Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid.

Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 422 Curie Boulevard, Philadelphia, PA 19104, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 12/2007; 104(47):18648-53. DOI: 10.1073/pnas.0709198104
Source: PubMed

ABSTRACT The cell-mediated immune profile induced by a recombinant DNA vaccine was assessed in the simian/HIV (SHIV) and macaque model. The vaccine strategy included coimmunization of a DNA-based vaccine alone or in combination with an optimized plasmid encoding macaque IL-15 (pmacIL-15). We observed strong induction of vaccine-specific IFN-gamma-producing CD8(+) and CD4(+) effector T cells in the vaccination groups. Animals were subsequently challenged with 89.6p. The vaccine groups were protected from ongoing infection, and the IL-15 covaccinated group showed a more rapidly controlled infection than the group treated with DNA vaccine alone. Lymphocytes isolated from the group covaccinated with pmacIL-15 had higher cellular proliferative responses than lymphocytes isolated from the macaques that received SHIV DNA alone. Vaccine antigen activation of lymphocytes was also studied for a series of immunological molecules. Although mRNA for IFN-gamma was up-regulated after antigen stimulation, the inflammatory molecules IL-8 and MMP-9 were down-regulated. These observed immune profiles are potentially reflective of the ability of the different groups to control SHIV replication. This study demonstrates that an optimized IL-15 immune adjuvant delivered with a DNA vaccine can impact the cellular immune profile in nonhuman primates and lead to enhanced suppression of viral replication.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Human immunodeficiency virus type 1 and malaria are co-endemic in many areas. We evaluated the effects of Plasmodium inui infection on the performance of a simian immunodeficiency virus (SIV) DNA vaccine. Rhesus macaques were infected with P. inui by transfusion of whole blood from a persistently infected animal. Animals with and animals without P. inui infection were then vaccinated 4 times with an SIV DNA vaccine encoding SIVgag, SIVpol, and SIVenv. Animals were subsequently challenged with thirty 50% rhesus monkey infectious doses of SIVmac251 6 weeks after the last vaccination. P. inui-infected immunized animals showed a significantly higher viral load than animals without P. inui infection (P = .010, by the Wilcoxon rank sum test). The higher viral loads in the P. inui-infected animals were durable and were observed at all sampling time points across the study (P = .00245, by the Wilcoxon rank test). The P. inui-infected animals also had correspondingly lower CD4(+) cell counts. There were fewer vaccine-specific CD4(+) and CD8(+) cells in the P. inui-infected animals, compared with uninfected animals. Of importance, P. inui infection seemed to decrease the number of CD8(+) cells that could proliferate or secrete interferon γ, although the number of CD8(+) cells capable of secreting tumor necrosis factor α following in vitro stimulation was increased. This study demonstrated that P. inui infection had an influence on the immune response to an SIV DNA vaccine and decreased the vaccine's efficacy.
    The Journal of Infectious Diseases 06/2012; 206(4):523-33. · 5.85 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Numerous studies have characterized the cytokine modulation observed in human immunodeficiency virus (HIV) infected individuals, from initial infection through chronic disease. Progressive and non-progressive HIV infection models show the cytokine milieu differs in terms of production and responsiveness in these two groups, suggesting an understanding of the role cytokines play during infection is necessary for directing the immune response toward viral control. This review will cover cytokine induction and dysfunction during HIV pathogenesis, with a focus on the interplay between cytokines and transcription factors, T cell activation, and exhaustion. We highlight cytokines that have either vaccine adjuvant or therapeutic potential and discuss the need to identify key factors required for prevention of progression, clearance of infection, or protection from acquisition.
    Cytokine & growth factor reviews 06/2012; 23(4-5):181-91. · 6.49 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Chikungunya virus (CHIKV) is an important emerging mosquito-borne alphavirus, indigenous to tropical Africa and Asia. It can cause epidemic fever and acute illness characterized by fever and arthralgias. The epidemic cycle of this infection is similar to dengue and urban yellow fever viral infections. The generation of an efficient vaccine against CHIKV is necessary to prevent and/or control the disease manifestations of the infection. In this report, we studied immune response against a CHIKV-envelope DNA vaccine (pEnv) and the role of the CHIKV nonstructural gene 2 (nsP2) as an adjuvant for the induction of protective immune responses in a relevant mouse challenge model. When injected with the CHIKV pEnv alone, 70% of the immunized mice survived CHIKV challenge, whereas when co-injected with pEnv+pnsP2, 90% of the mice survived viral challenge. Mice also exhibited a delayed onset signs of illness, and a marked decrease in morbidity, suggesting a nsP2 mediated adjuvant effect. Co-injection of the pnsP2 adjuvant with pEnv also qualitatively and quantitatively increased antigen specific neutralizing antibody responses compared to vaccination with pEnv alone. In sum, these novel data imply that the addition of nsP2 to the pEnv vaccine enhances anti-CHIKV-Env immune responses and maybe useful to include in future CHIKV clinical vaccination strategies.
    Viral immunology 02/2013; 26(1):75-83. · 1.78 Impact Factor

Full-text (2 Sources)

Available from
May 19, 2014