Design and immune characterization of a novel Neisseria gonorrhoeae DNA vaccine using bacterial ghosts as vector and adjuvant

Aim Gonorrhoea remains a leading public health burden and the development of vaccine against gonorrhoea becomes more urgent. Here, a novel Neisseria gonorrhoeae DNA vaccine delivered by Salmonella enteritidis ghosts was developed and the immune responses of the vaccine candidate were evaluated. Methods and Results Neisseria gonorrhoeae nspA gene was cloned into the pVAX1 vector. The constructed recombinant plasmid pVAX1‐nspA was loaded into the lyophilized SE ghosts to produce SE ghosts (pVAX1‐nspA). Then, the immune responses induced by SE ghosts (pVAX1‐nspA) alone and co‐administrated with SE ghosts (pVAX1‐porB) were evaluated in mouse model. Co‐administered SE ghosts (pVAX1‐nspA) and SE ghosts (pVAX1‐porB) could elicited significantly higher levels of specific IgG antibody responses and lymphocyte proliferative responses than the control groups. Furthermore, the group co‐administered SE ghosts (pVAX1‐nspA) and SE ghosts (pVAX1‐porB) had the highest bactericidal antibody titres. Conclusions Co‐administration of SE ghosts (pVAX1‐nspA) and SE ghosts (pVAX1‐porB) elicited significant specific humoral and cellular immune responses. Significance and Impact of the Study This study demonstrates the potential of co‐administration of SE ghosts (pVAX1‐nspA) and SE ghosts (pVAX1‐porB) as an attractive vaccination regimen for gonorrhoea.

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“…Neisseria gonorrhoeae porB gene vaccine‐loaded S. enteritidis ghosts were produced as previously described (Jiao et al . 2018).…”

Section: Methodsmentioning

confidence: 99%

“…2011; Jiao et al . 2018). In addition, previous studies have demonstrated that immunogenicity of single antigen vaccine is low and a proper adjuvant or delivery system need to be used to induce protective immune responses.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of immune responses by co‐administration of bacterial ghosts‐mediated Neisseria gonorrhoeae DNA vaccines

et al. 2020

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“…In the intestine, these bacteria may be phagocytosed directly by mucosal DC/macrophages spreading extensions into the gut lumen or after M cell-mediated transcytosis at the Peyer’s patches [ 225 ]. After phagocytosis, plasmid DNA is released from phagolysosome, and the numerous bacteria-associated danger signals result in profound APC activation [ 226 ]. More recently, ‘bacterial ghosts’ which constitute only the bacterial envelope have been introduced as carriers for DNA vaccines [ 227 ].…”

Section: Route Of Vaccinationmentioning

confidence: 99%

DNA Vaccines—How Far From Clinical Use?

Hobernik

Bros

2018

IJMS

371

332

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Two decades ago successful transfection of antigen presenting cells (APC) in vivo was demonstrated which resulted in the induction of primary adaptive immune responses. Due to the good biocompatibility of plasmid DNA, their cost-efficient production and long shelf life, many researchers aimed to develop DNA vaccine-based immunotherapeutic strategies for treatment of infections and cancer, but also autoimmune diseases and allergies. This review aims to summarize our current knowledge on the course of action of DNA vaccines, and which factors are responsible for the poor immunogenicity in human so far. Important optimization steps that improve DNA transfection efficiency comprise the introduction of DNA-complexing nano-carriers aimed to prevent extracellular DNA degradation, enabling APC targeting, and enhanced endo/lysosomal escape of DNA. Attachment of virus-derived nuclear localization sequences facilitates nuclear entry of DNA. Improvements in DNA vaccine design include the use of APC-specific promotors for transcriptional targeting, the arrangement of multiple antigen sequences, the co-delivery of molecular adjuvants to prevent tolerance induction, and strategies to circumvent potential inhibitory effects of the vector backbone. Successful clinical use of DNA vaccines may require combined employment of all of these parameters, and combination treatment with additional drugs.

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“…Another new delivery approach that has been studied utilizes bacterial ghosts [ 168 , 169 , 170 ], where a native bacterial outer membrane (with or without LPS [ 170 ]) is utilized to encapsulate the desired antigen. This was reported to be effective in inducing dendritic cell maturation in comparison to LPS-based protocols [ 168 ], but may carry the risk of a too-low specific antibody titer.…”

Section: Alternative Immunization Approaches From Other Research Fmentioning

confidence: 99%

Innovative Immunization Strategies for Antivenom Development

Bermúdez-Méndez

Fuglsang-Madsen

Føns

et al. 2018

Toxins

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Snakes, scorpions, and spiders are venomous animals that pose a threat to human health, and severe envenomings from the bites or stings of these animals must be treated with antivenom. Current antivenoms are based on plasma-derived immunoglobulins or immunoglobulin fragments from hyper-immunized animals. Although these medicines have been life-saving for more than 120 years, opportunities to improve envenoming therapy exist. In the later decades, new biotechnological tools have been applied with the aim of improving the efficacy, safety, and affordability of antivenoms. Within the avenues explored, novel immunization strategies using synthetic peptide epitopes, recombinant toxins (or toxoids), or DNA strings as immunogens have demonstrated potential for generating antivenoms with high therapeutic antibody titers and broad neutralizing capacity. Furthermore, these approaches circumvent the need for venom in the production process of antivenoms, thereby limiting some of the complications associated with animal captivity and venom collection. Finally, an important benefit of innovative immunization approaches is that they are often compatible with existing antivenom manufacturing setups. In this review, we compile all reported studies examining venom-independent innovative immunization strategies for antivenom development. In addition, a brief description of toxin families of medical relevance found in snake, scorpion, and spider venoms is presented, as well as how biochemical, bioinformatic, and omics tools could aid the development of next-generation antivenoms.

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Design and immune characterization of a novel Neisseria gonorrhoeae DNA vaccine using bacterial ghosts as vector and adjuvant

Cited by 29 publications

References 31 publications

Enhancement of immune responses by co‐administration of bacterial ghosts‐mediated Neisseria gonorrhoeae DNA vaccines

Enhancement of immune responses by co‐administration of bacterial ghosts‐mediated Neisseria gonorrhoeae DNA vaccines

DNA Vaccines—How Far From Clinical Use?

Innovative Immunization Strategies for Antivenom Development

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