Vaccine strategies against bacterial pathogens in cystic fibrosis patients

Moigne, Vincent Le; Gaillard, Jean‐Louis; Herrmann, Jean-Louis

doi:10.1016/j.medmal.2015.11.013

Cited by 10 publications

(8 citation statements)

References 63 publications

(62 reference statements)

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“…However, with the recent failure of the IC43 vaccine in a phase II clinical trial (11), there are currently no approved vaccines against P. aeruginosa or vaccines in advanced stages of clinical development (12). Renewal of the P.…”

Section: Introductionmentioning

confidence: 99%

A Live Salmonella Vaccine Delivering PcrV through the Type III Secretion System Protects against Pseudomonas aeruginosa

Aguilera-Herce

García-Quintanilla

Romero-Flores

et al. 2019

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Pseudomonas aeruginosa is a common Gram-negative opportunistic pathogen that is intrinsically resistant to a wide range of antibiotics. The development of a broadly protective vaccine against P. aeruginosa remains a major challenge. Here, we used an attenuated strain of Salmonella enterica serovar Typhimurium as a vehicle to express P. aeruginosa antigens. A fusion between the S. enterica type III secretion effector protein SseJ and the P. aeruginosa antigen PcrV expressed under the control of the sseA promoter was translocated by Salmonella into host cells in vitro and elicited the generation of specific antibodies in mice. Mice immunized with attenuated Salmonella expressing this fusion had reduced bacterial loads in the spleens and lungs and lower serum levels of proinflammatory cytokines than control mice after P. aeruginosa infection. Importantly, immunized mice also showed significantly enhanced survival in this model. These results suggest that type III secretion effectors of S. enterica are appropriate carriers in the design of a live vaccine to prevent infections caused by P. aeruginosa. IMPORTANCE The Gram-negative bacterium Pseudomonas aeruginosa is an important opportunistic pathogen that causes infections in cystic fibrosis and hospitalized patients. Therapeutic treatments are limited due to the emergence and spread of new antibiotic-resistant strains. In this context, the development of a vaccine is a priority. Here, we used an attenuated strain of Salmonella enterica serovar Typhimurium as a vehicle to express and deliver the Pseudomonas antigen PcrV. This vaccine induced the generation of specific antibodies in mice and protected them from lethal infections with P. aeruginosa. This is an important step toward the development of an effective vaccine for the prevention of infections caused by P. aeruginosa in humans.

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Section: Introductionmentioning

confidence: 99%

A Live Salmonella Vaccine Delivering PcrV through the Type III Secretion System Protects against Pseudomonas aeruginosa

Aguilera-Herce

García-Quintanilla

Romero-Flores

et al. 2019

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“…Vaccination strategies to prevent P. aeruginosa infection have attracted a great deal of attention. In the past two decades, a number of different vaccines and several monoclonal antibodies have been developed for active and passive vaccination against P. aeruginosa infection ( Pier, 2005 ; Priebe and Goldberg, 2014 ; Vincent, 2014 ; Grimwood et al, 2015 ; Le Moigne et al, 2016 ). The antigens used in these studies include lipopolysaccharides ( Pier, 2007 ), surface polysaccharides ( Pier, 2000 ), outer membrane proteins ( Gao et al, 2017 ; Rello et al, 2017 ), secreted proteins ( Hamaoka et al, 2017 ; Yang et al, 2017 ), flagella ( Hassan et al, 2017 ), and pili ( Ohama et al, 2006 ; Banadkoki et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

“…The antigens used in these studies include lipopolysaccharides ( Pier, 2007 ), surface polysaccharides ( Pier, 2000 ), outer membrane proteins ( Gao et al, 2017 ; Rello et al, 2017 ), secreted proteins ( Hamaoka et al, 2017 ; Yang et al, 2017 ), flagella ( Hassan et al, 2017 ), and pili ( Ohama et al, 2006 ; Banadkoki et al, 2016 ). Several vaccine candidates even entered phase II/III clinical trials ( Baumann et al, 2004 ; Pier, 2005 ; Sharma et al, 2011 ; Le Moigne et al, 2016 ; Rello et al, 2017 ). However, these efforts have not resulted in a marketable product to date, which can be attributed to two primary reasons.…”

Section: Introductionmentioning

confidence: 99%

PA0833 Is an OmpA C-Like Protein That Confers Protection Against Pseudomonas aeruginosa Infection

Yang

Zou

et al. 2018

Front. Microbiol.

