Protection against Experimental Melioidosis following Immunisation with a Lipopolysaccharide-Protein Conjugate

Scott, Andrew E.; Ngugi, Sarah A.; Laws, Thomas R.; Corser, David; Lonsdale, Claire L.; D’Elia, Riccardo V.; Titball, Richard W.; Williamson, E. Diane; Atkins, Timothy P.; Prior, Joann L.

doi:10.1155/2014/392170

Cited by 27 publications

(24 citation statements)

References 43 publications

(49 reference statements)

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“…However, while the conjugate vaccine broadened the range of antibody isotypes, this candidate did not afford significantly greater protection than the unconjugated mix of free LPS and TetH c formulation (75% survival) [90]. containing Bp LPS, CPS, and protein antigens significantly protected mice against lethal aerosol challenge, with nearly 60% of mice surviving for 2 weeks post-infection [62].…”

Section: Glycoconjugate-based Subunit Vaccines Vaccine Formulations mentioning

confidence: 93%

“…In the case of vaccines containing single proteins or unconjugated LPS, immunity is characterized by Th2-biased responses, which are not thought to be optimally effective against pathogens that can replicate intracellularly, such as Bp or Bm (For example, [89] [90]). Therefore, it is likely that polyvalent vaccines combining several antigens may be more effective in generating complete protective immunity against heterologous strains and diverse routes of infection [91] [4].…”

Section: Subunit Vaccinesmentioning

confidence: 99%

“…conjugated with the Hc fragment of the tetanus toxin (TetH c ) given IP induced notable protection in a lethal IP challenge with Bp, with 81% of mice surviving to 29 days postchallenge, as compared to 62% protection of mice immunized with unconjugated, purified Bp LPS alone [90]. However, while the conjugate vaccine broadened the range of antibody isotypes, this candidate did not afford significantly greater protection than the unconjugated mix of free LPS and TetH c formulation (75% survival) [90].…”

Section: Glycoconjugate-based Subunit Vaccines Vaccine Formulations mentioning

confidence: 99%

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Melioidosis and glanders modulation of the innate immune system: barriers to current and future vaccine approaches

Aschenbroich¹,

Lafontaine²,

Hogan³

2016

Expert Review of Vaccines

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Burkholderia pseudomallei and Burkholderia mallei are pathogenic bacteria causing fatal infections in animals and humans. Both organisms are classified as Tier 1 Select Agents owing to their highly fatal nature, potential/prior use as bioweapons, severity of disease via respiratory exposure, intrinsic resistance to antibiotics, and lack of a current vaccine. Disease manifestations range from acute septicemia to chronic infection, wherein the facultative intracellular lifestyle of these organisms promotes persistence within a broad range of hosts. This ability to thrive intracellularly is thought to be related to exploitation of host immune response signaling pathways. There are currently considerable gaps in our understanding of the molecular strategies employed by these pathogens to modulate these pathways and evade intracellular killing. A better understanding of the specific molecular basis for dysregulation of host immune responses by these organisms will provide a stronger platform to identify novel vaccine targets and develop effective countermeasures.

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Section: Glycoconjugate-based Subunit Vaccines Vaccine Formulations mentioning

confidence: 93%

Section: Subunit Vaccinesmentioning

confidence: 99%

Section: Glycoconjugate-based Subunit Vaccines Vaccine Formulations mentioning

confidence: 99%

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Melioidosis and glanders modulation of the innate immune system: barriers to current and future vaccine approaches

Aschenbroich¹,

Lafontaine²,

Hogan³

2016

Expert Review of Vaccines

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“…Antibody responses directed against the various protein antigens were assessed by ELISA essentially as previously described [27] using 5 g/ml of each protein to coat ELISA wells. A reading of twice background or above was considered positive and the titre was determined to be the reciprocal of the final positive dilution.…”

Section: Igg1 and Igg2a Elisamentioning

confidence: 99%

Immunisation with proteins expressed during chronic murine melioidosis provides enhanced protection against disease

Champion

Gourlay

Scott

et al. 2016

Vaccine

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a b s t r a c tThere is an urgent need for an effective vaccine against human disease caused by Burkholderia pseudomallei, and although a wide range of candidates have been tested in mice none provide high level protection. We considered this might reflect the inability of these vaccine candidates to protect against chronic disease. Using Q-RT PCR we have identified 6 genes which are expressed in bacteria colonising spleens and lungs of chronically infected mice. Three of the genes (BPSL1897, BPSL3369 and BPSL2287) have been expressed in Escherichia coli and the encoded proteins purified. We have also included BPSL2765, a protein known to induce immune responses associated with a reduced incidence of chronic/recurrent disease in humans. Immunisation of mice with a combination of these antigens resulted in the induction of antibody responses against all of the proteins. Compared with mice immunised with capsular polysaccharide or LolC protein, mice immunised with the combination of chronic stage antigens showed enhanced protection against experimental disease in mice.

