HLA-E: exploiting pathogen-host interactions for vaccine development

Sharpe, Hannah; Bowyer, Georgina; Brackenridge, Simon; Lambe, Teresa

doi:10.1111/cei.13292

Cited by 33 publications

(36 citation statements)

References 101 publications

(224 reference statements)

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“…The macaque MHC-E molecules present identical SIV-derived peptides to MHC-E–restricted CD8+ T cells, leading to allogeneic and cross-species peptide recognition of MHC-E presented epitopes [181]. The functional similarity between human MHC-E and their macaque orthologs reinforces the argument supporting the relevance of macaque models (the rhesus monkey and the cynomolgus macaque) in the study of HLA-E in the fight against infectious pathogens [160].…”

Section: Roles Of Mafa-e In Experimental Medicinementioning

confidence: 97%

“…The latter play a crucial role in the regulation of immune functions, and particularly in the activation of NK cells by their interaction with KIR and LILR receptors. The functional roles of these non-classical class I HLA proteins in the development of pregnancy, cancers, infectious diseases have recently been reviewed [157,158,159,160]. We have already indicated that the Mafa -E, Mafa -F genes, are found in all MHC macaque haplotypes and have low polymorphism, similarly to all other non-human primates.…”

Section: Interactions Between Mhc Proteins and Various Receptors:mentioning

confidence: 99%

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The Cynomolgus Macaque MHC Polymorphism in Experimental Medicine

Shiina

Blancher

2019

Cells

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Among the non-human primates used in experimental medicine, cynomolgus macaques (Macaca fascicularis hereafter referred to as Mafa) are increasingly selected for the ease with which they are maintained and bred in captivity. Macaques belong to Old World monkeys and are phylogenetically much closer to humans than rodents, which are still the most frequently used animal model. Our understanding of the Mafa genome has progressed rapidly in recent years and has greatly benefited from the latest technical advances in molecular genetics. Cynomolgus macaques are widespread in Southeast Asia and numerous studies have shown a distinct genetic differentiation of continental and island populations. The major histocompatibility complex of cynomolgus macaque (Mafa MHC) is organized in the same way as that of human, but it differs from the latter by its high degree of classical class I gene duplication. Human polymorphic MHC regions play a pivotal role in allograft transplantation and have been associated with more than 100 diseases and/or phenotypes. The Mafa MHC polymorphism similarly plays a crucial role in experimental allografts of organs and stem cells. Experimental results show that the Mafa MHC class I and II regions influence the ability to mount an immune response against infectious pathogens and vaccines. MHC also affects cynomolgus macaque reproduction and impacts on numerous biological parameters. This review describes the Mafa MHC polymorphism and the methods currently used to characterize it. We discuss some of the major areas of experimental medicine where an effect induced by MHC polymorphism has been demonstrated.

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Section: Roles Of Mafa-e In Experimental Medicinementioning

confidence: 97%

Section: Interactions Between Mhc Proteins and Various Receptors:mentioning

confidence: 99%

The Cynomolgus Macaque MHC Polymorphism in Experimental Medicine

Shiina

Blancher

2019

Cells

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“…Nevertheless, one should not dismiss the findings from the RhCMV model as irrelevant for the human situation. HLA-II restricted CD8 T-cell responses to natural HIV infections are rare but present in humans [159] and HLA-E-restricted induction of adaptive responses to infections is an exciting area of rapid advances [160,161]. Some HIV-derived peptides are loaded on HLA-E molecules [162] and the variability of HLA-E binding peptides seems to be due to structural characteristics of its peptide pocket malleability [163].…”

