DNA prime Listeria boost induces a cellular immune response to SIV antigens in the rhesus macaque model that is capable of limited suppression of SIV239 viral replication

Abstract

DNA vaccines and recombinant Listeria monocytogenes that express and secrete SIV Gag and Env antigens were combined in a nonhuman primate prime-boost immunogenicity study followed by a challenge with SIV239. We report that recombinant DNA vaccine delivered intramuscularly, and recombinant L. monocytogenes delivered orally each individually have the ability to induce CD8+ and CD4+ T cell immune responses in a nonhuman primate. Four rhesus monkeys were immunized at weeks 0, 4, 8, and 12 with the pCSIVgag and pCSIVenv DNA plasmids and boosted with SIV expressing L. monocytogenes vaccines at weeks 16, 20, and 28. Four rhesus monkeys received only the L. monocytogenes vaccines at weeks 16, 20, and 28. A final group of monkeys served as a control group. Blood samples were taken before vaccination and 2 weeks post each injection and analyzed by ELISPOT for CD4+ and CD8+ T cell responses. Moderate vaccine induced SIV-specific cellular immune responses were observed following immunization with either DNA or L. monocytogenes vectors. However, the SIV antigen-specific immune responses were significantly increased when Rhesus macaques were primed with SIV DNA vaccines and boosted with the SIV expressing L. monocytogenes vectors. In addition, the combined vaccine was able to impact SIV239 viral replication following an intrarectal challenge. This study demonstrates for the first time that oral L. monocytogenes can induce a cellular immune response in a nonhuman primate and is able to enhance the efficacy of a DNA vaccine as well as provide modest protection against SIV239 challenge.

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

“…Indeed, a previous macaque study found no boosting of Tcell responses following a 3 rd immunization using SIV gag and env-encoding Lm; while antiListeria antibody levels were not reported, the authors suggested that anti-vector immunity induced by the previous two immunizations prevented boosting of SIV antigen-specific responses [45]. In our study, we detected minimal induction of anti-vector antibodies in animals given Lmdd-gag or Lmdd orally.…”

“…Recently, Boyer et al tested recombinant Lm as part of a vaccine regimen in macaques [45]. The Lm vectors were modified to secrete SIV Gag and Env.…”

Human Immunodeficiency Virus Type 1 Vaccine Development: Recent Advances in the Cytotoxic T-Lymphocyte Platform “Spotty Business”

“…A recombinant strain of Listeria monocytogenes has many promising features as a vaccine vector, including a natural tropism for mucosal tissues, an ability to infect APCs, a high level of CD8 ϩ T-cell induction, a low prevalence of preexposure in humans, and ease of manipulation and production in culture (reviewed in reference 90). Two independent studies performed with rhesus macaques illustrated the induction of mucosal cellular immune responses with a DNA prime and a Listeria boost, both encoding SIV Gag and Env (26,109). In a study performed by Boyer et al (26), the macaques that received the DNA prime-Listeria boost had better protection against an intrarectal challenge of SIV239, measured by control of viral loads for a longer period of time.…”

“…Two independent studies performed with rhesus macaques illustrated the induction of mucosal cellular immune responses with a DNA prime and a Listeria boost, both encoding SIV Gag and Env (26,109). In a study performed by Boyer et al (26), the macaques that received the DNA prime-Listeria boost had better protection against an intrarectal challenge of SIV239, measured by control of viral loads for a longer period of time. Neeson et al (109) further examined the induction of a mucosal SIV Gag-specific cellular immune response by the DNA prime-Listeria boost by demonstrating that Gag-specific CD8 ϩ T cells in the peripheral blood coexpress the gut-homing marker B7 in the peripheral blood and home to gut mucosal tissues.…”

Stimulation History Dictates Memory CD8 T Cell Phenotype: Implications for Prime-Boost Vaccination

“…The development of new vaccine regimens that more successfully establish protective CD8 T cell memory has proven challenging, but heterologous prime-boost schemes hold promise (3,4). This strategy involves sequential immunization with a common Ag incorporated into different vectors, such as DNA, vesicular stomatitis virus, poxviruses, adenoviruses, and Listeria monocytogenes (LM) 4 (3)(4)(5)(6)(7). Heterologous prime boosting results in larger numbers of Ag-specific memory CD8 T cells than achieved by a single vaccine administration or homologous boosting.…”