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“…In fact, previous studies have shown that proteins alone can provide significant, albeit incomplete, protection against Burkholderia challenge (11)(12)(13)(14). However, more recent studies have shown that when immunogenic proteins are incorporated in a glycoconjugate vaccine in conjunction with the highly antigenic Burkholderia lipopolysaccharide (LPS) or capsular polysaccharide (CPS), a more robust immune response is generated (15)(16)(17)(18). Our lab has previously demonstrated that the incorporation of a glycoconjugate with the surface of a gold nanoparticle can enhance the immune response and increase protection in a murine model of inhalational glanders, a disease caused by the closely related host-adapted pathogen B. mallei (17).…”

mentioning

confidence: 99%

Use of Reverse Vaccinology in the Design and Construction of Nanoglycoconjugate Vaccines against Burkholderia pseudomallei

Muruato

Tapia

Hatcher

et al. 2017

Clin Vaccine Immunol

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Burkholderia pseudomallei is a Gram-negative, facultative intracellular pathogen that causes the disease melioidosis in humans and other mammals. Respiratory infection with B. pseudomallei leads to a fulminant and often fatal disease. It has previously been shown that glycoconjugate vaccines can provide significant protection against lethal challenge; however, the limited number of known Burkholderia antigens has slowed progress toward vaccine development. The objective of this study was to identify novel antigens and evaluate their protective capacity when incorporated into a nanoglycoconjugate vaccine platform. First, an in silico approach to identify antigens with strong predicted immunogenicity was developed. Protein candidates were screened and ranked according to predicted subcellular localization, transmembrane domains, adhesive properties, and ability to interact with major histocompatibility complex (MHC) class I and class II. From these in silico predictions, we identified seven "high priority" proteins that demonstrated seroreactivity with anti-B. pseudomallei murine sera and convalescent human melioidosis sera, providing validation of our methods. Two novel proteins, together with Hcp1, were linked to lipopolysaccharide (LPS) and incorporated with the surface of a gold nanoparticle (AuNP). Animals receiving AuNP glycoconjugate vaccines generated high proteinand polysaccharide-specific antibody titers. Importantly, immunized animals receiving the AuNP-FlgL-LPS alone or as a combination demonstrated up to 100% survival and reduced lung colonization following a lethal challenge with B. pseudomallei. Together, this study provides a rational approach to vaccine design that can be adapted for other complex pathogens and provides a rationale for further preclinical testing of AuNP glycoconjugate in animal models of infection.KEYWORDS Burkholderia pseudomallei, melioidosis, nanoglycoconjugate, nanovaccine, reverse vaccinology B urkholderia pseudomallei is a Gram-negative aerobic bacterium common to tropical and subtropical climates worldwide. This saprophytic bacterium can survive in soil and water and, upon transmission to humans or other susceptible mammals, cause the disease melioidosis. Human disease can present with a wide variety of clinical manifestations, including cutaneous and soft tissue abscesses, lymphadenopathy, and sepsis (1, 2). Clinical symptoms have been correlated with the route of infection; percutaneous infection often results in a purulent lesion at the site of inoculation, whereas respiratory

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Protection against Experimental Melioidosis following Immunisation with a Lipopolysaccharide-Protein Conjugate

Cited by 27 publications

References 43 publications

Melioidosis and glanders modulation of the innate immune system: barriers to current and future vaccine approaches

Melioidosis and glanders modulation of the innate immune system: barriers to current and future vaccine approaches

Immunisation with proteins expressed during chronic murine melioidosis provides enhanced protection against disease

Use of Reverse Vaccinology in the Design and Construction of Nanoglycoconjugate Vaccines against Burkholderia pseudomallei

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