Abstract
Pseudomonas aeruginosa is an opportunistic pathogen causing acute and chronic respiratory infections associated with morbidity and mortality, especially in patients with cystic fibrosis. Vaccination against P. aeruginosa before colonization may be a solution against these infections and improve the quality of life of at-risk patients. To develop a vaccine against P. aeruginosa, we formulated a novel peptide-based P. aeruginosa subunit vaccine based on the extracellular regions of one of its major siderophore receptors, FpvA. We evaluated the effectiveness and immunogenicity of the FpvA peptides conjugated to keyhole limpet hemocyanin (KLH) with the adjuvant curdlan in a murine vaccination and challenge model. Immunization with the FpvA-KLH vaccine decreased the bacterial burden and lung edema after P. aeruginosa challenge. Vaccination with FpvA-KLH lead to antigen-specific IgG and IgM antibodies in sera, and IgA antibodies in lung supernatant. FpvA-KLH immunized mice had an increase in recruitment of CD11b+ dendritic cells as well as resident memory CD4+ T cells in the lungs compared to non-vaccinated challenged mice. Splenocytes isolated from vaccinated animals showed that the FpvA-KLH vaccine with the adjuvant curdlan induces antigen-specific IL-17 production and leads to a Th17 type of immune response. These results indicate that the intranasal FpvA-KLH conjugate vaccine can elicit both mucosal and systemic immune responses. These observations suggest that the intranasal peptide-based FpvA-KLH conjugate vaccine with curdlan is a potential vaccine candidate against P. aeruginosa pneumonia.
Highlights
Pseudomonas aeruginosa is one of the leading opportunistic Gram-negative pathogens responsible for life-threatening respiratory infections [1]
To develop a vaccine against P. aeruginosa using the outer-membrane proteins (OMPs) FpvA, we designed and selected peptides based on the outer-membrane regions of the protein
We observed that mice immunized with the FpvA-keyhole limpet hemocyanin (KLH) vaccine resulted in significant increase in anti-FpvA peptide-specific IgG compared to unconjugated FpvA
Summary
Pseudomonas aeruginosa is one of the leading opportunistic Gram-negative pathogens responsible for life-threatening respiratory infections [1]. Chronic obstructive pulmonary disease, cystic fibrosis (CF), or those who receive immunosuppressive therapies are susceptible to P. aeruginosa infections [1]. P. aeruginosa-associated chronic lung infections are one of the main contributors to loss of pulmonary function, which is the primary cause of death in patients with CF [3, 4]. Eradication is possible early in life, once the airway of a CF patient becomes chronically colonized, it is difficult to treat P. aeruginosa infections [5]. Therapies that prevent or delay the colonization of P. aeruginosa in CF airways have the potential to increase pulmonary function, and improve the longevity and quality of a CF patient’s life. An effective vaccine against P. aeruginosa could provide a solution against infections caused by this bacterium in CF patients, as well as in other at-risk populations
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