Oral Immunization with Recombinant<i>Listeria monocytogenes</i>Controls Virus Load after Vaginal Challenge with Feline Immunodeficiency Virus

Stevens, R. H.; Howard, Kristina E.; Nordone, Sushila K.; Burkhard, MaryJo; Dean, Gregg A.

doi:10.1128/jvi.78.15.8210-8218.2004

Cited by 38 publications

(44 citation statements)

References 78 publications

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“…Three months after oral immunisation with a recombinant L. monocytogenes that expresses the FIV Gag and delivers an FIV Env-expressing DNA, cats were vaginally challenged with a molecular clone of FIV. Whilst virus was isolated from four of the five immunised cats, further analysis indicated that viral load was reduced [48]. Taken together, these studies highlight the potential of the mucosal route of immunisation and support the widely held dogma that live vaccines are more effective than killed or subunit vaccines.…”

Section: Induction Of Mucosal Immune Responsessupporting

confidence: 52%

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Mucosal defence along the gastrointestinal tract of cats and dogs

Stokes

Waly

2006

Vet. Res.

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-Diseases that are associated with infections or allergic reactions in the gastrointestinal and respiratory tracts are major causes of morbidity in both cats and dogs. Future strategies for the control of these conditions require a greater understanding of the cellular and molecular mechanisms involved in the induction and regulation of responses at the mucosal surfaces. Historically, the majority of the fundamental studies have been carried out in rodents or with tissues obtained from man, but the expanding range of reagents available for the study of farm and companion animals provides opportunities for study in a wider range of animals including cats and dogs. To date, these studies have tended to be focussed on characterising the cellular distributions in healthy animals and in groups of cats and dogs identified as having an increased risk of mucosal disturbance. Where species comparisons of mucosal immune systems have been made, the results have tended to be divided between monogastric and ruminant animals. It is then not surprising that the mucosal immune systems of both cats and dogs bear greatest similarity to that documented for man and pigs.

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Section: Induction Of Mucosal Immune Responsessupporting

confidence: 52%

“…Fewer studies have investigated the numbers of IEL in the large intestine, but Dobbins [17] reported 5% epithelial cells in man and Atkins and Schofield [3] 2% epithelial cells in dogs. The numbers of IEL in the feline large intestine are similar (about 4% epithelial cells) [48].…”

Section: Inductive and Effector Sitesmentioning

confidence: 96%

Mucosal defence along the gastrointestinal tract of cats and dogs

Stokes

Waly

2006

Vet. Res.

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“…The attenuated strain of L. monocytogenes described here, L. monocytogenes dal dat/pRRR, which utilizes a host-induced recombination system to regulate D-alanine availability, appears to provide good immunogenicity while remaining highly attenuated. Therefore, it may be a promising vaccine against listeriosis or act as a vaccine carrier for use against other intracellular bacterial pathogens (31), viruses (19,22,28,48,54), tumors (6,38), and parasites (52).…”

Section: Discussionmentioning

confidence: 99%

“…Bypassing the gastrointestinal tract could lead to differences in dissemination. Moreover, oral immunization of L. monocytogenes as a vaccine is clearly the preferred route, not only because of the convenience of administration, but also because of the possibility of inducing mucosal immunity at the site of infection for many viral pathogens (19,22,48,54). Using an L. monocytogenes dal dat-based recombinant of L. monocytogenes expressing HIV type 1 gag, we previously showed that oral immunization of BALB/c mice generated protective mucosal anti-HIV gag CD8 ϩ T lymphocytes, thus supporting the possible development of an oral anti-HIV vaccine (18,(41)(42)(43).…”

Section: Discussionmentioning

confidence: 99%

Pathogenicity and Immunogenicity of a Vaccine Strain ofListeria monocytogenesThat Relies on a Suicide Plasmid To Supply an Essential Gene Product

Zhao

et al. 2005

Infect Immun

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Listeria monocytogenes is a bacterial pathogen that elicits a strong cellular immune response and thus has potential use as a vaccine vector. An attenuated strain, L. monocytogenes dal dat, produced by deletion of two genes (dal and dat) used for D-alanine synthesis, induces cytotoxic T lymphocytes and protective immunity in mice following infection in the presence of D-alanine. In order to obviate the dependence of L. monocytogenes dal dat on supplemental D-alanine yet retain its attenuation and immunogenicity, we explored mechanisms to allow transient endogenous synthesis of the amino acid. Here, we report on a derivative strain, L. monocytogenes dal dat/pRRR, that expresses a dal gene and synthesizes D-alanine under highly selective conditions. We constructed the suicide plasmid pRRR carrying a dal gene surrounded by two res1 sites and a resolvase gene, tnpR, which acts at the res1 sites. The resolvase gene is regulated by a promoter activated upon exposure to host cell cytosol. L. monocytogenes dal dat/pRRR was thus able to grow in liquid culture and to infect host cells without D-alanine supplementation. However, after infection of these cells, resolvase-mediated excision of the dal gene resulted in strong down-regulation of racemase expression. As a result, this system allowed only transient growth of L. monocytogenes dal dat/pRRR in infected cells and survival in animals for only 2 to 3 days. Nevertheless, mice immunized with L. monocytogenes dal dat/pRRR generated listeriolysin O-specific effector and memory CD8؉ T cells and were protected against lethal challenge by wild-type Listeria. This vector may be an attractive vaccine candidate for the induction of protective cellular immune responses.Listeria monocytogenes is a gram-positive, facultative intracellular, food-borne bacterium that elicits strong cell-mediated immunity (16,23). It has shown promise as a live vaccine vector against model cancers (6,20,34,36,38), Mycobacterium tuberculosis (31), influenza virus (22), and lymphocytic choriomeningitis virus (19,48) and has been suggested for use as an AIDS vaccine vector (17, 28). However, L. monocytogenes is itself a pathogen that can cause fatal infections, particularly in immune-compromised or pregnant individuals (14,21,59). Therefore, the safety of L. monocytogenes as a vaccine vector is a critical issue that could block the potential utility of this organism.An ideal vaccine strain of any living organism must be highly attenuated but fully immunogenic. To achieve this, various mutations in virulence-associated determinants of L. monocytogenes have been exploited for potential use as vaccine vectors (1,2,6,8,19,24,29,30,55,57), but many tend to have the limitation of either weak immunogenicity or insufficient avirulence. We developed a highly attenuated strain, L. monocytogenes dal dat, by inactivating two genes (dal and dat) essential for D-alanine biosynthesis (58). This strain requires the unusual amino acid D-alanine, not synthesized by vertebrates, for viability and infection. It showed no re...

