Bacteria-enabled oral delivery of a replicon-based mRNA vaccine candidate protects against ancestral and delta variant SARS-CoV-2

Jawalagatti, Vijayakumar; Kirthika, Perumalraja; Hewawaduge, Chamith; Yang, Myeon‐Sik; Park, Jiyoung; Oh, Byung Kwan; Lee, John Hwa

doi:10.1016/j.ymthe.2022.01.042

Cited by 21 publications

(25 citation statements)

References 58 publications

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“…Moreover, gut bacteria can influence SIgA production in the lungs through CD103 + DCs ( 85 ). In agreement, we and others have documented the elicitation of mucosal response in respiratory sites by oral Salmonella -based vaccine administration ( 82 , 86 ). Further, Salmonella can translocate through M cells in the intestine and reach organs such as the liver and spleen, eliciting a systemic response as well ( 87 – 89 ).…”

Section: Advantages and Limitations Of Salmonella ...supporting

confidence: 91%

“…Our proof-of-principle studies using SARS-CoV-2 ( 25 , 81 , 82 ) provide evidence for the development of oral replicon-based mRNA vaccines against infectious diseases. Salmonella is an ideal bacterial vector owing to its unique ability to target GALT upon oral administration, resulting in both systemic and mucosal immune responses in vaccinated individuals.…”

Section: Oral Replicon-based Mrna Vaccine Against Sars-cov-2mentioning

confidence: 82%

“…Thus, asd serves as a powerful antibiotic-independent selection maker for bacterial delivery. This DNA-launched-mRNA vector design was exploited for the Salmonella- enabled oral delivery of a replicon-based mRNA vaccine against SARS-CoV-2 ( 25 , 81 , 82 ). The detailed mechanism of vector delivery, transgene amplification, and the generation of an immune response upon oral administration of Salmonella carrying the SFV replicon vector encoding vaccine immunogens is furnished in Figure 2 .…”

Section: Is It Possible To Orally Deliver Mrna Vaccines?mentioning

confidence: 99%

“…This figure was created with the help of the Biorender online tool ( ). The figure and description are reproduced with permission from Jawalagatti et al., 2022 (reference 82 ). ©The American Society of Gene and Cell Therapy.…”

Section: Is It Possible To Orally Deliver Mrna Vaccines?mentioning

confidence: 99%

“…To this end, we designed a multivalent SFV replicon-based vaccine targeting receptor-binding domain (RBD), heptad repeat domain (HR), membrane glycoprotein (M), and epitopes of nsp13 and employed Salmonella Typhimurium for gene delivery ( 25 ). The administration of the vaccine was highly safe in mice and hamsters inoculated both orally and intramuscularly ( 25 , 82 ). The vaccine elicited potent Th1-dominated humoral and cellular immune responses in mice against all the target antigens, suggesting efficient antigen production and presentation ( 25 , 82 ).…”

Section: Oral Replicon-based Mrna Vaccine Against Sars-cov-2mentioning

confidence: 99%

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Oral mRNA Vaccines Against Infectious Diseases- A Bacterial Perspective [Invited]

2022

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The mRNA vaccines from Pfizer/BioNTech and Moderna were granted emergency approval in record time in the history of vaccinology and played an instrumental role in limiting the pandemic caused by SARS-CoV-2. The success of these vaccines resulted from over 3 decades of research from many scientists. However, the development of orally administrable mRNA vaccine development is surprisingly underexplored. Our group specializing in Salmonella-based vaccines explored the possibility of oral mRNA vaccine development. Oral delivery was made possible by the exploitation of the Semliki Forest viral replicon and Salmonella vehicle for transgene amplification and gene delivery, respectively. Herein we highlight the prospect of developing oral replicon-based mRNA vaccines against infectious diseases based on our recent primary studies on SARS-CoV-2. Further, we discuss the potential advantages and limitations of bacterial gene delivery.

