The Search for a Schistosomiasis Vaccine: Australia's Contribution.
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ABSTRACT:
SUBMITTER: McManus DP
PROVIDER: S-EPMC8402410 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Schistosomiasis is a parasitic disease caused by helminths belonging to the Schistosoma genus. Approximately 700 million people are at risk of infection and 200 million people are currently infected. Schistosomiasis is the most important helminth infection, and treatment relies solely on the drug praziquantel. Worries of praziquantel resistance as well as high disease burden are only some of the justifications which support the development of a vaccine against schistosomiasis. To date, only 2 schistosome vaccines have made it into clinical trials: Sh28GST (Bilhvax) and Sm14. However, there are several vaccine candidates, such as TSP-2, sm-p8, and Sm-Cathepsin B, which are generating promising results in pre-clinical studies. Schistosomiasis vaccine development has been an uphill battle, and there are still several hurdles to overcome in the future. Fortunately, the research groups involved in the research for vaccine development have not abandoned their work. Furthermore, in the last few years, schistosomiasis has garnered some additional attention on a global scale due to its significant impact on public health.
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Project description:Schistosomiasis is a neglected tropical disease (NTD) of public health importance. Despite decades of implementation of mass praziquantel therapy programs and other control measures, schistosomiasis has not been contained and continues to spread to new geographic areas. A schistosomiasis vaccine could play an important role as part of a multifaceted control approach. With regards to vaccine development, many biological bottlenecks still exist: the lack of reliable surrogates of protection in humans; immune interactions in co-infections with other diseases in endemic areas; the potential risk of IgE responses to antigens in endemic populations; and paucity of appropriate vaccine efficacy studies in nonhuman primate models. Research is also needed on the role of modern adjuvants targeting specific parts of the innate immune system to tailor a potent and protective immune response for lead schistosome vaccine candidates with the long-term aim to achieve curative worm reduction. This review summarizes the current status of schistosomiasis vaccine development.
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Project description:The global carbon cycle is highly sensitive to climate-driven fluctuations of precipitation, especially in the Southern Hemisphere. This was clearly manifested by a 20% increase of the global terrestrial C sink in 2011 during the strongest sustained La Niña since 1917. However, inconsistencies exist between El Niño/La Niña (ENSO) cycles and precipitation in the historical record; for example, significant ENSO-precipitation correlations were present in only 31% of the last 100 years, and often absent in wet years. To resolve these inconsistencies, we used an advanced temporal scaling method for identifying interactions amongst three key climate modes (El Niño, the Indian Ocean dipole, and the southern annular mode). When these climate modes synchronised (1999-2012), drought and extreme precipitation were observed across Australia. The interaction amongst these climate modes, more than the effect of any single mode, was associated with large fluctuations in precipitation and productivity. The long-term exposure of vegetation to this arid environment has favoured a resilient flora capable of large fluctuations in photosynthetic productivity and explains why Australia was a major contributor not only to the 2011 global C sink anomaly but also to global reductions in photosynthetic C uptake during the previous decade of drought.
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Project description:Schistosomiasis causes significant levels of morbidity and mortality in many geographical regions of the world. The disease is caused by infections with parasitic blood flukes known as schistosomes. The control of schistosomiasis over the last several decades has been centered on the mass drug administration (MDA) of praziquantel (PZQ), which is the only drug currently available for treatment. Despite the concerted efforts of MDA programs, the prevalence and transmission of schistosomiasis has remained largely unchecked due to the fact that PZQ is ineffective against juvenile schistosomes, does not prevent re-infection and the emergence of PZQ-resistant parasites. In addition, other measures such as the water, sanitation and hygiene programs and snail intermediate hosts control have had little to no impact. These drawbacks indicate that the current control strategies are severely inadequate at interrupting transmission and therefore, implementation of other control strategies are required. Ideally, an efficient vaccine is what is needed for long term protection thereby eliminating the current efforts of repeated mass drug administration. However, the general consensus in the field is that the integration of a viable vaccine with MDA and other control measures offer the best chance of achieving the goal of schistosomiasis elimination. This review focuses on the present status of schistosomiasis vaccine candidates in different phases of human clinical trials and provide some insight into future vaccine discovery and design.
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Project description:A digenetic platyhelminth Schistosoma is the causative agent of schistosomiasis, one of the neglected tropical diseases that affect humans and animals in numerous countries in the Middle East, sub-Saharan Africa, South America and China. Several control methods were used for prevention of infection or treatment of acute and chronic disease. Mass drug administration led to reduction in heavy-intensity infections and morbidity, but failed to decrease schistosomiasis prevalence and eliminate transmission, indicating the need to develop anti-schistosome vaccine to prevent infection and parasite transmission. This review summarizes the efficacy and protective capacity of available schistosomiasis vaccine candidates with some insights and future prospects.
