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A protein subunit vaccine elicits a balanced immune response that protects against Pseudomonas pulmonary infection

Debaki R Howlader1,2, Sayan Das3, Ti Lu1,2

  • 1Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, 66047, USA.

NPJ Vaccines
|March 15, 2023
PubMed

Insights

A new subunit vaccine candidate (L-PaF) against Pseudomonas aeruginosa (Pa) elicits a protective Th1-Th17 immune response. This balanced response is crucial for preventing severe lung infections and overcoming drug resistance.

Area of Science:

  • Immunology
  • Vaccinology
  • Microbiology

Background:

  • Pseudomonas aeruginosa (Pa) is an opportunistic pathogen causing severe nosocomial infections.
  • Increasing drug resistance and lack of a vaccine pose significant healthcare risks.
  • The SARS-CoV-2 pandemic has exacerbated the threat of Pa infections.

Purpose of the Study:

  • To develop and evaluate a novel subunit vaccine candidate against Pseudomonas aeruginosa.
  • To assess the immunogenicity and protective efficacy of the L-PaF vaccine formulation.
  • To elucidate the immune mechanisms underlying vaccine-induced protection.

Main Methods:

  • Formulation of a subunit vaccine (L-PaF) using type III secretion system proteins and LTA1 in an oil-in-water emulsion with a TLR4 agonist.
  • Intranasal (IN) immunization of mice followed by challenge with P. aeruginosa.
  • Lung mRNA sequencing to analyze immunological pathways.
  • Assessment of immune responses using knockout mice for IL-17 and immunoglobulins.

Main Results:

  • The L-PaF vaccine formulation induced a protective Th1-Th17 immune response.
  • Vaccinated mice exhibited an adaptive immune response post-infection, unlike PBS-vaccinated controls.
  • PBS-vaccinated mice showed rapid inflammation, hypoxia, and high bacterial burden.
  • IL-17 and immunoglobulins were critical for protection against P. aeruginosa infection.

Conclusions:

  • A balanced humoral and cellular immune response is essential for preventing Pseudomonas aeruginosa infection.
  • The developed L-PaF vaccine formulation shows potential for eliciting such a protective response.
  • Further development of this vaccine candidate is warranted to combat P. aeruginosa infections.

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