Vaccination against trypanosomiasis

Greca, Florencia La; Magez, Stefan

doi:10.4161/hv.7.11.18203

Cited by 63 publications

(24 citation statements)

References 86 publications

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“…Severe immunosuppression occurring in the mouse model [46] may have also biased against identifying antigenically distinct variants. On the other hand, incomplete variation through SGC might be sufficient in the context of a complex natural infection, where antibody clearance might operate [47], differentiation and incomplete cross-reaction suppress variants below the levels required to induce potent, specific responses [38], and host immunity is suppressed [48].…”

Section: Discussionmentioning

confidence: 99%

Mosaic VSGs and the Scale of Trypanosoma brucei Antigenic Variation

2013

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A main determinant of prolonged Trypanosoma brucei infection and transmission and success of the parasite is the interplay between host acquired immunity and antigenic variation of the parasite variant surface glycoprotein (VSG) coat. About 0.1% of trypanosome divisions produce a switch to a different VSG through differential expression of an archive of hundreds of silent VSG genes and pseudogenes, but the patterns and extent of the trypanosome diversity phenotype, particularly in chronic infection, are unclear. We applied longitudinal VSG cDNA sequencing to estimate variant richness and test whether pseudogenes contribute to antigenic variation. We show that individual growth peaks can contain at least 15 distinct variants, are estimated computationally to comprise many more, and that antigenically distinct ‘mosaic’ VSGs arise from segmental gene conversion between donor VSG genes or pseudogenes. The potential for trypanosome antigenic variation is probably much greater than VSG archive size; mosaic VSGs are core to antigenic variation and chronic infection.

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Section: Discussionmentioning

confidence: 99%

Mosaic VSGs and the Scale of Trypanosoma brucei Antigenic Variation

2013

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“…All of the important livestock trypanosomes described above are extracellular parasites in mammals and evade the host immune defences by continuously changing their surface coat (Horn, 2014), one of the immune-evading mechanisms that essentially preclude the development of conventional vaccines (La Greca and Magez, 2011; Cnops et al 2015). Hence, control of animal trypanosomiases relies primarily on the use of insecticides or traps to control the vector (especially in the case of tsetse-transmitted trypanosomiases), and on the use of trypanocides to control the parasite (Holmes, 2013).…”

Section: Control Strategies and Trypanotolerancementioning

confidence: 99%

The animal trypanosomiases and their chemotherapy: a review

et al. 2016

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SUMMARYPathogenic animal trypanosomes affecting livestock have represented a major constraint to agricultural development in Africa for centuries, and their negative economic impact is increasing in South America and Asia. Chemotherapy and chemoprophylaxis represent the main means of control. However, research into new trypanocides has remained inadequate for decades, leading to a situation where the few compounds available are losing efficacy due to the emergence of drug-resistant parasites. In this review, we provide a comprehensive overview of the current options available for the treatment and prophylaxis of the animal trypanosomiases, with a special focus on the problem of resistance. The key issues surrounding the main economically important animal trypanosome species and the diseases they cause are also presented. As new investment becomes available to develop improved tools to control the animal trypanosomiases, we stress that efforts should be directed towards a better understanding of the biology of the relevant parasite species and strains, to identify new drug targets and interrogate resistance mechanisms.

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“…In 2011, we published a comprehensive overview of antitrypanosome vaccine data that was available at the time (119). We concluded that while there is a fair amount of "promising" results in the literature, there is little prospect of seeing a successful field applicable vaccine any time soon.…”

Section: Experimental Anti-trypanosome Vaccines Have So Far Not Been mentioning

confidence: 99%

Infections With Extracellular Trypanosomes Require Control by Efficient Innate Immune Mechanisms and Can Result in the Destruction of the Mammalian Humoral Immune System

et al. 2020

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Salivarian trypanosomes are extracellular parasites that affect humans, livestock, and game animals around the world. Through co-evolution with the mammalian immune system, trypanosomes have developed defense mechanisms that allow them to thrive in blood, lymphoid vessels, and tissue environments such as the brain, the fat tissue, and testes. Trypanosomes have developed ways to circumvent antibody-mediated killing and block the activation of the lytic arm of the complement pathway. Hence, this makes the innate immune control of the infection a crucial part of the host-parasite interaction, determining infection susceptibility, and parasitemia control. Indeed, trypanosomes use a combination of several independent mechanisms to avoid clearance by the humoral immune system. First, perpetuated antigenic variation of the surface coat allows to escape antibody-mediated elimination. Secondly, when antibodies bind to the coat, they are efficiently transported toward the endocytosis pathway, where they are removed from the coat proteins. Finally, trypanosomes engage in the active destruction of the mammalian humoral immune response. This provides them with a rescue solution in case antigenic variation does not confer total immunological invisibility. Both antigenic variation and B cell destruction pose significant hurdles for the development of anti-trypanosome vaccine strategies. However, developing total immune escape capacity and unlimited growth capabilities within a mammalian host is not beneficial for any parasite, as it will result in the accelerated death of the host itself. Hence, trypanosomes have acquired a system of quorum sensing that results in density-dependent population growth arrest in order to prevent overpopulating the host. The same system could possibly sense the infection-associated host tissue damage resulting from inflammatory innate immune responses, in which case the quorum sensing serves to prevent excessive immunopathology and as such also promotes host survival. In order to put these concepts together, this review summarizes current knowledge on the interaction between Magez et al.Trypanosomosis and Innate Immune Control trypanosomes and the mammalian innate immune system, the mechanisms involved in population growth regulation, antigenic variation and the immuno-destructive effect of trypanosomes on the humoral immune system. Vaccine trials and a discussion on the role of innate immune modulation in these trials are discussed at the end.

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Vaccination against trypanosomiasis

Cited by 63 publications

References 86 publications

Mosaic VSGs and the Scale of Trypanosoma brucei Antigenic Variation

Mosaic VSGs and the Scale of Trypanosoma brucei Antigenic Variation

The animal trypanosomiases and their chemotherapy: a review

Infections With Extracellular Trypanosomes Require Control by Efficient Innate Immune Mechanisms and Can Result in the Destruction of the Mammalian Humoral Immune System

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