Novel Vaccine Candidates Targeting Antibiotic-Resistant A. baumannii and P. aeruginosa in an Acute Pneumonia Model

Nouran Rezk (University College Dublin, Ireland)

10:45 - 11:00 Tuesday 14 April Morning

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Abstract

Acinetobacter baumannii and Pseudomonas aeruginosa are antibiotic-resistant pathogens causing life-threatening hospital-acquired infections. Classified by the World Health Organization (WHO) as "critical" and "high" priority pathogens, respectively, they urgently require novel treatments. Although vaccines show promise in combating infections, no licensed vaccines are available. We have identified 12 novel proteins involved in the attachment of P. aeruginosa or A. baumannii to human lung epithelial cells; some of which share homology between both pathogens. This study evaluates the protective efficacy of homologous AgN antigens from both pathogens, with a view to the development of a broadly protective vaccine against these opportunistic nosocomial infections. Mice immunised with SAS-adjuvanted P. aeruginosa AgN and subsequently challenged in an acute P. aeruginosa pneumonia model showed a significant reduction in bacterial lung colonisation (0.96-log10, p=0.0268) and robust total IgG, IgG1, and IgG2a antibody titres (1: 312,500, 1: 1,562,500, and 1: 12,500, respectively).  Mice immunised with SAS-adjuvanted A. baumannii AgN and challenged in an acute A. baumannii pneumonia model exhibited significant reductions in bacterial lung colonisation (0.74-log10 CFU, p<0.0102) and spleen dissemination (0.9-log10, p<0.0426), along with high total IgG and IgG1 antibody titres (1: 62,500 and 1:78,125, respectively). ELISpot analysis revealed that both P. aeruginosa and A. baumannii rAgN antigens elicited substantial IFN-γ (6.4-fold, p=0.007, and 4-fold, p=0.0035, respectively) and IL-17 responses (9.2-fold, p<0.0001 and 5.8-fold, p=0.0286, respectively) compared to adjuvant-only control, suggesting Th1 and Th17 cellular responses contribute to protection. These novel antigens represent promising candidates for a multivalent vaccine against antibiotic-resistant P. aeruginosa and A. baumannii.

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