Abstract：
:There is a logarithmic increase in the cost and complexity of the research and development process when transitioning a promising candidate vaccine from the laboratory into the clinic. Managing complex development programs involving people from diverse technical, cultural and geographical backgrounds is a specialised skill. It is essential that the group is clear on their objectives and how their activities affect others, that communication is open, inclusive and effective, and that the most rigorous, scientific approach based on statistical principles in compliance with regulatory requirements is used. Applying these standards to all vaccine development programs will filter out inappropriate candidates more readily and enhance the efficiency of vaccine development. The challenges of developing a new vaccine are illustrated in human immunodeficiency virus (HIV) vaccinology. Selecting vaccine candidates for HIV requires the ability to evaluate the large number of potential antigens in imperfect and non-standardised animal models. Further, using these models to evaluate questions such as dose scaling to humans, optimal route of administration, the use of adjuvants and potential formulation improvements adds variable to variable, making the interpretation of results particularly challenging. This may lead to the promotion of a poor candidate or the elimination of a good one. The absence of precise immunological correlates of protection and the prohibitive cost of confirmatory clinical trials are further significant barriers. However, there are practical steps that can be taken to standardise early vaccine evaluation, which would result in more efficient development of new vaccines for HIV and other disease areas with similarly challenging development issues (such as hepatitis C virus, influenza, Mycobacterium tuberculosis and malaria).
journal_name
Immunol Cell Bioljournal_title
Immunology and cell biologyauthors
Sullivan Mdoi
10.1038/icb.2009.30subject
Has Abstractpub_date
2009-07-01 00:00:00pages
366-70issue
5eissn
0818-9641issn
1440-1711pii
icb200930journal_volume
87pub_type
杂志文章,评审abstract：:Genetic fusion of tandem repeats of the complement molecule C3d has been shown to considerably enhance immune responses to genetic vaccines. We have investigated the applicability of this approach to augment humoral immune responses toward vaccines delivered by recombinant adeno-associated virus (AAV) vectors. C3d(3)-...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1038/icb.2009.92
更新日期：2010-02-01 00:00:00
abstract：:Granulocyte-macrophage colony-stimulating factor (GM-CSF) and urokinase-type plasminogen activator (uPA) can contribute to the progression of chronic inflammatory diseases with possible involvement of macrophages. In this study, we investigated the role of both GM-CSF and uPA in Porphyromonas gingivalis-induced experi...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1038/icb.2015.25
更新日期：2015-09-01 00:00:00
abstract：:Active Brugia pahangi microfilariae (Mf) were injected into naive male BALB/c mice intraperitoneally. Microfilaraemia was studied for 28 days; and Mf circulated in blood in optimum numbers from 3 to 14 days. Anti-Mf response was assessed by the rate of disappearance of Mf from blood as well as their absence from visce...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1038/icb.1988.43
更新日期：1988-10-01 00:00:00
abstract：:Genetic variants of interleukin 2 (IL-2) and its receptor are associated with murine and human susceptibility to Type 1 diabetes, yet the role of IL-2 in controlling pancreatic islet-reactive T cells is unknown. Here, we develop a model where IL-2 deficiency precipitates a breakdown of self-tolerance and progression t...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1038/sj.icb.7100049
更新日期：2007-06-01 00:00:00
abstract：:The immune system has developed mechanisms to detect and initiate responses to a continual barrage of immunological challenges. Dendritic cells (DC), a heterogeneous population of leucocytes, play a major role as immunosurveillance agents. To accomplish this function, DC are equipped with highly efficient mechanisms t...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1111/j.1440-1711.2004.01216.x
更新日期：2004-02-01 00:00:00
abstract：:Two related folate antagonists aminopterin (AMN) and methotrexate (MTX) were used to produce drug-antibody conjugates and their tumouricidal effects compared in vitro and in vivo. Active ester derivatives were produced with the use of N-hydroxysuccinimide (NHS) and covalently coupled to monoclonal antibodies (MoAb) re...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1038/icb.1987.57
更新日期：1987-12-01 00:00:00
abstract：:A long-term culture (LTC) system has been established that supports the continuous production of dendritic cells (DC) from haemopoietic cells present in the culture. The production of cells depends on the presence of an intact stromal cell layer containing a mixture of fibroblasts and endothelial cells. Cells are shed...
