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A Monovalent Mt10-CVB3 Vaccine Prevents CVB4-Accelerated Type 1 Diabetes in NOD Mice
Mahima T Rasquinha1, Ninaad Lasrado1,2, Meghna Sur1
1School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
Abstract:
Enteroviruses, which include Coxsackieviruses, are a common cause of virus infections in humans, and multiple serotypes of the group B Coxsackievirus (CVB) can induce similar diseases. No vaccines are currently available to prevent CVB infections because developing serotype-specific vaccines is not practical. Thus, developing a vaccine that induces protective immune responses for multiple serotypes is desired. In that direction, we created a live-attenuated CVB3 vaccine virus, designated mutant (Mt)10, that offers protection against myocarditis and pancreatitis induced by CVB3 and CVB4 in disease-susceptible A/J mice. Here, we report that the Mt10 vaccine protected against CVB4-triggered type 1 diabetes (T1D) in non-obese diabetic (NOD) mice but the expected subsequent development of spontaneous T1D in these genetically predisposed NOD mice was not altered. We noted that Mt10 vaccine induced significant amounts of neutralizing antibodies, predominantly of the IgG2c isotype, and the virus was not detected in vaccine-challenged animals. Furthermore, monitoring blood glucose levels-and to a lesser extent, insulin antibodies-was found to be helpful in predicting vaccine responses. Taken together, our data suggest that the monovalent Mt10 vaccine has the potential to prevent infections caused by multiple CVB serotypes, as we have demonstrated in various pre-clinical models.
Insights
A novel live-attenuated Coxsackievirus B vaccine (Mt10) shows promise for preventing multiple enterovirus infections. This vaccine effectively protected against CVB-induced myocarditis, pancreatitis, and type 1 diabetes in preclinical models.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Enteroviruses, including Coxsackieviruses, are common human pathogens causing various diseases.
- Multiple Coxsackievirus B serotypes can induce similar illnesses, complicating vaccine development.
- Current lack of broadly protective vaccines necessitates a multivalent approach against Coxsackievirus B infections.
Purpose of the Study:
- To evaluate the efficacy of a live-attenuated Coxsackievirus B3 (CVB3) vaccine candidate, mutant (Mt)10, against multiple CVB serotypes.
- To assess the protective immune response induced by the Mt10 vaccine in preclinical models.
Main Methods:
- Development of a live-attenuated CVB3 vaccine, designated Mt10.
- Challenge studies in A/J mice to assess protection against CVB3 and CVB4-induced myocarditis and pancreatitis.
- Evaluation of Mt10 vaccine efficacy against CVB4-induced type 1 diabetes (T1D) in non-obese diabetic (NOD) mice.
- Monitoring of neutralizing antibody production (IgG2c) and viral detection in vaccinated animals.
- Assessment of blood glucose levels and insulin antibodies as predictors of vaccine response.
Main Results:
- The Mt10 vaccine conferred protection against CVB3 and CVB4-induced myocarditis and pancreatitis in susceptible mice.
- Mt10 vaccination protected NOD mice against CVB4-induced type 1 diabetes, without altering spontaneous T1D development.
- Vaccinated animals developed significant neutralizing antibodies, predominantly IgG2c, and showed no detectable virus.
- Blood glucose and insulin antibody levels correlated with vaccine response.
Conclusions:
- The monovalent Mt10 vaccine demonstrates potential for cross-protection against multiple Coxsackievirus B serotypes.
- Mt10 induces robust neutralizing antibody responses, suggesting its suitability as a broad-spectrum enterovirus vaccine candidate.
- Further preclinical validation supports the development of Mt10 for preventing diverse CVB-associated diseases.
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