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“…Head-to-head comparisons of intranasal and parenteral routes for delivery of recombinant Listeria vectors have not been reported. The recombinant Listeria vaccine vectors for infections reported to date by other investigators have been based on either wild-type Listeria (2,29) or Listeria deleted of the essential D-alanine synthesis pathway (9), thus raising safety concerns (with the wild type) or requiring special D-alanine supplemental treatments during vaccination of animals (dal dat mutants). We recently demonstrated that attenuated the Listeria ⌬actA prfA*strain is a promising vaccine vector, since r-Listeria ⌬actA prfA* secretes Ͼ100-fold-higher levels of vaccine immunogens in broth culture than wild-type r-Listeria or r-Listeria ⌬actA, and it elicits much higher magnitudes of immunogen-specific humoral and cellular immune responses after intravenous vaccination of mice than those induced by r-Listeria ⌬actA (32).…”

Section: Discussionmentioning

confidence: 99%

Intranasal Vaccination with the Recombinant Listeria monocytogenes ΔactA prfA*Mutant Elicits Robust Systemic and Pulmonary Cellular Responses and Secretory Mucosal IgA

Qiu

Lin

Chen

et al. 2011

Clin. Vaccine Immunol.

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We previously showed that recombinant (r) Listeria monocytogenes carrying ⌬actA and a selected prfA* mutation (r-Listeria ⌬actA prfA*) secreted >100-fold more immunogen in broth culture than wild-type r-Listeria or r-Listeria ⌬actA and elicited much greater cellular and humoral immune responses than r-Listeria ⌬actA after intravenous vaccination of mice. Here, we conducted comparative studies evaluating vaccine-elicited immune responses in systemic and mucosal sites after intranasal, intravenous, intraperitoneal, or subcutaneous immunization of mice with r-Listeria ⌬actA prfA* vaccine candidates. Intranasal vaccination of mice with r-Listeria ⌬actA prfA* vaccine candidates elicited a robust gamma interferon-positive (IFN-␥ ؉ ) cellular response in systemic sites, although intravenous or intraperitoneal immunization was more efficient. Surprisingly, intranasal vaccination elicited an appreciable pulmonary IFN-␥ ؉ cellular response that was nonstatistically higher than the magnitude induced by the intravenous route but was significantly greater than that elicited by subcutaneous immunization. Furthermore, although intranasal r-Listeria ⌬actA prfA* delivery induced poor systemic IgG responses, intranasal vaccination elicited appreciable secretory immunogen-specific IgA titers that were similar to or higher in mucosal fluid than those induced by subcutaneous and intravenous immunizations. Thus, intranasal vaccination with r-Listeria ⌬actA prfA* appears to be a useful approach for eliciting robust systemic and pulmonary cellular responses and measurable secretory mucosal IgA titers.Listeria monocytogenes is an intracellular bacterium with the unique ability to live in the cytoplasm and escape to the cytosol of antigen-presenting cells (APC). Listeria therefore can serve as a useful bacterial vaccine vector to deliver immunogens and to elicit strong CD8 ϩ T-cell immune responses (5,7,23,26,31). Since the deletion of the actA gene in L. monocytogenes results in remarkable attenuation without affecting immune potency, Listeria lacking actA have been explored as vaccine candidates for delivering immunogens against cancers (3,4,24). We recently showed that recombinant (r) Listeria ⌬actA vectors carrying a selected prfA(G155S) mutation (Listeria ⌬actA prfA*) secreted Ͼ100-fold-higher levels of vaccine immunogens in broth culture than wild-type r-Listeria or r-Listeria ⌬actA and consistently elicited much greater cellular and humoral immune responses than r-Listeria ⌬actA vectors after intravenous (i.v.) vaccination of mice (32).

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Oral Immunization with RecombinantListeria monocytogenesControls Virus Load after Vaginal Challenge with Feline Immunodeficiency Virus

Abstract: Recombinant Listeria monocytogenes has many attractive characteristics as a vaccine vector against human immunodeficiency virus (HIV). Wild-type and attenuated

Cited by 38 publications

References 78 publications

Mucosal defence along the gastrointestinal tract of cats and dogs

Mucosal defence along the gastrointestinal tract of cats and dogs

Pathogenicity and Immunogenicity of a Vaccine Strain ofListeria monocytogenesThat Relies on a Suicide Plasmid To Supply an Essential Gene Product

Intranasal Vaccination with the Recombinant Listeria monocytogenes ΔactA prfA*Mutant Elicits Robust Systemic and Pulmonary Cellular Responses and Secretory Mucosal IgA

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