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Section: Advantages and Limitations Of Salmonella ...supporting

confidence: 91%

Section: Oral Replicon-based Mrna Vaccine Against Sars-cov-2mentioning

confidence: 82%

Section: Is It Possible To Orally Deliver Mrna Vaccines?mentioning

confidence: 99%

Section: Is It Possible To Orally Deliver Mrna Vaccines?mentioning

confidence: 99%

Section: Oral Replicon-based Mrna Vaccine Against Sars-cov-2mentioning

confidence: 99%

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Oral mRNA Vaccines Against Infectious Diseases- A Bacterial Perspective [Invited]

2022

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pH‐Responsive β‐Glucans‐Complexed mRNA in LNPs as an Oral Vaccine for Enhancing Cancer Immunotherapy

Luo,

Ho,

Chiang

et al. 2024

Advanced Materials

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AbstractmRNA vaccines for cancer immunotherapy are commonly delivered using lipid nanoparticles (LNPs), which, when administered intravenously, may accumulate in the liver, potentially limiting their therapeutic efficacy. To overcome this challenge, the study introduces an oral mRNA vaccine formulation tailored for efficient uptake by immune cells in the gastrointestinal (GI) tract, known for its high concentration of immune cells, including dendritic cells (DCs). This formulation comprises mRNA complexed with β‐glucans (βGlus), a potential adjuvant for vaccines, encapsulated within LNPs (βGlus/mRNA@LNPs). The βGlus/mRNA complexes within the small compartments of LNPs demonstrate a distinctive ability to partially dissociate and reassociate, responding to pH changes, effectively shielding mRNA from degradation in the harsh GI environment. Upon oral administration to tumor‐bearing mice, βGlus/mRNA@LNPs are effectively taken up by intestinal DCs and local nonimmune cells, bypassing potential liver accumulation. This initiates antigen‐specific immune responses through successful mRNA translation, followed by drainage into the mesenteric lymph nodes to stimulate T cells and trigger specific adaptive immune responses, ultimately enhancing antitumor effects. Importantly, the vaccine demonstrates safety, with no significant inflammatory reactions observed. In conclusion, the potential of oral βGlus/mRNA@LNPs delivery presents a promising avenue in cancer immunotherapy, offering needle‐free and user‐friendly administration for widespread adoption and self‐administration.

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Advancement of Engineered Bacteria for Orally Delivered Therapeutics

Guo

Wang

Yue

et al. 2023

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The use of bacteria and their biotic components as therapeutics has shown great potential in the treatment of diseases. Orally delivered bacteria improve patient compliance compared with injection‐administered bacteria and are considered the preferred mode. However, due to the harsh gastrointestinal environment, the viability and therapeutic efficacy of orally delivered bacteria are significantly reduced in vivo. In recent years, with the rapid development of synthetic biology and nanotechnology, bacteria and biotic components have been engineered to achieve directed genetic reprogramming for construction and precise spatiotemporal control in the gastrointestinal tract, which can improve viability and therapeutic efficiency. Herein, a state‐of‐the‐art review on the current progress of engineered bacterial systems for oral delivery is provided. The different types of bacterial and biotic components for oral administration are first summarized. The engineering strategies of these bacteria and biotic components and their treatment of diseases are next systematically summarized. Finally, the current challenges and prospects of these bacterial therapeutics are highlighted that will contribute to the development of next‐generation orally delivered bacteriotherapy.

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Bacteria-enabled oral delivery of a replicon-based mRNA vaccine candidate protects against ancestral and delta variant SARS-CoV-2

Cited by 21 publications

References 58 publications

Oral mRNA Vaccines Against Infectious Diseases- A Bacterial Perspective [Invited]

Oral mRNA Vaccines Against Infectious Diseases- A Bacterial Perspective [Invited]

pH‐Responsive β‐Glucans‐Complexed mRNA in LNPs as an Oral Vaccine for Enhancing Cancer Immunotherapy

Advancement of Engineered Bacteria for Orally Delivered Therapeutics

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