumi Ito3
1The University of Tokyo Pandemic Preparedness, Infection and Advanced Research Center (The UTOPIA Center), Institutes for Advanced Study, University of Tokyo, Tokyo, 108-8639, Japan; International Virus Infectious Disease Research Center, National Institute of Global Health and Medicine, Japan Institute for Health Security, Tokyo, 162-8655, Japan; International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, 162-8655, Japan; Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan.
Background:
The SARS-CoV-2 Omicron BA.2.86 variant and its descendant lineages, including JN.1, are rapidly spreading globally. We developed mRNA encoding the SARS-CoV-2 RBD derived from XBB.1.5 (XBB.1.5-type LNP-mRNA-RBD), in line with WHO recommendations. Many individuals have acquired immunity specific to the ancestral SARS-CoV-2 strain or early Omicron variants, such as BA.1, BA.2, or BA.5, through natural infection and/or vaccination. However, the efficacy of XBB.1.5-type LNP-mRNA-RBD boost vaccination against a clinical isolate of JN.1 remains uncertain.
Methods:
In this study, we used a small amount of LNP-mRNA-RBD as a prime dose compared with a booster shot to mimic the waning immunity against the ancestral and BA.4/5 strains. We immunised female mice with XBB.1.5-type LNP-mRNA-RBD as a booster vaccine and examined the cellular and humoural responses as well as the protective efficacy against a JN.1 variant.
Findings:
We found that immunisation of mice with the XBB.1.5-type LNP-mRNA-RBD as a booster shot induced XBB.1.5-specific neutralising activity and T cell responses. Moreover, immunisation with a bivalent vaccine consisting of the ancestral-type and BA.4/5-type LNP-mRNA-RBD as the primary dose followed by XBB.1.5-type LNP-mRNA-RBD boosting induced enhanced levels of cross-reactive antibodies against the JN.1 strain, compared to using the ancestral-type vaccine as the primary dose. In addition, we found that a booster shot of LNP-mRNA-RBD based on the XBB.1.5 strain reduced the viral burden in the respiratory organs after JN.1 challenge.
Interpretation:
Our findings suggest that XBB.1.5-type LNP-mRNA-RBD is effective against antigenically distinct JN.1 infection.
Funding:
This work was supported by grants from the Japan Program for Infectious Diseases Research and Infrastructure (JP25wm0125002), the Japan Initiative for World-leading Vaccine Research and Development Centers (JP253fa627001), and the Vaccine Development project (JP21nf0101625) from the Japan Agency for Medical Research and Development, and the National Institutes of Allergy and Infectious DiseasesCenter for Research on Influenza Pathogenesis and Transmission (CRIPT) (75N93021C00014).
Insights
A booster vaccine using XBB.1.5-type LNP-mRNA-RBD effectively protected mice against the JN.1 variant. This vaccine strategy induced strong immune responses and reduced viral load in respiratory organs, suggesting its potential against emerging SARS-CoV-2 strains.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- The SARS-CoV-2 Omicron JN.1 variant is spreading globally, raising concerns about vaccine effectiveness.
- Existing immunity from prior infections or vaccinations may not fully protect against new variants.
- The efficacy of current mRNA vaccines against JN.1 requires further investigation.
Purpose of the Study:
- To evaluate the immunogenicity and protective efficacy of an XBB.1.5-type LNP-mRNA-RBD vaccine as a booster against the SARS-CoV-2 JN.1 variant.
- To assess cellular and humoral immune responses following vaccination.
- To determine the impact of different primary vaccination strategies on boosting against JN.1.
Main Methods:
- Mice were immunized with XBB.1.5-type LNP-mRNA-RBD as a booster vaccine.
- Cellular and humoral immune responses were analyzed.
- Protective efficacy was assessed by challenging immunized mice with a JN.1 variant and measuring viral burden in respiratory organs.
Main Results:
- XBB.1.5-type LNP-mRNA-RBD booster vaccination induced specific neutralizing activity and T cell responses against XBB.1.5.
- A bivalent primary vaccine (ancestral + BA.4/5) followed by XBB.1.5 boosting enhanced cross-reactive antibodies against JN.1 compared to ancestral boosting.
- XBB.1.5-based LNP-mRNA-RBD booster vaccination reduced viral burden in respiratory organs after JN.1 challenge.
Conclusions:
- XBB.1.5-type LNP-mRNA-RBD booster vaccination demonstrates effectiveness against the antigenically distinct JN.1 variant.
- The findings support the use of updated mRNA vaccines to combat emerging SARS-CoV-2 strains.
- Optimized primary vaccination strategies can enhance booster responses against novel variants.
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