Generation of protective immune responses against coxsackievirus B3 challenge by DNA prime-protein boost vaccination

Area of Science:

• Virology
• Immunology
• Vaccinology

Background:

• Coxsackievirus B3 (CVB3) is a significant cause of viral myocarditis and dilated cardiomyopathy.
• Currently, no effective vaccine is available for clinical use against CVB3.
• Developing a vaccine is crucial to prevent CVB3-induced cardiac disease.

Purpose of the Study:

• To evaluate the efficacy of three distinct immunization strategies against CVB3 infection in a mouse model.
• To compare the protective effects of DNA vaccine, protein vaccine, and a combination DNA prime-protein boost strategy.

Main Methods:

• Mice were immunized with a DNA vaccine (VP1 gene), a purified VP1 protein vaccine, or a DNA prime-protein boost vaccine.
• Following immunization, mice were challenged with CVB3.
• Humoral (antibody) and cell-mediated (cytotoxic T cell) immune responses were assessed.
• Viral load, myocarditis severity (myonecrosis, immune cell infiltration), and survival rates were evaluated.

Main Results:

• The DNA prime-protein boost strategy significantly enhanced CVB3-specific antibodies and neutralizing antibodies.
• Virus-specific cytotoxic activity of spleen cells was notably elicited by the prime-boost regimen.
• The DNA prime-protein boost vaccine conferred 75% protection against lethal CVB3 challenge.
• A significant reduction in viral load, myonecrosis, and myocardial immune cell infiltration was observed in surviving mice.

Conclusions:

• The DNA prime-protein boost immunization strategy is superior to DNA or protein vaccines alone in generating robust humoral and cell-mediated immunity against CVB3.
• This combined immunization approach demonstrates significant protective efficacy against CVB3-induced myocarditis and lethality in mice.
• The DNA prime-protein boost vaccine represents a promising candidate for further development against CVB3 infection.