Mucosal immunization of BALB/c mice with DNA vaccines encoding the SEN1002 and SEN1395 open reading frames of Salmonella enterica serovar Enteritidis induces protective immunity

2015 ◽  
Vol 144 (2) ◽  
pp. 247-256 ◽  
Author(s):  
J. BELLO ◽  
D. SÁEZ ◽  
E. ESCALONA ◽  
P. VELOZO ◽  
C. A. SANTIVIAGO ◽  
...  

SUMMARYSalmonella Enteritidis is the main cause of foodborne salmonellosis worldwide. The limited effectiveness of current interventions against this pathogen has been the main incentive to develop new methods for the efficient control of this infection. To investigate the use of DNA vaccines against S. Enteritidis in humans, immune responses stimulated by two plasmids containing the genes designated SEN1002, located in the pathogenicity island SPI-19 and encoding a Hcp protein involved in transport mechanisms, and SEN1395, located in the genomic island ΦSE14 and encoding a protein of a new superfamily of lysozymes, were evaluated. Humoral and cellular responses following intranasal immunization of two groups of BALB/c mice with the plasmids pV1002 and pV1395 plus adjuvant were evaluated and it was observed that the IgG2a/IgG1 ratios were sixfold higher than control groups. Both plasmids stimulated specific secretory IgA production. Increased proliferation of lymphocytes and IFN-γ production were detected in both experimental groups. DNA-vaccinated mice developed protective immunity against a virulent strain of S. Enteritidis, with nearly 2 logs of protection level compared to the negative control values in the spleen. Therefore, DNA vaccines are efficient at stimulating cellular and humoral immune responses at systemic and mucosal levels.

2013 ◽  
Vol 81 (12) ◽  
pp. 4626-4634 ◽  
Author(s):  
Ediane B. Silva ◽  
Andrew Goodyear ◽  
Marjorie D. Sutherland ◽  
Nicole L. Podnecky ◽  
Mercedes Gonzalez-Juarrero ◽  
...  

ABSTRACTInfections with the Gram-negative bacteriumBurkholderia pseudomallei(melioidosis) are associated with high mortality, and there is currently no approved vaccine to prevent the development of melioidosis in humans. Infected patients also do not develop protective immunity to reinfection, and some individuals will develop chronic, subclinical infections withB. pseudomallei. At present, our understanding of what constitutes effective protective immunity againstB. pseudomalleiinfection remains incomplete. Therefore, we conducted a study to elucidate immune correlates of vaccine-induced protective immunity against acuteB. pseudomalleiinfection. BALB/c and C57BL/6 mice were immunized subcutaneously with a highly attenuated, Select Agent-excludedpurMdeletion mutant ofB. pseudomallei(strain Bp82) and then subjected to intranasal challenge with virulentB. pseudomalleistrain 1026b. Immunization with Bp82 generated significant protection from challenge withB. pseudomallei, and protection was associated with a significant reduction in bacterial burden in lungs, liver, and spleen of immunized mice. Humoral immunity was critically important for vaccine-induced protection, as mice lacking B cells were not protected by immunization and serum from Bp82-vaccinated mice could transfer partial protection to nonvaccinated animals. In contrast, vaccine-induced protective immunity was found to be independent of both CD4 and CD8 T cells. Tracking studies demonstrated uptake of the Bp82 vaccine strain predominately by neutrophils in vaccine-draining lymph nodes and by smaller numbers of dendritic cells (DC) and monocytes. We concluded that protection following cutaneous immunization with a live attenuatedBurkholderiavaccine strain was dependent primarily on generation of effective humoral immune responses.


2008 ◽  
Vol 76 (5) ◽  
pp. 2025-2036 ◽  
Author(s):  
Lauriane E. Quenee ◽  
Claire A. Cornelius ◽  
Nancy A. Ciletti ◽  
Derek Elli ◽  
Olaf Schneewind

ABSTRACT Yersinia pestis, the highly virulent agent of plague, is a biological weapon. Strategies that prevent plague have been sought for centuries, and immunization with live, attenuated (nonpigmented) strains or subunit vaccines with F1 (Caf1) antigen is considered effective. We show here that immunization with live, attenuated strains generates plague-protective immunity and humoral immune responses against F1 pilus antigen and LcrV. Y. pestis variants lacking caf1 (F1 pili) are not only fully virulent in animal models of bubonic and pneumonic plague but also break through immune responses generated with live, attenuated strains or F1 subunit vaccines. In contrast, immunization with purified LcrV, a protein at the tip of type III needles, generates protective immunity against the wild-type and the fully virulent caf1 mutant strain, in agreement with the notion that LcrV can elicit vaccine protection against both types of virulent plague strains.


