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Schistosome Vaccine Adjuvants in Preclinical and Clinical Research.

Stephenson R, You H, McManus DP, Toth I - Vaccines (Basel) (2014)

Bottom Line: Despite many researchers working towards this goal, one of the focuses has been on identifying new antigenic targets.Adjuvant selection has a large impact on the effectiveness of the vaccine, and the use of adjuvants to aid in the stimulation of the immune system is a critical step and a major variable affecting vaccine development.In addition to a comprehensive understanding of the immune system, level of protection and the desired immune response required, there is also a need for a standardised and effective adjuvant formulation.

View Article: PubMed Central - PubMed

Affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia. r.stephenson@uq.edu.au.

ABSTRACT
There is currently no vaccine available for human use for any parasitic infections, including the helminth disease, schistosomiasis. Despite many researchers working towards this goal, one of the focuses has been on identifying new antigenic targets. The bar to achieve protective efficacy in humans was set at a consistent induction of 40% protection or better by the World Health Organisation (WHO), and although this is a modest goal, it is yet to be reached with the six most promising schistosomiasis vaccine candidates (Sm28GST, IrV5, Sm14, paramyosin, TPI, and Sm23). Adjuvant selection has a large impact on the effectiveness of the vaccine, and the use of adjuvants to aid in the stimulation of the immune system is a critical step and a major variable affecting vaccine development. In addition to a comprehensive understanding of the immune system, level of protection and the desired immune response required, there is also a need for a standardised and effective adjuvant formulation. This review summarises the status of adjuvants that have been or are being employed in schistosomiasis vaccine development focusing on immunisation outcomes at preclinical and clinical stages.

No MeSH data available.


Related in: MedlinePlus

A model demonstrating the balance between Th1 (cell-mediated) and Th2 (humoral) response of the adaptive (specific) immune system; a balance is essential to prevent disease. Both Th1 and Th2 responses are tightly controlled but excessive activation may cause or alter the disease state. Cytokines are most commonly grouped by their functional similarities and one of the most prominent concepts used to discriminate two distinct ways that the specific immune system can react on environmental stimuli is the classification of Th1 and Th2 cell diversity. This classification is based on the cytokine production patterns of T helper cells and reflects the polarization of the immune system to either a cell-mediated (Thl) or a humoral (Th2) immune response [8].
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vaccines-02-00654-f001: A model demonstrating the balance between Th1 (cell-mediated) and Th2 (humoral) response of the adaptive (specific) immune system; a balance is essential to prevent disease. Both Th1 and Th2 responses are tightly controlled but excessive activation may cause or alter the disease state. Cytokines are most commonly grouped by their functional similarities and one of the most prominent concepts used to discriminate two distinct ways that the specific immune system can react on environmental stimuli is the classification of Th1 and Th2 cell diversity. This classification is based on the cytokine production patterns of T helper cells and reflects the polarization of the immune system to either a cell-mediated (Thl) or a humoral (Th2) immune response [8].

Mentions: Schistosomes appear to have evolved a number of strategies to down-regulate the host’s immune response to promote their own survival [7]. T cell mediated immunity has been shown to be essential in the fight against schistosomiasis (reviewed by [3,4,7,8] and references within). Schistosomes, like other parasitic helminths, induce prominent T helper type 2 (Th2, humoral) responses with a quantifiable shift from gamma interferon (IFN-γ) and T helper type 1 (Th1, cellular) responses to an elevated production of interleukin (IL)-4 and Th2 in the spleens of infected mice [4,9]. However, disease severity and the immune response is complicated by the host’s genetics, the intensity of the infection, co-infection status, and in-utero sensitisation to schistosome antigens (compared to a naïve individual) [4]. Furthermore, humans who are infected with schistosomes, in general, have a Th2 type response, but, on the basis of IFN-γ and IL-5 levels, a Th1-like immune response is generated for some individuals [4]. IL-10 has also been shown to play an important role in schistosomiasis by preventing the development of Th1 and Th2-mediated pathologies [4]. Overall, a balance between Th1 and Th2 is required and a skewed response too heavily in either direction has harmful consequences for the host. Indeed, the vast majority of people living with schistosome infections elicit a balanced immune response that holds both the pathology and parasite in harmony (Figure 1) [8].


