Interleukin-12 and protective immunity to schistosomes

Area of Science:

• Immunology
• Vaccinology
• Parasitology

Background:

• The attenuated vaccine against Schistosoma mansoni induces Th1-mediated protective immunity.
• The role of Interleukin-12 (IL-12) in this protective immunity model was investigated.

Purpose of the Study:

• To identify the role of IL-12 in Th1-mediated protective immunity against Schistosoma mansoni.
• To explore the potential of IL-12 as an adjuvant in vaccine development.

Main Methods:

• Measurement of IL-12 (p40 mRNA) levels in lymph nodes and lungs of vaccinated mice.
• Treatment of vaccinated mice with anti-IL-12 antibodies to assess the impact on IFN gamma and IL-4 secretion.
• Immunization with soluble antigens from the lung-stage of the parasite (SLAP) combined with IL-12 as an adjuvant.
• Assessment of protection against reinfection and analysis of T cell responses.
• In vivo ablation of NK cells and genetic disruption of the IFN gamma receptor to elucidate mechanisms.

Main Results:

• Elevated IL-12 levels were detected in vaccinated mice.
• Anti-IL-12 treatment reduced the IFN gamma:IL-4 ratio but only marginally affected resistance.
• SLAP + IL-12 immunization elicited a strong Th1 response with significant protection against reinfection.
• IL-12 directly primes T cells independent of IFN gamma, and NK cells contribute to IFN gamma production.

Conclusions:

• IL-12 is critical for protective immunity against Schistosoma mansoni.
• IL-12, particularly when used with SLAP, can induce a dominant Th1 response and significant protection.
• IL-12 shows promise as an adjuvant for developing an effective vaccine against schistosomiasis.