Burkholderia pseudomallei OMVs derived from infection mimicking conditions elicit similar protection to a live-attenuated vaccine

Baker, Sarah M.; Settles, Erik W.; Davitt, Christopher J. H.; Gellings, Patrick; Kikendall, Nicole; Hoffmann, Joseph P.; Wang, Yihui; Bitoun, Jacob P.; Lodrigue, Kasi Russell; Sahl, Jason W.; Keim, Paul; Roy, Chad J.; McLachlan, James B.; Morici, Lisa A.

doi:10.1038/s41541-021-00281-z

Cited by 27 publications

(26 citation statements)

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“…The addition of the OMVs can mimic a live bacterium to stimulate the immune response [ 14 ]. Indeed, B. pseudomallei OMVs have recently been shown to behave like and elicit similar protection to a live-attenuated vaccine [ 37 ]. Here, we hypothesized that the addition of B. pseudomallei OMVs to HKST would boost the immune response to Salmonella alone and confer protection against challenge.…”

Section: Discussionmentioning

confidence: 99%

“…Administration of OMVs to other mucosal surfaces would be beneficial in defining their adjuvant role and whether they are capable of inducing both humoral and cellular immunity at any site or if this phenomenon is gut specific. In this study, we used B. pseudomallei OMVs based on previous literature showing their safety and efficacy both as a vaccine and an adjuvant [ 13 , 14 , 37 ]. Overall, this study highlights the first time that B. pseudomallei OMVs have been employed to adjuvant an oral vaccine.…”

Section: Discussionmentioning

confidence: 99%

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An Outer Membrane Vesicle-Adjuvanted Oral Vaccine Protects Against Lethal, Oral Salmonella Infection

et al. 2021

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Non-typhoidal salmonellosis, caused by Salmonella enterica serovar Typhimurium is a common fecal-oral disease characterized by mild gastrointestinal distress resulting in diarrhea, chills, fever, abdominal cramps, head and body aches, nausea, and vomiting. Increasing incidences of antibiotic resistant invasive non-typhoidal Salmonella infections makes this a global threat requiring novel treatment strategies including next-generation vaccines. The goal of the current study was to formulate a novel vaccine platform against Salmonella infection that could be delivered orally. To accomplish this, we created a Salmonella-specific vaccine adjuvanted with Burkholderia pseudomallei outer membrane vesicles (OMVs). We show that adding OMVs to a heat-killed oral Salmonella vaccine (HKST + OMVs) protects against a lethal, oral challenge with Salmonella. Further, we show that opsonizing anti-Salmonella antibodies are induced in response to immunization and that CD4 T cells and B cells can be induced when OMVs are used as the oral adjuvant. This study represents a novel oral vaccine approach to combatting the increasing problem of invasive Salmonella infections.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

An Outer Membrane Vesicle-Adjuvanted Oral Vaccine Protects Against Lethal, Oral Salmonella Infection

et al. 2021

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“…Furthermore, we demonstrated that OMVs could be selectively-enriched with intracellular stage-specific proteins, leading to robust humoral and cellular immune responses that exceeded those induced by a live-attenuated strain [14]. Notably, OMVs possessed inherent adjuvanticity and conferred vaccine protection in mice and NHPs without a requirement for exogenous adjuvant.…”

Section: Introductionmentioning

confidence: 95%

Bacterial-Derived Outer Membrane Vesicles are Potent Adjuvants that Drive Humoral and Cellular Immune Responses

et al. 2021

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Discovery and development of novel adjuvants that can improve existing or next generation vaccine platforms have received considerable interest in recent years. In particular, adjuvants that can elicit both humoral and cellular immune responses would be particularly advantageous because the majority of licensed vaccines are formulated with aluminum hydroxide (alum) which predominantly promotes antibodies. We previously demonstrated that bacterial-derived outer membrane vesicles (OMV) possess inherent adjuvanticity and drive antigen-specific antibody and cellular immune responses to OMV components. Here, we investigated the ability of OMVs to stimulate innate and adaptive immunity and to function as a stand-alone adjuvant. We show that OMVs are more potent than heat-inactivated and live-attenuated bacteria in driving dendritic cell activation in vitro and in vivo. Mice immunized with OMVs admixed with heterologous peptides generated peptide-specific CD4 and CD8 T cells responses. Notably, OMV adjuvant induced much greater antibody and B cell responses to co-delivered ovalbumin compared to the responses elicited by the adjuvants alum and CpG DNA. Additionally, pre-existing antibodies raised against the OMVs did not impair OMV adjuvanticity upon repeat immunization. These results indicate that vaccines adjuvanted with OMVs elicit robust cellular and humoral immune responses, supporting further development of OMV adjuvant for use in next-generation vaccines.

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“…Preclinical and clinical studies conducted with GMMA-based vaccines have addressed humoral responses but poorly the cellular response ( Figure 1C ). Baker and co-authors demonstrated that OMV could induce robust cellular immune responses that exceeded those induced by a live-attenuated strain ( 65 ).…”

Section: Gaps On Understanding the Basis Of Gmma Immunogenicity And Potential Challengesmentioning

confidence: 99%

GMMA-Based Vaccines: The Known and The Unknown

et al. 2021

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Generalized Modules for Membrane Antigens (GMMA) are outer membrane vesicles derived from Gram-negative bacteria engineered to provide an over-vesiculating phenotype, which represent an attractive platform for the design of affordable vaccines. GMMA can be further genetically manipulated to modulate the risk of systemic reactogenicity and to act as delivery system for heterologous polysaccharide or protein antigens. GMMA are able to induce strong immunogenicity and protection in animal challenge models, and to be well-tolerated and immunogenic in clinical studies. The high immunogenicity could be ascribed to their particulate size, to their ability to present to the immune system multiple antigens in a natural conformation which mimics the bacterial environment, as well as to their intrinsic self-adjuvanticity. However, GMMA mechanism of action and the role in adjuvanticity are still unclear and need further investigation. In this review, we discuss progresses in the development of the GMMA vaccine platform, highlighting successful applications and identifying knowledge gaps and potential challenges.

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Burkholderia pseudomallei OMVs derived from infection mimicking conditions elicit similar protection to a live-attenuated vaccine

Cited by 27 publications

References 50 publications

An Outer Membrane Vesicle-Adjuvanted Oral Vaccine Protects Against Lethal, Oral Salmonella Infection

An Outer Membrane Vesicle-Adjuvanted Oral Vaccine Protects Against Lethal, Oral Salmonella Infection

Bacterial-Derived Outer Membrane Vesicles are Potent Adjuvants that Drive Humoral and Cellular Immune Responses

GMMA-Based Vaccines: The Known and The Unknown

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