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Pseudomonas aeruginosa is a formidable pathogen that causes infections with high mortality rates. Because of its ability to form biofilms and rapidly acquire resistance to many first-line antibiotics, P. aeruginosa-related infections are typically difficult to cure by traditional antibiotic treatment regimes. Thus, new strategies to prevent and treat such infections are urgently required. PA0833 is a newly identified protective antigen of P. aeruginosa that was identified in a screen using a reverse vaccine strategy in our laboratory. In this study, we further confirmed its protective efficacy in murine sepsis and pneumonia models. Immunization with PA0833 induced strong immune responses and resulted in reduced bacterial loads; decreased pathology, inflammatory cytokine expression and inflammatory cell infiltration; and improved survival. Furthermore, PA0833 was identified as an OmpA C-like protein by bioinformatics analysis and biochemical characterization and shown to contribute to bacterial environmental stress resistance and virulence. These results demonstrate that PA0833 is an OmpA C-like protein that induces a protective immune response in mice, indicating that PA0833 is a promising antigen for vaccine development.

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“…Особенностью возбудителя является высокая устойчивость к различным факторам внешней среды и способность быстро вырабатывать устойчивость к применяемым антибактериальным препаратам [6,11,13]. Поэтому исследователи разных стран осуществляют разработку иммунобиологических лекарственных средств, предназначенных для решения проблемы синегнойной инфекции [1,9,10]. В ФГБНУ НИИВС имени И. И. Мечникова проводятся исследования с целью создания рекомбинантной вакцины для профилактики синегнойной инфекции.…”

Section: Preclinical Studies Of Recombinant Pseudomonas Vaccineunclassified

Preclinical Studies of Recombinant Pseudomonas Vaccine

Mihailova

Kaloshin

Зимина

et al. 2018

Journal of microbiology, epidemiology and immunobiology

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Aim. Evaluation of the efficacy and safety of the three experimental lots of Recombinant Pseudomonas Vaccine. Materials and methods. The preparation contained the recombinant proteins OprF and toxoid that were purified by chromatography in nickel-sepharose. Aluminum hydroxide was used as an adjuvant. The authenticity of the vaccine components was confirmed by electrophoresis and immunoblotting. The concentration of endotoxin in the vaccine was determined by LAL test. The abnormal toxicity was evaluated in mice and cavy. The anaphylactic activity was evaluated in cavy. The delayed-type hypersensitivity reaction was evaluated in mice. Evaluation of the immunogenicity was carried out in an experiment with on double immunization of mice with following intraperitoneally infection by a live virulent culture of P. aeruginosa (PA-103 strain). Results. The authenticity of the vaccine, sterility, non-pyrogenicity and non-toxicity were confirmed after the studying of the quality indicators of the three lots of Recombinant Pseudomonas Vaccine. In animal experiments, the vaccine did not possess allergic properties and it was shown that it protected mice against Pseudomonas infection with Index of efficiency 3.0 and more. Conclusion. The efficacy, the safety, and the standardization of three experimental lots of the recombinant vaccine, which is intended to prevent infections caused by P. aeruginosa, have been shown.

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Vaccine strategies against bacterial pathogens in cystic fibrosis patients

Cited by 10 publications

References 63 publications

A Live Salmonella Vaccine Delivering PcrV through the Type III Secretion System Protects against Pseudomonas aeruginosa

A Live Salmonella Vaccine Delivering PcrV through the Type III Secretion System Protects against Pseudomonas aeruginosa

PA0833 Is an OmpA C-Like Protein That Confers Protection Against Pseudomonas aeruginosa Infection

Preclinical Studies of Recombinant Pseudomonas Vaccine

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