Dendritic cell-based immunization induces Coccidioides Ag2/PRA-specific immune response

Area of Science:

• Immunology
• Vaccinology
• Mycology

Background:

• Valley Fever, caused by Coccidioides spp., is a serious fungal infection with no effective treatment.
• T cell-mediated immunity is crucial for protection against Coccidioides, highlighting the need for vaccine development.

Purpose of the Study:

• To evaluate a dendritic cell (DC)-based vaccine for its ability to induce Coccidioides antigen-specific immune responses.
• To assess the safety and immunogenicity of a novel DC vaccine (Ag2-DC) in a susceptible mouse model.

Main Methods:

• Primary bone marrow-derived dendritic cells (DCs) were transfected with DNA encoding a Coccidioides protective epitope (Ag2/PRA).
• Mice were intranasally immunized with the Ag2-DC vaccine on two occasions.
• Immune responses, including cytokine production (IFN-γ, IL-4, IL-17) and antibody levels (IgG isotypes), were analyzed in blood, lungs, and lymph nodes.

Main Results:

• The Ag2-DC vaccine was well-tolerated, with no observed signs of sickness or significant changes in lung injury markers.
• Immunization induced Coccidioides-specific T cell responses, evidenced by increased levels of IFN-γ, IL-4, and IL-17 secreting cells in the lungs and lymph nodes.
• A significant increase in serum IgG and its isotypes was detected in mice vaccinated with Ag2-DC.

Conclusions:

• Dendritic cell (DC) immunization effectively stimulates Coccidioides antigen-specific immune responses.
• The developed DC vaccine (Ag2-DC) is safe and immunogenic, demonstrating potential for Valley Fever vaccine development.