Systemic Immunity and Mucosal Immunity Are Induced against Human Immunodeficiency Virus Gag Protein in Mice by a New Hyperattenuated Strain of<i>Listeria monocytogenes</i>

Rayevskaya, Marina; Frankel, Fred R.

doi:10.1128/jvi.75.6.2786-2791.2001

Cited by 50 publications

(56 citation statements)

References 46 publications

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“…Lm poses potential risks for pregnant women, neonates and immunocompromised individuals [44]. The attenuated Lm vector used here, Lmdd-gag, was shown previously to be safe and immunogenic in adult and neonatal mice [34,35]. Here, we demonstrated that Lmdd-gag, as well as accompanying D-ala, were safe in monkeys when administered at levels that were able to induce Gag-specific immune responses.…”

Section: Discussionmentioning

confidence: 57%

“…As our pilot study was undertaken primarily to assess the safety of live attenuated Lmdd-gag in monkeys, we did not directly sample mucosal sites for cellular immunity and were limited to assessing PBMC, which clearly showed Gag-directed cellular immune responses. Future studies will investigate mucosal immune responses to determine whether the same high levels of antigen-specific cellular immune responses can be generated at mucosal sites in primates as have been demonstrated in mice [34].…”

Section: Discussionmentioning

confidence: 94%

“…The resulting bacteria, Lmdd-gag, generated HIV Gag-specific CD8 + CTL responses, both systemically and within Peyer's patches and mesenteric lymph nodes, in vaccinated mice [34]. Furthermore, Lmddgag-immunized mice were protected from challenge with recombinant vaccinia virus expressing HIV gag [34].…”

Section: Introductionmentioning

confidence: 99%

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Live attenuated Listeria monocytogenes expressing HIV Gag: Immunogenicity in rhesus monkeys

Jiang

Rasmussen

Nolan

et al. 2007

Vaccine

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Induction of strong cellular immunity will be important for AIDS vaccine candidates. Natural infection with wild-type Listeria monocytogenes (Lm), an orally transmitted organism, is known to generate strong cellular immunity, thus raising the possibility that live attenuated Lm could serve as a vaccine vector. We sought to examine the potential of live attenuated Lm to induce cellular immune responses to HIV Gag. Rhesus macaques were immunized with Lmdd-gag that expresses HIV gag and lacks two genes in the D-alanine (D-ala) synthesis pathway. Without this key component of the bacterial cell wall, vaccine vector replication critically depends on exogenous D-ala. Lmdd-gag was given to animals either solely orally or by oral priming followed by intramuscular (i.m.) boosting; D-ala was co-administered with all vaccinations. Lmdd-gag and D-ala were well tolerated. Oral priming/oral boosting induced Gag-specific cellular immune responses, whereas oral priming/i.m. boosting induced systemic as well as mucosal anti-Gag antibodies. These results suggest that the route of vaccination may bias anti-Gag immune responses either towards T-helper type 1 (Th1) or Th2 responses; overall, our data show that live attenuated, recombinant Lmdd-gag was safe and immunogenic in primates.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 94%

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Live attenuated Listeria monocytogenes expressing HIV Gag: Immunogenicity in rhesus monkeys

Jiang

Rasmussen

Nolan

et al. 2007

Vaccine

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“…Preclinical as well as clinical trials with these constructs yielded disappointing results as the neutralizing Abs induced by such vaccines lacked the breath to provide solid protection against different HIV-1 isolates (21,22). Subsequent vaccine efforts were directed at inducing cell-mediated immune responses (6,(23)(24)(25). Optimized DNA vaccines expressing the gag of HIV-1 provided initial protection to nonhuman primates challenged with SHIV-89.6P virus (26).…”

Section: Discussionmentioning

confidence: 99%

Induction of CD8+ T Cells to an HIV-1 Antigen through a Prime Boost Regimen with Heterologous E1-Deleted Adenoviral Vaccine Carriers