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Project description:Schistosomiasis is a neglected tropical disease of humans, and it is considered to be the second most devastating parasitic disease after malaria. Eggs produced by normally developed female worms are important in the transmission of the parasite, and they responsible for the pathogenesis of schistosomiasis. The tumor suppressor gene lethal giant larvae (lgl) has an essential function in establishing apical-basal cell polarity, cell proliferation, differentiation, and tissue organization. In our earlier study, downregulation of the lgl gene induced a significant reduction in the egg hatching rate of Schistosoma japonicum (Sj) eggs. In this study, the Sjlgl gene was used as a vaccine candidate against schistosomiasis, and vaccination achieved and maintained a stable reduction of the egg hatching rate, which is consistent with previous studies, in addition to reducing the worm burden and liver egg burden in some trials.
| S-EPMC5120214 | biostudies-literature
Project description:Comparison of mitochondrial DNA variation among populations of three endemic lizard species in Australia's Wet Tropics rainforest reveals clear evidence of population-level response to Pleistocene rainforest contraction and subsequent expansion. This pattern is repeated in two separate rainforest regions (natural replicates), between which populations have been separated for several million years. Despite evidence for isolation in rainforest refugia, historically reduced effective population size, and recent range expansion, little or no detectable phenotypic evolution has occurred among populations, even those isolated for several million years. These observations suggest that long-term isolation per se, even when combined with major reductions in population size and opportunities for drift and founder effects, is unlikely to be the primary process driving phenotypic divergence and speciation of rainforest vertebrates.
| S-EPMC1689665 | biostudies-other
Project description:Schistosomiasis remains a leading cause of chronic morbidity in endemic regions despite decades of widespread mass chemotherapy with praziquantel. Using our whole proteome differential screening approach, and plasma and epidemiologic data from a longitudinal cohort of individuals living in a Schistosoma japonicum-endemic region of the Philippines, we interrogated the parasite proteome to identify novel vaccine candidates for Schistosoma japonicum. We identified 16 parasite genes which encoded proteins that were recognized by immunoglobulin G or immunoglobulin E antibodies in the plasma of individuals who had developed resistance to reinfection, but were not recognized by antibodies in the plasma of individuals who remained susceptible to reinfection. Antibody levels to Sj6-8 and Sj4-1 measured in the entire cohort (N = 505) 1 month after praziquantel treatment were associated with significantly decreased risk of reinfection and lower intensity of reinfection over 18 months of follow-up.
| S-EPMC8030711 | biostudies-literature
Project description:ObjectivesTo examine the reported incidence and features of disseminated varicella zoster virus (VZV) infection following live attenuated herpes zoster vaccine live (ZVL: Zostavax, Merck) in immunocompromised people in Australia.Design and settingZVL was funded in 2016 in Australia for people aged 70 years, with a catch-up programme for those 71-79 years. From 2016 to 2020, three deaths due to disseminated vaccine-strain VZV infection occurred following inadvertent ZVL administration in individuals with varying levels of immunocompromise. This descriptive study examined 4 years of national surveillance data reported to the Therapeutic Goods Administration's Adverse Event Monitoring System (AEMS). Denominator data for rates were from doses recorded in the Australian Immunisation Register.ParticipantsIndividuals vaccinated between 1 November 2016 and 31 December 2020 who experienced adverse event(s) following immunisation (AEFI) after ZVL recorded in the AEMS.Primary and secondary outcome measuresRates and outcomes of confirmed (Oka strain positive) or probable disseminated VZV infection, and inadvertent administration of ZVL in immunocompromised individuals.Results854 AEFI were reported from 1 089 966 doses of ZVL administered (78.4 per 100 000 doses). Of those, 14 were classified as confirmed (n=6, 0.55 per 100 000) or probable (n=8) disseminated VZV infection. The confirmed cases were all hospitalised, and most (5/6) were immunocompromised; three cases died. Thirty-seven individuals were reported as vaccinated despite a contraindication due to immunocompromise (3.4 per 100 000), with 12/37 (32%) hospitalised.ConclusionsDisseminated VZV is potentially life-threatening and occurs mostly in those with severe immunocompromise. Inadvertent administration of ZVL to immunocompromised individuals has occurred despite initial provider guidance and education. Multiple additional strategies to assist providers to identify contraindications have been implemented to prevent adverse outcomes.
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Project description:Schistosomiasis is a neglected tropical disease inflicting significant morbidity in humans worldwide. The disease is caused by infections with a parasitic trematode belonging to the genus Schistosoma. Over 250 million people are currently infected globally, with an estimated disability-adjusted life-years of 1.9 million attributed to the disease. Current understanding, based on several immunological studies using experimental and human models of schistosomiasis, reveals that complex immune mechanisms play off each other in the acquisition of immune resistance to infection/reinfection. Nevertheless, the precise characteristics of these responses, the specific antigens against which they are elicited, and how these responses are intricately regulated are still being investigated. What is apparent is that immunity to schistosome infections develops slowly and over a prolonged period of time, augmented by the death of adult worms occurring naturally or by praziquantel therapy. In this review, aspects of immunity to schistosomiasis, host-parasite interactions and their impact on schistosomiasis vaccine development are discussed.
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