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Inactivated Split MERS-CoV Antigen Prevents Lethal Middle East Respiratory Syndrome Coronavirus Infections in Mice
Heejeong Seo1,2, Yunyueng Jang1, Dongmi Kwak2
1PioneerVaccine, Inc., Chungnam National University, Daejeon 34134, Republic of Korea.
Abstract:
Middle East respiratory syndrome coronavirus (MERS-CoV) causes fatal infections, with about 36% mortality in humans, and is endemic to the Middle East. MERS-CoV uses human dipeptidyl peptidase 4 (hDPP4) as a receptor for infection. Despite continued research efforts, no licensed vaccine is available for protection against this disease in humans. Therefore, this study sought to develop an inactivated fragmented MERS-CoV vaccine grown in Vero cells in an hDPP4-transgenic mouse model. Two-dose immunisation in mice with 15, 20, or 25 μg of spike proteins of inactivated split MERS-CoV antigens induced neutralising antibodies, with titres ranging from NT 80 to 1280. In addition, all immunised mice were completely protected, with no virus detection in tissues, weight loss, or mortality. The immunised splenocytes produced more cytokines that stimulate immune response (IFN-γ and TNF-α) than those that regulate it (IL-4 and IL-10). Taken together, the inactivated fragmented MERS-CoV vaccine is effective for the protection of mice against lethal MERS-CoV. Thus, the inactivated fragmented MERS-CoV vaccine warrants further testing in other hosts.
Insights
An experimental inactivated fragmented MERS-CoV vaccine demonstrated significant protection in mice. This promising vaccine candidate induced neutralizing antibodies and prevented severe disease, warranting further investigation for human use.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Middle East respiratory syndrome coronavirus (MERS-CoV) is a fatal human pathogen endemic to the Middle East.
- MERS-CoV infection has a high mortality rate (approximately 36%) and utilizes human dipeptidyl peptidase 4 (hDPP4) as its cellular receptor.
- Currently, no licensed vaccine is available for human protection against MERS-CoV.
Purpose of the Study:
- To develop and evaluate an inactivated fragmented MERS-CoV vaccine.
- To assess the vaccine's efficacy in a human dipeptidyl peptidase 4 (hDPP4)-transgenic mouse model.
Main Methods:
- An inactivated fragmented MERS-CoV vaccine was produced using Vero cells.
- hDPP4-transgenic mice were immunized with two doses of the vaccine (15, 20, or 25 μg of spike proteins).
- Immune responses, including neutralizing antibody titers and cytokine production (IFN-γ, TNF-α, IL-4, IL-10), were analyzed. Protection was assessed by monitoring virus detection, weight loss, and mortality.
Main Results:
- Immunization with inactivated fragmented MERS-CoV antigens induced neutralizing antibodies with titers ranging from NT 80 to 1280.
- All vaccinated mice exhibited complete protection against lethal MERS-CoV challenge, showing no virus in tissues, weight loss, or mortality.
- Splenocytes from immunized mice showed a heightened production of immune-stimulating cytokines (IFN-γ and TNF-α) compared to immune-regulating cytokines (IL-4 and IL-10).
Conclusions:
- The inactivated fragmented MERS-CoV vaccine is effective in protecting mice against lethal MERS-CoV infection.
- The vaccine elicits a robust immune response characterized by neutralizing antibodies and a favorable cytokine profile.
- This vaccine candidate shows potential and warrants further investigation in other animal models and potentially for human clinical trials.