Section: Unconventional Mhc Restrictionmentioning

confidence: 99%

Vaccine Vectors Harnessing the Power of Cytomegaloviruses

2019

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Cytomegalovirus (CMV) species have been gaining attention as experimental vaccine vectors inducing cellular immune responses of unparalleled strength and protection. This review outline the strengths and the restrictions of CMV-based vectors, in light of the known aspects of CMV infection, pathogenicity and immunity. We discuss aspects to be considered when optimizing CMV based vaccines, including the innate immune response, the adaptive humoral immunity and the T-cell responses. We also discuss the antigenic epitopes presented by unconventional major histocompatibility complex (MHC) molecules in some CMV delivery systems and considerations about routes for delivery for the induction of systemic or mucosal immune responses. With the first clinical trials initiating, CMV-based vaccine vectors are entering a mature phase of development. This impetus needs to be maintained by scientific advances that feed the progress of this technological platform.Vaccines 2019, 7, 152 2 of 28 CMV-based vaccines, the large pool of functional antigen-specific T cells in the periphery and the possibility to modify CMV genomes due to improvements in viral genetics [11] draw a strong interest to CMV as a vaccine vector [12,13] (Table 1). The inflationary response appears linked to immune protection [14,15] and has been proposed as a target for immunization induction [16]. Vaccines 2019, 7, 152 3 of 28 Full-length HPV16 E6 and E7 Antigen fused to the C-terminus of ie2 Transient limitation of tumour cell growth MCMV IE2E7 [14] MHC-I restricted HPV16 E7 49-57 epitope Epitope fused to the C-terminus of ie2 No tumour cell growth upon challenge MCMV-M79-FKBP-E7 [36] MCMV Smith Strain with FKBP-mediated destabilization of the essential M79 gene Vaccines 2019, 7, 152 5 of 28Besides the exceptional induction of adaptive immune response in humans [2,37], CMV possesses assets that conveniently address weaknesses common to other vector candidates. The cloning of CMV genomes as bacterial artificial chromosomes in Escherichia coli [38] has allowed genetic engineering approaches to effectively express multiple exogenous immunogens or modify large genome portions [39,40]. Furthermore, CMV is known to superinfect hosts with a history of prior exposure to the virus [41] due to its immune evasive properties that protect the virus from recognition by primed T-cells [42] and CMV vectors induce protective immunity in experimentally vaccinated animals with documented prior exposure to 36]. Therefore, CMV vector candidates would avoid immune interference as described for AdV. CMV is a pathogenic organism in immunodeficient populations [43] or in congenitally infected children. Therefore, it is imperative for any HCMV vaccine vector to be attenuated. The generation of replication deficient CMVs that maintain their immunogenicity [36,44] and the modification of genome portions that contain evasions genes [45], as well as the insertion of activating ligands to increase immune control of CMV [46][47][48] are strategies that will be described in this review. Inter...

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“…Understanding the interaction of the host with a viral pathogen to expedite vaccine development is a theme taken up in the review contributed by Sharpe et al . Specifically, they address the targeting of the human leucocyte antigen (HLA)‐E molecule, a major histocompatibility complex (MHC)1b molecule, by viral vectors to induce non‐classical CD8 + T cell immunity and to inhibit natural killer (NK) cell activity.…”

mentioning

confidence: 99%

Vaccines for emerging pathogens: from research to the clinic

Williamson

2019

Clinical and Experimental Immunology

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Summary In this two‐part series of reviews, we have invited experts in their fields to contribute articles on the status of vaccine research and development for emerging pathogens. This topic has been brought into sharp focus in recent years following significant outbreaks of viral diseases such as those causing severe acute respiratory syndrome and Middle East respiratory syndrome, as well as devastating outbreaks of diseases caused by the Ebola, Marburg, Zika and Lassa fever viruses, to name only a few examples. Additionally, bacterial infections leading to bubonic and pneumonic plague, most notably in Madagascar in 2018, as well as malaria in many tropical countries, melioidosis in south east Asia and tularaemia in northern Europe and North America, have incurred significant morbidity and mortality. In this review series, the life cycle of these pathogens and the epidemiology of disease have been reviewed in the context of potential points of intervention for the prevention of human infection. Many of the emerging pathogens are zoonoses and, as such, there is scope for intervention at the animal/insect/environmental reservoir. Other pathogens covered in this review series are considered to be re‐emerging, such as multi‐drug resistant tuberculosis.

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HLA-E: exploiting pathogen-host interactions for vaccine development

Cited by 33 publications

References 101 publications

The Cynomolgus Macaque MHC Polymorphism in Experimental Medicine

The Cynomolgus Macaque MHC Polymorphism in Experimental Medicine

Vaccine Vectors Harnessing the Power of Cytomegaloviruses

Vaccines for emerging pathogens: from research to the clinic

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