Vaccine Technologies and Platforms for Infectious Diseases: Current Progress, Challenges, and Opportunities

Vaccination is a key component of public health policy with demonstrated cost-effective benefits in protecting both human and animal populations. Vaccines can be manufactured under multiple forms including, inactivated (killed), toxoid, live attenuated, virus-like particles, synthetic peptide, polysaccharide, polysaccharide conjugate (glycoconjugate), viral vectored (vector-based), nucleic acids (DNA and mRNA) and bacterial vector/synthetic antigen presenting cells. Several processes are used in the manufacturing of vaccines and recent developments in medical/biomedical engineering, biology, immunology, and vaccinology have led to the emergence of innovative nucleic acid vaccines, a novel category added to conventional and subunit vaccines. In this review, we have summarized recent advances in vaccine technologies and platforms focusing on their mechanisms of action, advantages, and possible drawbacks.

Three distinct proteases are responsible for overall cell surface proteolysis in Streptococcus thermophilus .

The lactic acid bacterium Streptococcus thermophilus was believed to display only two distinct proteases at the cell surface, namely the cell-envelope protease PrtS and the house-keeping protease HtrA. Using peptidomics, we demonstrate here the existence of an additional active cell-surface protease, which shares significant homology with the SepM protease of Streptococcus mutans . Although all three proteases—PrtS, HtrA, and SepM—are involved in the turnover of surface proteins, they demonstrate distinct substrate specificities. In particular, SepM cleaves proteins involved in cell wall metabolism and cell elongation, and its inactivation has consequences for cell morphology. When all three proteases are inactivated, the residual cell-surface proteolysis of S. thermophilus is approximately 5% of that of the wild-type strain. Importance Streptococcus thermophilus is a lactic acid bacterium widely used as a starter in the dairy industry. Due to its "generally recognized as safe" status and its weak cell-surface proteolytic activity, it is also considered to be a potential bacterial vector for heterologous protein production. Our identification of a new cell surface protease made it possible to construct a mutant strain with a 95% reduction in surface proteolysis, which could be useful in numerous biotechnological applications.

Effectors from a Bacterial Vector-Borne Pathogen Exhibit Diverse Subcellular Localization, Expression Profiles and Manipulation of Plant Defense

ABSTRACTClimate change is predicted to increase the prevalence of vector borne disease due to expansion of insect populations. Candidatus Liberibacter solanacearum (Lso) is a phloem-limited pathogen associated with multiple economically important diseases in Solanaceous crops. Little is known about the strategies and pathogenicity factors Lso uses to colonize vector and host. We determined the Lso effector repertoire by predicting SEC secreted proteins across four different Lso haplotypes. Compared with C. Liberibacter asiaticus, the causal agent of citrus Huanglongbing, Lso possess a more variable effector repertoire, with greater similarity between haplotypes infecting the same host. The localization of Lso effectors in Nicotiana revealed diverse subcellular targets. The majority of tested effectors were unable to suppress plant immune responses, indicating they possess unique activities. Expression profiling in tomato and the psyllid Bactericera cockerelli indicated Lso differentially interacts with its vector and host and can switch effector expression in response to the environment. This study reveals Lso effectors possess complex expression patterns, target diverse host organelles and the majority are unable to suppress host immune responses, unlike effectors from foliar plant pathogenic bacteria. A mechanistic understanding of Lso effector function will reveal novel targets and provide insight into phloem biology.

The role of bacterial super antigens in the immune response: From biology to cancer treatment

Aims: Encouraging results have been indicated preclinically and in patients using the bacterial super antigen. This review article intends to summarize the role of the super antigens that have been recently used in the treatment of cancer. In addition, the vector systems including lentiviral vectors, adeno-associated vector systems and retroviral vectors that are increasingly being used in basic and applied research were discussed. Most importantly, the new CRISPR technique has also been discussed in this literature review. Discussion: More successful therapies can be achieved by manipulating bacterial vector systems through incorporating genes related to the super antigens and cytokines. The products of SAg and cytokine genes contributes to the strong stimulation of immune system against tumor cells. They bind to MHC II molecules as well as the V beta regions of TCR and lead to the production of IL2 and other cytokines, the activation of antigen-presenting cells and T lymphocytes. Additionally, super antigens can be used to eradicate tumor cells. Better results in cancer treatment can be achieved by transferring super antigen genes and subsequent strong immune stimulation along with other cancer immunotherapy agents. Conclusion: Super antigens induce the proliferation of T lymphocytes and antigen-presenting cells by binding to MHCII molecules and V beta regions in T cell receptors. Therefore, the presentation of tumor cell antigens is increased. Additionally, the production of important cytokines by T cells and APCs contributes to the stimulation of immune response against tumor cells. The manipulation of bacterial vector systems through incorporating genes related to SAgs and other immune response factors is a good strategy for immune system stimulating and eradicating of tumor cells along with other immunotherapy agents.

Protocol for evaluating the abilities of diverse nitroaromatic prodrug metabolites to exit a model Gram negative bacterial vector

© 2020 The Authors Bacterial-directed enzyme-prodrug therapy (BDEPT) uses tumour-tropic bacteria armed with a genetically-encoded prodrug-converting enzyme to sensitise tumours to a systemically-administered prodrug. A strong bystander effect (i.e., efficient bacteria-to-tumour transfer of activated prodrug metabolites) is critical to maximise tumour cell killing and avoid bacterial self-sterilisation. To investigate the bystander effect in bacteria we developed a sensitive screen that utilised two Escherichia coli strains grown in co-culture. The first of these was an activator strain that overexpressed the E. coli nitroreductase NfsA, and the second was a nitroreductase null recipient strain bearing an SOS-GFP DNA damage responsive gene construct. In this system, induction of GFP by genotoxic prodrug metabolites can only occur following their transfer from the activator to the recipient cells. This can be monitored both in fluorescence based microtitre plate assays and by flow-cytometry, enabling modelling of the abilities of diverse nitroaromatic prodrug metabolites to exit a Gram negative vector.

Protocol for evaluating the abilities of diverse nitroaromatic prodrug metabolites to exit a model Gram negative bacterial vector

© 2020 The Authors Bacterial-directed enzyme-prodrug therapy (BDEPT) uses tumour-tropic bacteria armed with a genetically-encoded prodrug-converting enzyme to sensitise tumours to a systemically-administered prodrug. A strong bystander effect (i.e., efficient bacteria-to-tumour transfer of activated prodrug metabolites) is critical to maximise tumour cell killing and avoid bacterial self-sterilisation. To investigate the bystander effect in bacteria we developed a sensitive screen that utilised two Escherichia coli strains grown in co-culture. The first of these was an activator strain that overexpressed the E. coli nitroreductase NfsA, and the second was a nitroreductase null recipient strain bearing an SOS-GFP DNA damage responsive gene construct. In this system, induction of GFP by genotoxic prodrug metabolites can only occur following their transfer from the activator to the recipient cells. This can be monitored both in fluorescence based microtitre plate assays and by flow-cytometry, enabling modelling of the abilities of diverse nitroaromatic prodrug metabolites to exit a Gram negative vector.