Pinto

Fitzgerald

Giles-Davis

et al. 2003

The Journal of Immunology

106

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E1-deleted adenoviral recombinants most commonly based on the human serotype 5 (AdHu5) have been shown thus far to induce unsurpassed transgene product-specific CD8+ T cell responses. A large percentage of the adult human population carries neutralizing Abs due to natural exposures to AdHu5 virus. To circumvent reduction of the efficacy of adenovirus (Ad) vector-based vaccines by neutralizing Abs to the vaccine carrier, we developed E1-deleted adenoviral vaccine carriers based on simian serotypes. One of these carriers, termed AdC68, expressing a codon-optimized truncated form of gag of HIV-1 was shown previously to induce a potent transgene product-specific CD8+ T cell response in mice. We constructed a second chimpanzee adenovirus vaccine vector, termed AdC6, also expressing the truncated gag of HIV-1. This vector, which belongs to a different serotype than the AdC68 virus, induces high frequencies of gag-specific CD8+ T cells in mice including those pre-exposed to AdHu5 virus. Generation of an additional E1-deleted adenoviral vector of chimpanzee origin allows for sequential booster immunizations with heterologous vaccine carriers. In this study, we show that such heterologous prime boost regimens based on E1-deleted adenoviral vectors of different serotypes expressing the same transgene product are highly efficient in increasing the transgene product-specific CD8+ T cell response. They are equivalent to sequential vaccinations with an E1-deleted Ad vector followed by booster immunization with a poxvirus vector and they surpass regimens based on DNA vaccine prime followed by a recombinant adenoviral vector boost.

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“…Mainly using 51 Cr release CTL assays or protection with and without T cell depletion, our group and other researchers have shown that Gag expressing recombinant Listeria can induce Gag-specific CTL (36,41,53). Indeed, Rayevskaya and Frankel (36) employed a highly attenuated Listeria mutant, incapable of incorporating Dalanine into the cell wall, to deliver HIV Gag by the oral route with the induction of CTL activity in the spleen, MLN, and PP.…”

Section: Discussionmentioning

confidence: 99%

The Induction of HIV Gag-Specific CD8+ T Cells in the Spleen and Gut-Associated Lymphoid Tissue by Parenteral or Mucosal Immunization with RecombinantListeria monocytogenesHIV Gag

Peters

Peng

Douven

et al. 2003

The Journal of Immunology

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The induction of mucosal immunity is crucial in controlling viral replication during HIV infection. In this study we compare the ability of a recombinant Listeria monocytogenes that expresses and secretes the HIV Ag Gag to induce CD8+ T cells against this Ag in the spleen, mesenteric lymph nodes, and Peyer’s patches and the ability to provide effector Gag-specific CD8+ T cells to the lamina propria after i.v., oral, or rectal administration of the vaccine. The levels of Ag-specific CD8+-activated T cells were measured ex vivo using intracellular cytokine staining for IFN-γ and H-2Kd Gag peptide tetramer staining. We found that all routes of immunization induced Gag-specific CD8+ T cells in the spleen. After secondary infection, we observed substantial increases in splenic levels of CD8+ T cells, and levels of Gag-specific cells were similar to those against listeriolysin O, the immunodominant Ag of L. monocytogenes. Both primary and secondary oral immunization resulted in abundant Gag-specific CD8+-activated T cells in the lamina propria that constituted ∼35% of the CD8 compartment. However, significant levels of Gag and listeriolysin O-specific CD8+ T cells were observed in mucosal lymphoid tissue only after two immunizations, perhaps because they had already entered the lamina propria compartment after a single immunization. In the context of HIV, a mucosally administered vaccine seems best calculated to prompt an immune response that is capable of preventing infection. The data presented in this report demonstrate that mucosally administered Listeria can prompt such a response and that booster doses can maintain this response.

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Systemic Immunity and Mucosal Immunity Are Induced against Human Immunodeficiency Virus Gag Protein in Mice by a New Hyperattenuated Strain ofListeria monocytogenes

Cited by 50 publications

References 46 publications

Live attenuated Listeria monocytogenes expressing HIV Gag: Immunogenicity in rhesus monkeys

Live attenuated Listeria monocytogenes expressing HIV Gag: Immunogenicity in rhesus monkeys

Induction of CD8+ T Cells to an HIV-1 Antigen through a Prime Boost Regimen with Heterologous E1-Deleted Adenoviral Vaccine Carriers

The Induction of HIV Gag-Specific CD8+ T Cells in the Spleen and Gut-Associated Lymphoid Tissue by Parenteral or Mucosal Immunization with RecombinantListeria monocytogenesHIV Gag

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