Identifying Mechanistic Correlates Of Protection Against Pseudomonas Aeruginosa In An Acute Lung Pneumonia Model

Abstract Pseudomonas aeruginosa (Pa) is an opportunistic Gram-negative pathogen that can lead to life-threatening pulmonary infections. Several promising vaccine candidates against Pa evaluated in clinical trials. However, there is still no commercial vaccine available against this pathogen, in part due to a lack of clarity of protective correlates of vaccine–induced immunity. To elucidate correlates of protection against Pa, we used an intranasal whole–cell Pa vaccine adjuvanted with curdlan WCV in a murine vaccination and challenge model. Immunization with WCV significantly decreased the bacterial burden and lung edema after Pa challenge. We found that WCV immunization leads to a significant increase in Th17 cellular immune response and Pa–specific serum IgG and IgA titers compared to naive animals. To identify mechanistic correlates of protection, we performed anti–CD4, – CD8, and –CD20 antibody mediated depletions prior to vaccination and challenge. Depletion of these populations did not affect the response to challenge in naive animals. Interestingly, we observed that depletion of B cells but not CD8+ or CD4+ T cells during WCV priming resulted in loss of protection against Pa. Furthermore, passive immunization of WCV sera was sufficient to protect naive mice against Pa. Taken together, vaccine-mediated humoral immune response was the critical component of immunity against Pa in acute lung pneumonia model. This study suggests that adjuvants stimulating humoral immune response may be used to enhance the efficacy of vaccine candidates against Pa.