F C Jensen — Page 5 | PubMed Health

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CXCR4 and CCR5 expression on CD4+ T cells in vivo and HIV-1 antigen beta-chemokine production in vitro after treatment with HIV-1 immunogen (REMUNE).

BACKGROUND: The chemokine receptors CXCR4 and CCR5 have been identified as the major coreceptors for HIV-1 on CD4+ cells and macrophages. The natural ligands for these receptors are SDF-1 and the beta-chemokines (MIP-1alpha, MIP-1beta, RANTES), respectively, and are the products of a variety of immune cells, including CD8+ T lymphocytes. STUDY DESIGN/METHODS: We hypothesized that the ability to stimulate the natural ligands for these receptors using an immune based therapy might influence in vivo chemokine receptor expression. RESULTS: In vivo CXCR4 expression remained stable after treatment with an HIV-1 Immunogen (REMUNE), whereas CCR5 expression on CD4+ T cells decreased (p < .05). Furthermore, HIV-1 antigen-specific production of beta-chemokines in vitro was also augmented (P < .05). CONCLUSIONS: These preliminary results suggest that this HIV-1-specific immune-based therapy can stimulate antigen-specific beta-chemokine production in vitro and downregulate CCR5 receptor expression on CD4 cells in vivo.

AIDS Vaccines↗

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Human immunodeficiency virus (HIV)-specific immune responses are generated with the simultaneous vaccination of a gp120-depleted, whole-killed HIV-1 immunogen with cytosine-phosphorothioate-guanine dinucleotide immunostimulatory sequences of DNA.

OBJECTIVES: We compared the effect of priming with a synthetic oligodeoxynucleotide (ODN) immunostimulatory DNA sequence followed by vaccination with human immunodeficiency virus type 1 (HIV-1) in incomplete Freund's adjuvant (IFA) or HIV-1 antigen alone to the simultaneous administration of immunostimulatory sequences (ISS) with HIV-1 in IFA. METHODS: We examined immune function involving interferon-gamma (IFN-gamma) production, RANTES (regulated upon activation, normal T cell expressed and secreted) production, and lymphocyte proliferation, all of which appear to be augmented in HIV-1-exposed, but uninfected, individuals. RESULTS: We demonstrate that similar levels of antigen-specific IFN-gamma were produced from lymph node cells of the animals immunized with HIV-1 antigen in IFA containing the CpG ODN 1826 (ISS; mean +/- SE = 450.8 +/- 224.3 pg/mL) and the group of animals primed with the ODN before injection with the HIV-1 in IFA (mean +/- SE = 377.7 +/- 294.8 pg/mL) or HIV-1 antigen alone (IFN-gamma = 0 pg/mL). However, the group that received the HIV-1 in IFA plus ISS mounted a stronger lymphocyte proliferation (mean net +/- SE = 29,180 +/- 1,932 cpm) compared to the group primed with the ODN before injection with HIV-1 in IFA (mean net +/- SE = 8,575 +/- 2,978 cpm). Furthermore, the group that received the HIV-1 in IFA plus ISS also mounted stronger beta-chemokine production measured as RANTES (mean +/- SE = 1,217 +/- 267.4 pg/mL) compared to the group that received the ODN before injection with HIV-1 in IFA (mean +/- SE = 129.1 +/- 48.5 pg/mL). Antibody responses from the group that received the HIV-1 in IFA plus ISS also showed a higher p24-specific response that was predominantly of the immunoglobulin G IgG2b isotype. CONCLUSION: These results suggest that the simultaneous administration of the ISS in the HIV-1 in IFA emulsion may be a condidate for testing in non-human primates and in human studies as a therapeutic and preventative vaccine.

AIDS Vaccines↗