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Nucleic acid vaccine candidates encapsulated with mesoporous silica nanoparticles against MERS-CoV
Iman Almansour1, B Rabindran Jermy2
1Nucleic Acid Vaccine Laboratory, Department of Epidemic Diseases Research, Institute for Research and Medical Consultations IRMC, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
Abstract:
Middle East respiratory coronavirus (MERS-CoV) is a newly emergent, highly pathogenic coronavirus that is associated with 34% mortality rate. MERS-CoV remains listed as priority pathogen by the WHO. Since its discovery in 2012 and despite the efforts to develop coronaviruses vaccines to fight against SARS-CoV-2, there are currently no MERS-CoV vaccine that has been approved. Therefore, there is high demand to continue on the development of prophylactic vaccines against MERS-CoV. Current advancements in vaccine developments can be adapted for the development of improved MERS-CoV vaccines candidates. Nucleic acid-based vaccines, including pDNA and mRNA, are relatively new class of vaccine platforms. In this work, we developed pDNA and mRNA vaccine candidates expressing S.FL gene of MERS-CoV. Further, we synthesized a silane functionalized hierarchical aluminosilicate to encapsulate each vaccine candidates. We tested the nucleic acid vaccine candidates in mice and evaluated humoral antibodies response. Interestingly, we determined that the non-encapsulated, codon optimized S.FL pDNA vaccine candidate elicited the highest level of antibody responses against S.FL and S1 of MERS-CoV. Encapsulation of mRNA with nanoporous aluminosilicate increased the humoral antibody responses, whereas encapsulation of pDNA did not. These findings suggests that MERS-CoV S.FL pDNA vaccine candidate induced the highest level of humoral responses. This study will enhance further optimization of nanosilica as potential carrier for mRNA vaccines. In conclusion, this study suggests MERS-CoV pDNA vaccine candidate as a suitable vaccine platform for further pivotal preclinical testings.
Insights
The study developed DNA and mRNA vaccines against Middle East respiratory coronavirus (MERS-CoV). The non-encapsulated DNA vaccine candidate showed the highest antibody response, suggesting its potential for MERS-CoV vaccine development.
Area of Science:
- Vaccinology
- Virology
- Nanotechnology
Background:
- Middle East respiratory coronavirus (MERS-CoV) is a highly pathogenic virus with a significant mortality rate, posing a global health threat.
- No approved MERS-CoV vaccines are currently available, highlighting an urgent need for effective vaccine candidates.
- Nucleic acid-based vaccines (pDNA and mRNA) represent promising platforms for rapid vaccine development.
Purpose of the Study:
- To develop and evaluate pDNA and mRNA vaccine candidates expressing the MERS-CoV S.FL gene.
- To investigate the effect of silane-functionalized hierarchical aluminosilicate encapsulation on vaccine efficacy.
- To assess the humoral immune response elicited by the developed MERS-CoV vaccine candidates in a mouse model.
Main Methods:
- Development of pDNA and mRNA vaccine candidates encoding the MERS-CoV S.FL gene.
- Synthesis of silane-functionalized hierarchical aluminosilicate nanoparticles for vaccine encapsulation.
- Immunization of mice with encapsulated and non-encapsulated vaccine candidates.
- Evaluation of humoral antibody responses against MERS-CoV S.FL and S1 antigens.
Main Results:
- The non-encapsulated, codon-optimized S.FL pDNA vaccine candidate induced the highest antibody responses against MERS-CoV S.FL and S1.
- Encapsulation of mRNA with nanoporous aluminosilicate enhanced humoral antibody responses.
- Encapsulation of pDNA with the same nanocarrier did not significantly improve antibody responses.
Conclusions:
- The MERS-CoV S.FL pDNA vaccine candidate demonstrated superior immunogenicity and is a promising platform for further preclinical testing.
- Nanosilica carriers show potential for enhancing mRNA vaccine efficacy against MERS-CoV.
- Further optimization of nanocarrier systems is warranted for improving nucleic acid-based vaccine delivery.
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