2009 ◽  
Vol 77 (5) ◽  
pp. 1807-1816 ◽  
Author(s):  
Claire A. Cornelius ◽  
Lauriane E. Quenee ◽  
Derek Elli ◽  
Nancy A. Ciletti ◽  
Olaf Schneewind

ABSTRACTYersinia pestisis perhaps the most feared infectious agent due to its ability to cause epidemic outbreaks of plague disease in animals and humans with high mortality. Plague infections elicit strong humoral immune responses against the capsular antigen (fraction 1 [F1]) ofY. pestis, and F1-specific antibodies provide protective immunity. Here we asked whetherY. pestisgenerates mutations that enable bacterial escape from protective immunity and isolated a variant with an IS1541insertion incaf1Aencoding the F1 outer membrane usher. Thecaf1A::IS1541insertion prevented assembly of F1 pili and provided escape from plague immunity via F1-specific antibodies without a reduction in virulence in mouse models of bubonic or pneumonic plague. F1-specific antibodies interfere withY. pestistype III transport of effector proteins into host cells, an inhibitory effect that was overcome by thecaf1A::IS1541insertion. These findings suggest a model in which IS1541insertion intocaf1Aprovides for reversible changes in envelope structure, enablingY. pestisto escape from adaptive immune responses and plague immunity.


1998 ◽  
Vol 9 (2) ◽  
pp. 99-109 ◽  
Author(s):  
X Yang ◽  
RC Brunham

Chlamydia trachomatisis an obligate intracellular bacterial pathogen that causes several significant human infectious diseases, including trachoma, urethritis, cervicitis and salpingitis, and is an important cofactor for transmission of human immunodeficiency virus. Until very recently, over three decades of research effort aimed at developing aC trachomatisvaccine had failed, due mainly to the lack of a precise understanding of the mechanisms for protective immunity. Although most studies concerning protective immunity toC trachomatishave focused on humoral immune responses, recent studies have clearly shown that T helper-1 (Th1)-like CD4 T cell-mediated immune responses play the dominant role in protective immunity. These studies suggest a paradigm for chlamydial immunity and pathology based on the concept of heterogeneity (Th1/Th2) in CD4 T cell immune responses. This concept for chlamydial immunity offers a rational template on which to base renewed efforts for development of a chlamydial vaccine that targets the induction of cell-mediated Th1 immune responses.


2021 ◽  
Author(s):  
Jeffrey B Ulmer

DNA vaccines were first discovered more than 30 years ago. Because DNA vaccines result in antigen production in situ (i.e., mimic a virus infection), they elicit broad-based immune responses, including antibodies and T cells. Induction of protective immunity has been established in scores of animal models of infectious and non-infectious diseases. Hundreds of human clinical trials have been conducted demonstrating safety and, in many cases, antigen-specific immune responses. Several animal health vaccines based on DNA have been approved and are in use. Many DNA vaccines are in various stages of human clinical testing, including a few in phase 3 efficacy trials and the recent Emergency Use Authorization of a COVID-19 vaccine, but to date no DNA vaccines have been fully licensed for human use. DNA vaccines are thermostable and amenable to large-scale manufacturing at relatively low cost, hence well-suited for global use, particularly in the developing world. If potency in humans could be achieved, DNA vaccines would have the potential to be a radical innovation that could disrupt the vaccine industry.


2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Yi-jing Li ◽  
Guang-peng Ma ◽  
Gui-wei Li ◽  
Xin-yuan Qiao ◽  
Jun-wei Ge ◽  
...  

The objective of this study to design a delivery system resistant to the gastrointestinal environment for oral vaccine against porcine rotavirus.Lactococcus lactisNZ9000 was transformed with segments ofvP4of the porcine rotavirus inserted into the pNZ8112 surface-expression vector, and a recombinantL. lactisexpressing VP4 protein was constructed. An approximately 27 kDa VP4 protein was confirmed by SDS-PAGE , Western blot and immunostaining analysis. BALB/c mice were immunized orally with VP4-expression recombinantL. lactisand cellular, mucosal and systemic humoral immune responses were examined. Specific anti-VP4 secretory IgA and IgG were found in feces, ophthalmic and vaginal washes and in serum. The induced antibodies demonstrated neutralizing effects on porcine rotavirus infection on MA104 cells. Our findings suggest that oral immunization with VP4-expressingL. lactisinduced both specific local and systemic humoral and cellular immune responses in mice.


2019 ◽  
Vol 10 ◽  
Author(s):  
Martha Wium ◽  
Hester Isabella Jonker ◽  
Adriaan Jacobus Olivier ◽  
Dirk Uwe Bellstedt ◽  
Annelise Botes

Vaccine ◽  
2000 ◽  
Vol 18 (23) ◽  
pp. 2522-2532 ◽  
Author(s):  
Damien R. Drew ◽  
Marshall Lightowlers ◽  
Richard A. Strugnell

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