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Protocol for Recombinant RBD-based SARS Vaccines: Protein Preparation, Animal Vaccination and Neutralization Detection
Published on: May 2, 2011
Intranasal booster with SARS-CoV-2 RBD protein fused to E. coli enterotoxin a subunit after primary mRNA vaccination
He-Chin Hsieh1, Chung-Chu Chen2, Wen-Chun Liu3
1Institute of Biotechnology, National Tsing Hua University, Hsinchu 30013, Taiwan.
Abstract:
The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 led to the coronavirus infection diseases 2019 (COVID-19) pandemic, significantly impacting global public health and the economy. Numerous COVID-19 vaccines based on the receptor binding domain (RBD) of SARS-CoV-2 spike protein have been developed, utilizing various protein expression platforms and adjuvant systems. In a previous study, we reported using the direct fusion of the A subunit of type IIb E. coli heat-labile enterotoxin with the SARS-CoV-2 RBD protein (RBD-LTA) as an intranasal vaccine candidate (Hsieh et al., 2023). In this study, we investigated the effects of an intranasal booster of RBD-LTA/RBD mixture proteins after one or two doses of intramuscular bivalent BA.4/5 mRNA vaccination over 17 and 35 weeks. Our results indicate that the intranasal RBD-LTA/RBD mixture proteins booster maintains high levels of anti-RBD IgG and neutralizing antibodies, comparable to those elicited by a two-dose mRNA vaccination regimen. An additional RBD-LTA/RBD mixture proteins booster significantly increased antibody titers, demonstrating the potential of this approach for long-term immunity against SARS-CoV-2. Our findings suggest that combining primary mRNA vaccination with an intranasal RBD-LTA/RBD mixture proteins booster can effectively sustain antibody levels over extended periods, providing a promising strategy for long-term protection against SARS-CoV-2 and its variants.
Insights
An intranasal booster of RBD-LTA/RBD mixture proteins, following mRNA vaccination, sustains high antibody levels against SARS-CoV-2. This strategy offers a promising approach for achieving long-term immunity against COVID-19 and its variants.
Area of Science:
- * Immunology
- * Vaccinology
- * Virology
Background:
- * The COVID-19 pandemic, caused by SARS-CoV-2, necessitated the development of effective vaccines.
- * Receptor binding domain (RBD)-based vaccines have shown promise, with various platforms and adjuvants explored.
- * Previous work established RBD-LTA, a fusion protein, as an intranasal vaccine candidate.
Purpose of the Study:
- * To evaluate the impact of an intranasal RBD-LTA/RBD mixture protein booster after mRNA vaccination.
- * To assess the duration of antibody responses at 17 and 35 weeks post-vaccination.
- * To determine the potential for long-term immunity against SARS-CoV-2 variants.
Main Methods:
- * Intramuscular bivalent BA.4/5 mRNA vaccination was administered (one or two doses).
- * An intranasal booster of RBD-LTA/RBD mixture proteins was given.
- * Anti-RBD IgG and neutralizing antibody titers were measured over time.
Main Results:
- * The intranasal booster maintained high levels of anti-RBD IgG and neutralizing antibodies.
- * Antibody titers were comparable to those from a two-dose mRNA regimen.
- * An additional booster significantly increased antibody titers, indicating sustained immune response.
Conclusions:
- * Combining mRNA vaccination with an intranasal RBD-LTA/RBD mixture protein booster effectively sustains antibody levels.
- * This approach shows potential for providing long-term protection against SARS-CoV-2 and its variants.
- * Intranasal boosting offers a promising strategy for durable COVID-19 immunity.
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