Trained immunity induction by the inactivated mucosal vaccine MV130 protects against experimental viral respiratory...

Area of Science:

• Immunology
• Vaccinology
• Infectious Diseases

Background:

• Recurrent respiratory infections pose a significant health burden.
• The mechanism of action for the inactivated polybacterial mucosal vaccine MV130 is not well understood.
• Understanding vaccine-induced immune responses is crucial for developing effective therapies.

Purpose of the Study:

• To elucidate the mechanism of protection conferred by intranasal MV130 against viral respiratory infections.
• To investigate whether MV130-induced protection relies on innate or adaptive immunity.
• To explore the role of trained immunity in MV130's protective effects.

Main Methods:

• Intranasal administration of MV130 in mouse models.
• Assessment of protection against viral (influenza A) and fungal (Candida) infections.
• Pharmacological inhibition of trained immunity using metformin.
• Analysis of immune cell reprogramming (bone marrow progenitors, monocytes) and cytokine production.
• Evaluation in both wild-type and lymphocyte-deficient mice.

Main Results:

• Intranasal MV130 provided long-term heterologous protection against viral respiratory infections in mice.
• Protection against systemic candidiasis was observed in lymphocyte-deficient mice, indicating innate immune involvement.
• Metformin treatment abrogated MV130's protective effect against influenza A virus.
• MV130 induced metabolic reprogramming and enhanced cytokine production in immune progenitor cells and monocytes.

Conclusions:

• Intranasal administration of the inactivated polybacterial vaccine MV130 induces trained immunity.
• This trained immunity mechanism mediates protection against viral respiratory infections.
• MV130's action involves metabolic shifts in immune cells, leading to enhanced cytokine responses and long-term protection.