journal_title：Immunology and cell biology
pub_type： 杂志文章,评审
doi：10.1046/j.1440-1711.1999.00851.x
更新日期：1999-10-01 00:00:00
abstract：:The CD8 co-receptor engages peptide-major histocompatibility complex class I (pMHCI) molecules at a largely invariant site distinct from the T-cell receptor (TCR)-binding platform and enhances the sensitivity of antigen-driven activation to promote effective CD8+ T-cell immunity. A small increase in the strength of th...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1038/icb.2016.85
更新日期：2017-01-01 00:00:00
abstract：:Sustained-release vaccine delivery systems may enhance the immunogenicity of subunit vaccines and reduce the need for multiple vaccinations. The aim of this study was to develop a thermoresponsive hydrogel using poloxamer 407-chitosan (CP) grafted copolymer as a delivery system for single-shot sustained-release vaccin...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1111/imcb.12031
更新日期：2018-07-01 00:00:00
abstract：:The recognition of T cell receptors (TCR) by purified major histocompatibility complex (MHC) class II-peptide complexes in the absence of costimulatory signals leads to the induction of T cell non-responsiveness or anergy. In a recent study using human T cell clones, it was observed that prolonged incubation of restin...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1038/icb.1996.13
更新日期：1996-02-01 00:00:00
abstract：:The NK gene complex (NKC) on mouse chromosome 6 encodes receptors that are expressed on NK cells, such as Ly49H, and is involved in regulating NK cell control of virus infections, such as murine cytomegalovirus (MCMV). In the present study, we investigated the level of allelic heterogeneity in NKC loci in populations ...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1111/j.1440-1711.2005.01311.x
更新日期：2005-04-01 00:00:00
abstract：:Spleen cells from newborn mice are immunologically nonreactive and do not respond by proliferation upon stimulation with the T cell mitogen concanavalin-A (Con-A) or with recombinant interleukin-2 (IL-2). We have found that, in spite of the observed non-reactivity in the proliferative tests, cells from newborn mice we...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1038/icb.1991.59
更新日期：1991-12-01 00:00:00
abstract：:The Australian populations of rainbow trout (Onchorhynchus mykiss) and Atlantic salmon (Salmo salar) were found to have similar immunological responses to local strains of Vibrio anguillarum as those reported for the more genetically diverse populations of these fish and strains of V. anguillarum found in the Northern...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1038/icb.1992.51
更新日期：1992-12-01 00:00:00
abstract：:T-cell repertoire is selected according to self peptide-MHC (major histocompatibility complex) complexes in the thymus. Although most peripheral T cells recognize specific pathogen-derived peptides complexed to self-MHC exclusively, some possess cross-reactivity to other self or foreign peptides presented by self-MHC ...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1038/icb.2014.113
更新日期：2015-05-01 00:00:00
abstract：:Latex beads, 250 and 610 nm in diameter, and parapox virus isolated from ecthyma in sheep, were injected into intestinal loops containing either jejunal or ileal Peyer's patches (PP) of 3-4 week old calves. Uptake of latex and parapox virus was restricted to the ileal PP, 30-60 min after injection. The latex beads see...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1038/icb.1988.35
更新日期：1988-08-01 00:00:00
abstract：:The glycoprotein processing inhibitor castanospermine (CS) and the monosaccharide mannose-6-phosphate (M6P), as well as some sulfated polysaccharides (SPS), have been shown to inhibit inflammation in rat models of experimental autoimmune encephalomyelitis and adjuvant-induced arthritis. Here, the anti-inflammatory eff...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1038/icb.1994.55
更新日期：1994-10-01 00:00:00
abstract：:Mycobacterial disease remains a serious global health problem. Tuberculosis causes more than 2 million deaths a year, and leprosy is still a cause of severe disability in many parts of the world. As a result of the study of individuals with marked susceptibility to usually nonpathogenic mycobacteria, as well as case-c...
journal_title：Immunology and cell biology
pub_type： 杂志文章,评审
doi：10.1111/j.1440-1711.2006.01420.x
更新日期：2006-04-01 00:00:00
abstract：:The Kunjin replicon was used to express a polytope that consisted of seven hepatitis C virus cytotoxic T lymphocyte epitopes and one influenza cytotoxic T lymphocyte epitope for vaccination studies. The self-replicating nature of, and expression from, the ribonucleic acid was confirmed in vitro. Initial vaccinations w...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1046/j.0818-9641.2002.01137.x
更新日期：2003-02-01 00:00:00
abstract：:There is a need for non-living adjuvant vectors that will allow a full range of local and systemic immune responses to orally administered purified antigens. Here we describe our experience with lipophilic immune-stimulating complexes (ISCOMs) containing the saponin adjuvant Quil A. When given orally, ISCOMs containin...
