Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-3 (of 3 Records) |
Query Trace: Promadej-Lanier N[original query] |
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Resistance to simian HIV infection is associated with high plasma interleukin-8, RANTES and Eotaxin in a macaque model of repeated virus challenges
Promadej-Lanier N , Hanson DL , Srinivasan P , Luo W , Adams DR , Guenthner PC , Butera S , Otten RA , Kersh EN . J Acquir Immune Defic Syndr 2010 53 (5) 574-81 Animal models for research on susceptibility to HIV are currently not available. Here we explore whether a macaque model of repeated low-dose rectal or vaginal virus challenges could be employed. We tested the hypothesis that susceptibility to Simian HIV is not merely stochastic in this model but rather is associated with identifiable host factors. Forty macaques required a median of 3.5 SHIVSF162P3 challenges for infection. We studied the association of their susceptibility with 13 predisposing plasma cytokines/chemokines (RANTES, Eotaxin, monocyte chemoattractant protein (MCP)-1, IL-7, MIP-1beta, TNF-alpha, MIP-1alpha, granulocyte colony-stimulating factor, IL-8, interferon-gamma, IL-17, IL-1beta, IL-6). Higher plasma RANTES, IL-8, and Eotaxin were associated with lower susceptibility, that is, higher resistance to infection. In a group of macaques with low IL-8 and RANTES, a median 3 exposures were required to infect; whereas, when either IL-8 or RANTES were high, a median 12 exposures were required. Thus, susceptibility was associated with identifiable discrete host factors and was not stochastic. In addition, the macaque model identified key human resistance factors (RANTES, Eotaxin), but also revealed a novel association with resistance (IL-8). Future direct evaluation of these or other factors in the animal model may be beneficial for developing new immunomodulation strategies for HIV prevention. |
Repeated rectal SHIVSF162P3 exposures do not consistently induce sustained T cell responses prior to systemic Infection in the repeat-low dose preclinical macaque model
Kersh EN , Luo W , Adams DR , Srinivasan P , Smith JM , Promadej-Lanier N , Ellenberger D , Garcia-Lerma JG , Butera S , Otten R . AIDS Res Hum Retroviruses 2009 25 (9) 905-17 The macaque model of repeated SHIV exposures is increasingly used as a preclinical tool to evaluate biomedical HIV intervention strategies. It is unclear whether multiple virus exposures induce immune responses in macaques, as documented in uninfected individuals repeatedly exposed to HIV. We here address whether repeated, rectal SHIV(SF162P3) exposures lead to systemic T cell activation in 12 rhesus macaques, and whether this is associated with increased infection resistance. Eight macaques became systemically infected after 2-7 exposures, three macaques were less susceptible (infection after 10-12 exposures), and one macaque remained uninfected after 14 exposures. PBMCs were retrospectively monitored for increases in T cell activation by analyzing the proportion of CD8(+) T cells, recently activated or proliferated T cells (markers CD38, Ki67), a marker for cytotoxicity (granzyme B), or T cell-produced plasma cytokines (IFN-gamma, RANTES, IL-2). Repeated virus exposures did not induce sustained, potent, or diverse T cell responses prior to systemic infection. Some changes occurred in the analyzed parameters during repeated virus exposures, but similar T cell activities were also observed in five SHIV-unexposed control macaques. Thus, we found no evidence that delayed infection or resistance to infection was associated with systemic, long-lasting, protective T cell responses to repeated rectal virus exposures. Our results provide further insights into the repeat exposure macaque model. We find that this model can be used for testing biomedical prevention strategies without concern of eliciting a systemic vaccination effect. |
Development and evaluation of a vaginal ring device for sustained delivery of HIV microbicides to non-human primates
Promadej-Lanier Nattawan , Smith James M , Srinivasan Priya , McCoy Clare F , Butera Sal , Woolfson ADavid , Malcolm RKarl , Otten Ron A . J Med Primatol 2009 38 (4) 263-271 BACKGROUND: There is considerable interest in developing coitally independent, sustained release formulations for long-term administration of HIV microbicides. Vaginal ring devices are at the forefront of this formulation strategy. METHODS: Non-medicated silicone elastomer vaginal rings were prepared having a range of appropriate dimensions for testing vaginal fit in pig-tailed and Chinese rhesus macaques. Cervicovaginal proinflammatory markers were evaluated. Compression testing was performed to compare the relative flexibility of various macaque and commercial human rings. RESULTS: All rings remaine d in place during the study period and no tissue irritation or significant induction of cervicovaginal proinflammatory markers or signs of physical discomfort were observed during the 8-week study period. CONCLUSIONS: Qualitative evaluation suggests that the 25 x 5-mm ring provided optimal fit in both macaque species. Based on the results presented here, low-consistency silicone elastomers do not cause irritation in macaques and are proposed as suitable materials for the manufacture of microbicide-loaded vaginal rings. |
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