A Formalin-Inactivated Whole SIV Vaccine Confers Protection in Macaques

Murphey‐Corb, Michael; Martin, Louis N.; Davison-Fairburn, Billie; Montelaro, Ronald C.; Miller, Mark A.; West, Melanie; Ohkawa, Susumu; Baskin, Gary B.; Zhang, Jing Yu; Putney, Scott D.; Allison, A. C.; Eppstein, Deborah A.

doi:10.1126/science.2555923

Cited by 394 publications

(179 citation statements)

References 27 publications

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“…Schnittman et al (1990) suggested that the decline ofCD29+ cells in HIV positive individuals was due to the preferential replication of HIV in these cells. A very early loss ofCD29+CD4+ cells from the blood ofSIVsm infected macaques has also been noted by Murphey-Corb et al (1989). The low level of CD29+CD8+ cells in blood and spleen ofthe animal sacrificed 6 weeks post infection was not seen in the other monkeys at later times.…”

Section: Discussionmentioning

confidence: 60%

Early phenotypic and functional alterations in lymphocytes from simian immunodeficiency virus infected macaques

Kneitz

Kerkau

Müller

et al. 1993

Veterinary Immunology and Immunopathology

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Kneitz, c., Kerkau, T., Müller, J., Coulibaly, C., Stahl-Hennig, c., Hunsmann, G., Hünig, T. and Schimpl, A., 1993. Early phenotypic and functional alterations in Iymphocytes from simian immunodeficiency virus infected macaques. Veto Immunol. Immunopathol., Phenotypic and functional changes in Iymphocytes from rhesus monkeys (Macaca mulatta) were investigated during the first 6 months after infection with SIVmac 32H. Animals preimmunized with keyhole !impet hemocyanin (KLH) were sacrificed 1. 3, 6, 12, and 24 weeks post infection. Subset composition and function oflymphocytes from blood, spleen, Iymph node and thymus were analysed. In addition to a rapid decline in CD4/CD8 ratios, a massive reduction in CD29+CD4+ cells was seen in the periphery. Although depletion of this subset was observed throughout the course of this experiment, the loss of proliferative T cell responses was most pronounced very early after infection and partially recovered after Month 3. Polyclonal cytotoxic responses were only slightly affected. In the thymus, a gradual, but moderate loss of CD4 + CD8 + immature thymocytes, and a relative increase in both CD4 + and CD8 + mature subsets was observed. Infectious virus was readily reeovered from homogenates oflymph node and spleen, but not of thymus tissue. Interestingly, however, virus was deteeted in thymocytes from a11 infected animals by cocultivation with a simian immunodeficiency virus (SIV) susceptible celliine. ABBREVIATIONSAb, antibody; BSA, bovine serum albumin; BSS, balaneed salt solution; DN, double negative; DP, double positive; FCS, fetal calf serum; KLH, keyhole Iimpet hemocyanin; mAb, monoc1onal antibody, PBL, peripheral blood Iymphoeyte; PBS, phosphate buffered saline; SIV, simian immunodeficieney virus; SP, single positive.

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Section: Discussionmentioning

confidence: 60%

Early phenotypic and functional alterations in lymphocytes from simian immunodeficiency virus infected macaques

Kneitz

Kerkau

Müller

et al. 1993

Veterinary Immunology and Immunopathology

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“…In the past three decades, a large literature has demonstrated that muramyl peptides display a number of antiviral activities in vitro and in vivo, against microbes such as influenza, herpes simplex or human immunodeficiency viruses [29][30][31]. However, the mechanisms by which these muramyl peptides display antiviral properties remain poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Nod1 and Nod2 induce CCL5/RANTES through the NF‐κB pathway

et al. 2007

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The Nod-like receptor proteins Nod1 and Nod2 participate in innate immune responses against bacteria through intracellular detection of peptidoglycan, a component of bacterial cell wall. Recent evidence has demonstrated that Nod1 stimulates the release of chemokines that attract neutrophils at the site of infection, such as CXCL8/IL-8 in humans, and CXCL1/keratinocyte-derived chemokine and CXCL2/MIP-2 in mice. We aimed to determine whether Nod proteins could trigger the release of CCL5/RANTES, a chemokine known to attract a number of immune cells, but not neutrophils. Our results demonstrate that activation of both Nod1 and Nod2 results in substantial secretion of CCL5 by murine macrophages. Moreover, in vivo, the intraperitoneal injection of murine Nod1 or Nod2 agonists resulted in a rapid secretion of CCL5 into the bloodstream. We also observed that Nod-dependent secretion of CCL5 did not correlate with the induction of the interferon-b pathway, a major signaling cascade for the activation of CCL5 by viruses. In contrast, we identified a key role of the NF-jB pathway in Noddependent stimulation of the CCL5 promoter. Together, these results identify a novel target downstream of Nod1 and Nod2, which is likely to play a key role in orchestrating the global Nod-dependent immune defense during bacterial infections.

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“…simian acquired immune deficiency syndrome (52). SIV (53) , and a recombinant HIV-1 vaccine in chimpanzees (54). In the absence of an efficacious adjuvant, little or no protection is observed.…”

Section: Use Of Adjuvants In Vaccinesmentioning

confidence: 99%

Adjuvants for a New Generation of Vaccines

Allison¹,

Byars²

1992

Canadian Journal of Infectious Diseases

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for a new generation of vaccines. Can J Infect Dis 1992;3(Suppl B):84B-93B. Subunit antigens of viruses and other infectious agents in their natural configuration can be produced by recombinant DNA technology. To elicit protective immunity such antigens have to be admirustered with adjuvants that elicit cell-mediated immunity, including genetically restricted cytotoxicity, and that pr oduce high alfmity antibodies of protective isotypes. Antibodies of such isotypes (immunoglobulin G2a [IgG2a] in the mouse and IgG I in humans) efficiently activate complement and eiTect antibody-dependent cell-mediated cytotoxicity. Naturally occurring adjuvants such as lipopolysaccharide and muramyl dipeptide (MOP) are pyrogenic and produce uveitis and arthritis in susceptible experimental animal and human recipients. Synthetic analogues of MOP and monophosphoryl lipid A (MPL) retain adjuvant activity with reduced side eiTects. Adjuvants increase the expression of class II major histocompatibility complex on antigen-presenting cells and cytokine production: interferon-gamma augments the production of IgG2a antibod ies in the mouse. Dispersion of antigens in water-oil emulsions, immunestimulating complexes or liposomes also increases immunogenicity. at least partly by targeting antigens to antigen-presenting cells. Inclusion of MOP analogues or MPL in such systems constitutes adjuvant formu lations. such as MOP-A. When used with a variety of recombinant and other subunit antigens. such adjuvants elicit protective immunity in experimental animals. This strategy improves vaccines already in use (eg, inJl uenza and hepatitis B) and makes possible new vaccines (herpesviruses, simian and human immunodeficiency viruses. respiratory syncytial virus and acellular pertussis).

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A Formalin-Inactivated Whole SIV Vaccine Confers Protection in Macaques

Cited by 394 publications

References 27 publications

Early phenotypic and functional alterations in lymphocytes from simian immunodeficiency virus infected macaques

Early phenotypic and functional alterations in lymphocytes from simian immunodeficiency virus infected macaques

Nod1 and Nod2 induce CCL5/RANTES through the NF‐κB pathway

Adjuvants for a New Generation of Vaccines

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