journal_title：Immunology and cell biology
pub_type： 杂志文章,评审
doi：10.1046/j.1440-1711.1998.00749.x
更新日期：1998-06-01 00:00:00
abstract：:Concanavalin A (Con A)-induced hepatitis is thought to be a T-cell-mediated disease with active destruction of liver cells. Interleukin (IL)-17 is a cytokine produced principally by CD4(+) T cells. However, whether IL-17/IL-17 receptor (IL-17/IL-17R)-mediated responses are involved in T-cell-mediated Con A-induced liv...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1038/icb.2011.59
更新日期：2012-04-01 00:00:00
abstract：:Neospora caninum is a coccidian parasite causative of clinical infections in a wide range of animal hosts. The maturation and activation of splenic conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) were studied here in BALB/c mice challenged intraperitoneal with N. caninum tachyzoites. The nu...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1038/icb.2009.65
更新日期：2010-01-01 00:00:00
abstract：:The surface phenotype of T cells reflects both their relative maturity and their activation state. To determine the pattern of surface markers characteristic of activated T cells, purified mature T cells were stimulated in vitro for periods of 0.5-5 days with Concanavalin-A (Con-A) or phorbol myristic acetate (PMA) an...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1038/icb.1988.39
更新日期：1988-08-01 00:00:00
abstract：:Lethal giant larvae-1 (Lgl-1) is an evolutionary conserved protein that regulates cell polarity in diverse lineages; however, the role of Lgl-1 in the polarity and function of immune cells remains to be elucidated. To assess the role of Lgl-1 in T cells, we generated chimeric mice with a hematopoietic system deficient...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1038/icb.2015.82
更新日期：2016-03-01 00:00:00
abstract：:A murine monoclonal antibody has been used to characterise a 45,000 Da antigen that is associated with the surface membrane of merozoites of the human malaria parasite Plasmodium falciparum. The antigen is a glycoprotein and incorporates myristic acid. ...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1038/icb.1987.48
更新日期：1987-10-01 00:00:00
abstract：:The present paper describes a comparative analysis of light chains associated with primary and secondary IgM, as well as with secondary IgG antibodies to fluorescein, undertaken in order to explore the relationship between light chain somatic hypermutation and the isotype switch. The data reveal a disparity in the fre...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1046/j.1440-1711.2000.00903.x
更新日期：2000-06-01 00:00:00
abstract：:Non-toxic agents that target intracellular signalling pathways in apoptosis may have potential therapeutic use in many diseases. One such agent is the transition metal Zn, a dietary cytoprotectant and anti-oxidant, which stimulates cell proliferation and suppresses apoptosis. Zn is maintained in discrete subcellular p...
journal_title：Immunology and cell biology
pub_type： 杂志文章,评审
doi：10.1046/j.1440-1711.1999.00825.x
更新日期：1999-06-01 00:00:00
abstract：:As host immunological defenses are impaired during HIV infection, it is difficult to elicit good responses when attempting to develop therapeutic vaccines against HIV. To try to solve this situation, adjuvants, particularly cytokines, are currently under evaluation. Owing to the fact that adenosine deaminase (ADA) is ...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1038/icb.2009.53
更新日期：2009-11-01 00:00:00
abstract：:Plasma cells play a pivotal role in the immune system and are responsible for the synthesis and release of immunoglobulins. Numerous in vitro culture experiments on the yolk sac demonstrated the generation of mature cells of the myeloid and lymphoid lineages under appropriate culture conditions. However, there are no ...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1046/j.1440-1711.2003.t01-1-01178.x
更新日期：2003-10-01 00:00:00
abstract：:Immunotherapy of tumours using T cells expanded in vitro has met with mixed clinical success suggesting that a greater understanding of tumour/T-cell interaction is required. We used a HPV16E7 oncoprotein-based mouse tumour model to study this further. In this study, we demonstrate that a HPV16E7 tumour passes through...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1111/j.0818-9641.2004.01273.x
更新日期：2004-10-01 00:00:00
abstract：:Interleukin (IL)-9-producing CD4(+) T cells are a novel subset of T helper (Th) cells that develops independently of the Th1, Th2, Th17 and regulatory T-cell lineages. Similar to the murine model, transforming growth factor (TGF)-beta and IL-4 directed human naive CD4(+) T cells to produce IL-9. Whereas IL-4 suppresse...
journal_title：Immunology and cell biology
pub_type： 杂志文章
doi：10.1038/icb.2010.53
更新日期：2010-08-01 00:00:00
