Lipopolysaccharide Inhibits FI-RSV Vaccine-enhanced Inflammation Through Regulating Th Responses

Area of Science:

• Immunology
• Vaccinology
• Respiratory Medicine

Background:

• Respiratory syncytial virus (RSV) infection is a leading cause of infant respiratory illness.
• Formalin-inactivated RSV (FI-RSV) vaccines have historically led to enhanced respiratory disease (ERD) in infants, posing a significant challenge for vaccine development.
• Uncontrolled T-helper (Th) immune responses are implicated in ERD pathogenesis.

Purpose of the Study:

• To investigate the potential of lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) agonist, as an adjuvant to mitigate ERD induced by FI-RSV.
• To elucidate the immunomodulatory mechanisms of LPS in the context of FI-RSV vaccination and subsequent RSV challenge.

Main Methods:

• Mice were immunized with FI-RSV and treated with LPS, Pam3Cys (TLR1/2 agonist), or Poly(I:C) (TLR3 agonist).
• Mice were subsequently challenged with RSV to assess lung inflammation, mucus production, inflammatory cell infiltration, and cytokine profiles.
• Antibody production (IgG, IgG2a) was measured to evaluate protective immunity.

Main Results:

• LPS treatment significantly inhibited FI-RSV-enhanced lung inflammation, mucus, inflammatory cell infiltration, and pro-inflammatory cytokines following RSV challenge.
• LPS modulated Th immune responses by suppressing Th2 and Th17 cytokines without increasing Th1 cytokines, indicating a controlled immune response.
• LPS promoted protective IgG and IgG2a antibody production, unlike other TLR agonists tested (Pam3Cys, Poly(I:C)).

Conclusions:

• LPS acts as an effective adjuvant for FI-RSV, inhibiting ERD by regulating Th immune responses.
• LPS demonstrates a favorable safety profile by mitigating ERD without compromising protective antibody production against RSV.
• These findings suggest LPS holds promise for developing safer and more effective RSV vaccines.