Flow cytometric analysis on reactivity of human T lymphocyte‐specific and cytokine‐receptor‐specific antibodies with peripheral blood mononuclear cells of chimpanzee (Pan troglodytes), rhesus macaque (Macaca mulatta), and squirrel monkey (Saimiri sciureus)

Ozwara, Hastings; Niphuis, Henk; Buijs, L; Jonker, Margreet; Heeney, Jonathan L.; Bambra, Charanjit S.; Thomas, Alan W.; Langermans, Jan A. M.

doi:10.1111/j.1600-0684.1997.tb00048.x

Cited by 20 publications

(20 citation statements)

References 13 publications

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“…The measurement of various cytokines in squirrel monkeys is not a sufficient measure of efficacy because they exhibit low levels of cross-reactivity with human cytokines. 35 Therefore, the interpretation of protective efficacy against malaria growth in terms of immunological responses is currently limited. Because the squirrel monkey is a valuable animal model for malaria vaccine development, the establishment of immunological analysis systems must provide more robust information for understanding the correlation between protective immunity and malaria infection.…”

Section: Animals Immunization and Infectionmentioning

confidence: 99%

TLR9 adjuvants enhance immunogenicity and protective efficacy of the SE36/AHG malaria vaccine in nonhuman primate models

Tougan

Aoshi

Coban

et al. 2013

Human Vaccines & Immunotherapeutics

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The SE36 antigen, derived from serine repeat antigen 5 (SERA5) of Plasmodium falciparum, is a promising blood stage malaria vaccine candidate. Ongoing clinical trials suggest the efficacy of the SE36 vaccine could be increased by the incorporation of more effective adjuvants into the vaccine formulation. In this study, we assessed the safety, immunogenicity and protective efficacy of SE36/AHG formulated with TLR9 ligand adjuvants K3 CpG oligodeoxyribonucleotides (CpG ODNs) (K3 ODN), D3 ODN or synthetic hemozoin, in two non-human primate models. SE36/AHG with or without each adjuvant was administrated to cynomolgus monkeys. A combination of TLR9 ligand adjuvant with SE36/AHG induced higher humoral and cellular immune response compared with SE36/AHG alone. Administration of a crude extract of P. falciparum parasite resulted in the induction of more SE36-specific IgG antibodies in monkeys vaccinated with a combination of SE36/AHG and adjuvant, as opposed to vaccination with SE36/AHG alone. The most effective TLR9 ligand, K3 ODN, was chosen for further vaccine trials in squirrel monkeys, in combination with SE36/AHG. All monkeys immunized with the combined SE36/AHG and K3 ODN formulation effectively suppressed parasitemia and symptoms of malaria following challenge infections. Furthermore, no serious adverse events were observed. Our results show that the novel vaccine formulation of K3 ODN with SE36/AHG demonstrates safety, potent immunogenicity and efficacy in nonhuman primates, and this vaccine formulation may form the basis of a more effective malaria vaccine.

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Section: Animals Immunization and Infectionmentioning

confidence: 99%

TLR9 adjuvants enhance immunogenicity and protective efficacy of the SE36/AHG malaria vaccine in nonhuman primate models

Tougan

Aoshi

Coban

et al. 2013

Human Vaccines & Immunotherapeutics

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“…Some studies on the basic immunological parameter in nonhuman primates have been reported [11,22,28,32,55]; formation on the phenotypic expression of some lymphocytic antigens in primates has been used to establish phylogenetic distances among different species [14,17,32,49] and to compare the ability of different monoclonal antibodies (mAbs) to identify homologous subsets of leukocytes in human beings and in nonhuman primates [39]. NK cells represent an important first line of defense against viral infections, against neoplastic cell growth, and in the control of hematopoiesis [1,13,46].…”

Section: Introductionmentioning

confidence: 99%

Comparative analysis of natural killer cell activity, lymphoproliferation and lymphocyte surface antigen expression in nonhuman primates housed at the CIRMF Primate Center, Gabon

Poaty‐Mavoungou

Onanga

Yaba

et al. 2001

J of Medical Primatology

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Six different species of nonhuman primates housed at the CIRMF Primate Center, cynomolgus monkeys (Macaca fascicularis), rhesus monkeys (Macaca mulatta), mandrills (Mandrillus sphinx), vervets (Cercopithecus aethiops pygerythrus), chimpanzees (Pan troglodyte) and baboons (Papio hamadryas), were evaluated for their natural killer cell activity and for the ability of their peripheral blood mononuclear cells to proliferate in response to known mitogens (concanavalin A, phytohemagglutinin and staphylococcal enterotoxin A) and to react with a panel of mouse monoclonal antibodies directed against human leukocyte surface antigens. Basic information on normal immune functions in these primates is important because of their use as experimental animal models for the study of human diseases such as acquired immunodeficiency syndrome (AIDS), hepatitis, loiasis and malaria.

