Enhanced vaccine antigen delivery by Salmonella using antibiotic-free operator–repressor titration-based plasmid stabilisation compared to chromosomal integration

2009 ◽  
Vol 46 (4) ◽  
pp. 201-206 ◽  
Author(s):  
Matthew W. Leckenby ◽  
Abigail M. Spear ◽  
Brendan N. Neeson ◽  
E. Diane Williamson ◽  
Rocky M. Cranenburgh ◽  
...  
Author(s):  
Günther M. Keil ◽  
Reiko Pollin ◽  
Claudia Müller ◽  
Katrin Giesow ◽  
Horst Schirrmeier

2010 ◽  
Vol 78 (11) ◽  
pp. 4828-4838 ◽  
Author(s):  
Xin Xu ◽  
Mohamed I. Husseiny ◽  
Andreas Goldwich ◽  
Michael Hensel

ABSTRACT Salmonella enterica is a versatile vaccine carrier for heterologous antigens. One strategy for vaccine antigen delivery is the use of live attenuated S. enterica strains that translocate heterologous antigens into antigen-presenting cells by means of type III secretion systems (T3SS). The feasibility of this approach has been demonstrated in various experimental vaccination studies. The efficacy of recombinant live vaccines is critically influenced by the optimal level of attenuation and many other factors. For the rational design of approaches involving translocation by T3SS, additional parameters are the level of expression of the heterologous antigens and the selection of carrier proteins for the delivery of antigens to desirable subcellular compartments of the target cell. We deployed the Salmonella pathogenicity island 2 (SPI2)-encoded T3SS for antigen delivery. The SPI2-T3SS and effector proteins are encoded by members of the large SsrAB regulon, including promoters with highly variable strength of expression. We investigated the effect of various in vivo-activated promoters of the SsrAB regulon on the efficacy of recombinant Salmonella vaccines. We observed that the use of promoters with higher strength results in greater synthesis of recombinant antigens and greater stimulation of T-cell responses in cell culture assays for the stimulation of T cells by the model antigen ovalbumin. In contrast, in vaccination experiments, promoters with a low level of expression resulted in the induction of higher amounts of T cells reactive to the model antigen listeriolysin. These results demonstrate that high-level expression of heterologous antigens does not necessarily result in optimal stimulation of immune responses.


2017 ◽  
Vol 2 (3) ◽  
pp. 1-12
Author(s):  
Tadesse B

Adenoviruses have moved to the forefront of vaccinology and are showing substantial prom ise as vehicles for antigen delivery for a number of vaccines currently being developed. Most studies to date have focused on human serotype adenoviruses, particularly human adenovirus type 5. Human serotype adenovirus vaccine vectors are particularly usef ul for development of veterinary vaccines as neutralizing antibodies to the vector will not usually be present in the vaccinates. Most vectors currently used as vaccine carriers are deleted in E1 gene. The original E1 deleted adenoviral vectors were constr ucted by homologous recombination. Replication incompetent vectors contain an antigen expression cassette substituted for the deleted E1A – E1B region. These replication incompitant adenoviruses can not replicate because of the deletion of the essential vir al E1 gene region containing two genes. Replication competent adenoviral vectors encode all of the remaining adenoviral antigens in addition to the transgene product, i.e., the vaccine antigen. The potential for adenoviruses to elicit powerful B cell and T cell responses in the mammalian host are the main reason for the use of these vectors in vaccine development. For effective veterinary use, extensive research on adenoviral vaccine vectors should be undertaken.


Nano LIFE ◽  
2013 ◽  
Vol 03 (03) ◽  
pp. 1342002
Author(s):  
JOSEPH ROSENTHAL ◽  
TIFFANY LEUNG ◽  
MATTHEW DELISA ◽  
DAVID PUTNAM

The use of engineered antigen carriers to optimize the immune response to recombinant subunit vaccines has seen great advances in recent years. Optimization can take several forms, such as facilitating stimulation of certain immune cells or amplifying the adjuvancy effect of the vaccine formulation. In this paper, we applied dose/response analysis to demonstrate the ability of outer membrane vesicle (OMV) antigen carriers derived from engineered Escherichia coli to produce strong antigen-specific immune responses to a model antigen at a significantly decreased antigen load compared to an industry standard alum-based control. Inflammopathology and histological analysis of extended studies further supported a capacity to enhance immune cell recruitment locally at the injection site while decreasing inflammation and eliminating injection site scaring. The results indicate a strong potential for OMV-based vaccines as recombinant antigen delivery vehicles, affording strong immunogenicity at low doses with a broadly applicable platform for recombinant subunit antigen inclusion.


2020 ◽  
Vol 28 ◽  
Author(s):  
Alireza Milani ◽  
Kazem Baesi ◽  
Elnaz Agi ◽  
Ghazal Marouf ◽  
Maryam Ahmadi ◽  
...  

Background:: The combination antiretroviral therapy (cART) could increase the number of circulating naive CD4 T lymphocytes, but was not able to eradicate human immunodeficiency virus-1 (HIV-1) infection. Objective:: Thus, induction of strong immune responses is important for control of HIV-1 infection. Furthermore, a simple and perfect serological method is required to detect virus in untreated-, treated- and drug resistant- HIV-1 infected individuals. Methods:: This study was conducted to assess and compare immunogenic properties of Nef, Vif, Vpr and Vpu accessory proteins as an antigen candidate in mice and their diagnostic importance in human as a biomarker. Results:: Our data showed that in mice, all heterologous prime/ boost regimens were more potent than homologous prime/ boost regimens in eliciting Th1 response and Granzyme B secretion as CTL activity. Moreover, the Nef, Vpu and Vif proteins could significantly increase Th1 immune response. In contrast, the Vpr protein could considerably induce Th2 immune response. On the other hand, among four accessory proteins, HIV-1 Vpu could significantly detect treated group from untreated group as a possible biomarker in human. Conclusion:: Generally, among accessory proteins, Nef, Vpu and Vif antigens were potentially more suitable vaccine antigen candidates than Vpr antigen. Human antibodies against all these proteins were higher in HIV-1 different groups than healthy group. Among them, Vpu was known as a potent antigen in diagnosis of treated from untreated individuals. The potency of accessory proteins as an antigen candidate in an animal model and a human cohort study are underway.


Sign in / Sign up

Export Citation Format

Share Document