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“…These antibodies cross-react with rhesus homologues. The number of CD64 ϩ MHC class II DR ϩ cells within the CD14 ϩ cell population was analyzed by FACS as previously described (34). knowlesi and that the gene was also present in parasites transfected with the integration construct.…”

Section: Parasitesmentioning

confidence: 99%

TransfectedPlasmodium knowlesiProduces Bioactive Host Gamma Interferon: a New Perspective for Modulating Immune Responses to Malaria Parasites

et al. 2003

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Transgenic pathogenic microorganisms expressing host cytokines such as gamma interferon (IFN-␥) have been shown to manipulate host-pathogen interaction, leading to immunomodulation and enhanced protection. Expression of host cytokines in malaria parasites offers the opportunity to investigate the potential of an immunomodulatory approach by generating immunopotentiated parasites. Using the primate malaria parasite Plasmodium knowlesi, we explored the conditions for expressing host cytokines in malaria parasites. P. knowlesi parasites transfected with DNA constructs for expressing rhesus monkey (Macaca mulatta) IFN-␥ under the control of the heterologous P. berghei apical membrane antigen 1 promoter, produced bioactive IFN-␥ in a developmentally regulated manner. IFN-␥ expression had no marked effect on in vitro parasite development. Bioactivity of the parasite-produced IFN-␥ was shown through inhibition of virus cytopathic effect and confirmed by using M. mulatta peripheral blood cells in vitro. These data indicate for the first time that it is feasible to generate malaria parasites expressing bioactive host immunomodulatory cytokines. Furthermore, cytokine-expressing malaria parasites offer the opportunity to analyze cytokine-mediated modulation of malaria during the blood and liver stages of the infection.Recombinant pathogenic microorganisms expressing host cytokines such as gamma interferon (IFN-␥) have been shown to modulate immune responses, leading to enhanced protection (15-17, 19, 35, 43, 47). Vaccinia virus and simian immunodeficiency viruses expressing a range of host cytokines were attenuated in vivo, leading to enhanced immune responses (15-17), and Leishmania major expressing host IFN-␥ was significantly attenuated in nude mice (47). These data indicate that in vivo expression of host cytokines by pathogens can manipulate the host-pathogen interaction and generate protective host responses. Thus far, expression of host cytokines by malaria parasites has not been examined. The development of transfection technology for malaria parasites (18,49,51,54) now enables expression of recombinant host proteins, such as cytokines in Plasmodium.IFN-␥ is one of the central effector cytokines in host response to malaria infection, especially during the liver stage (14,21,33,(38)(39)(40) and hence is attractive for expression in malaria parasites. In vitro and in vivo studies in rodent models of malaria have demonstrated that IFN-␥ plays a central role in protection against malaria liver-stage infection, possibly by inducing the infected hepatocyte to produce nitric oxide that kills parasites (31,33). In clinical vaccination studies with an attenuated sporozoite vaccine (reviewed in reference 32), vaccinated humans were protected from subsequent infection through IFN-␥-dependent responses. In separate studies in mice and monkeys, sterile protection was achieved through IFN-␥-dependent responses after exogenous treatment with interleukin-12 (IL-12) (21, 39). Studies using rodent and human malaria models have demon...

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Flow cytometric analysis on reactivity of human T lymphocyte‐specific and cytokine‐receptor‐specific antibodies with peripheral blood mononuclear cells of chimpanzee (Pan troglodytes), rhesus macaque (Macaca mulatta), and squirrel monkey (Saimiri sciureus)

Cited by 20 publications

References 13 publications

TLR9 adjuvants enhance immunogenicity and protective efficacy of the SE36/AHG malaria vaccine in nonhuman primate models

TLR9 adjuvants enhance immunogenicity and protective efficacy of the SE36/AHG malaria vaccine in nonhuman primate models

Comparative analysis of natural killer cell activity, lymphoproliferation and lymphocyte surface antigen expression in nonhuman primates housed at the CIRMF Primate Center, Gabon

TransfectedPlasmodium knowlesiProduces Bioactive Host Gamma Interferon: a New Perspective for Modulating Immune Responses to Malaria Parasites

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