Schistosome Vaccine Adjuvants in Preclinical and Clinical Research.

Stephenson R, You H, McManus DP, Toth I - Vaccines (Basel) (2014)

A model demonstrating the balance between Th1 (cell-mediated) and Th2 (humoral) response of the adaptive (specific) immune system; a balance is essential to prevent disease. Both Th1 and Th2 responses are tightly controlled but excessive activation may cause or alter the disease state. Cytokines are most commonly grouped by their functional similarities and one of the most prominent concepts used to discriminate two distinct ways that the specific immune system can react on environmental stimuli is the classification of Th1 and Th2 cell diversity. This classification is based on the cytokine production patterns of T helper cells and reflects the polarization of the immune system to either a cell-mediated (Thl) or a humoral (Th2) immune response [8].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494218&req=5

vaccines-02-00654-f001: A model demonstrating the balance between Th1 (cell-mediated) and Th2 (humoral) response of the adaptive (specific) immune system; a balance is essential to prevent disease. Both Th1 and Th2 responses are tightly controlled but excessive activation may cause or alter the disease state. Cytokines are most commonly grouped by their functional similarities and one of the most prominent concepts used to discriminate two distinct ways that the specific immune system can react on environmental stimuli is the classification of Th1 and Th2 cell diversity. This classification is based on the cytokine production patterns of T helper cells and reflects the polarization of the immune system to either a cell-mediated (Thl) or a humoral (Th2) immune response [8].
Mentions: Schistosomes appear to have evolved a number of strategies to down-regulate the host’s immune response to promote their own survival [7]. T cell mediated immunity has been shown to be essential in the fight against schistosomiasis (reviewed by [3,4,7,8] and references within). Schistosomes, like other parasitic helminths, induce prominent T helper type 2 (Th2, humoral) responses with a quantifiable shift from gamma interferon (IFN-γ) and T helper type 1 (Th1, cellular) responses to an elevated production of interleukin (IL)-4 and Th2 in the spleens of infected mice [4,9]. However, disease severity and the immune response is complicated by the host’s genetics, the intensity of the infection, co-infection status, and in-utero sensitisation to schistosome antigens (compared to a naïve individual) [4]. Furthermore, humans who are infected with schistosomes, in general, have a Th2 type response, but, on the basis of IFN-γ and IL-5 levels, a Th1-like immune response is generated for some individuals [4]. IL-10 has also been shown to play an important role in schistosomiasis by preventing the development of Th1 and Th2-mediated pathologies [4]. Overall, a balance between Th1 and Th2 is required and a skewed response too heavily in either direction has harmful consequences for the host. Indeed, the vast majority of people living with schistosome infections elicit a balanced immune response that holds both the pathology and parasite in harmony (Figure 1) [8].

Bottom Line: Despite many researchers working towards this goal, one of the focuses has been on identifying new antigenic targets.Adjuvant selection has a large impact on the effectiveness of the vaccine, and the use of adjuvants to aid in the stimulation of the immune system is a critical step and a major variable affecting vaccine development.In addition to a comprehensive understanding of the immune system, level of protection and the desired immune response required, there is also a need for a standardised and effective adjuvant formulation.

View Article: PubMed Central - PubMed

Affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia. r.stephenson@uq.edu.au.

ABSTRACT
There is currently no vaccine available for human use for any parasitic infections, including the helminth disease, schistosomiasis. Despite many researchers working towards this goal, one of the focuses has been on identifying new antigenic targets. The bar to achieve protective efficacy in humans was set at a consistent induction of 40% protection or better by the World Health Organisation (WHO), and although this is a modest goal, it is yet to be reached with the six most promising schistosomiasis vaccine candidates (Sm28GST, IrV5, Sm14, paramyosin, TPI, and Sm23). Adjuvant selection has a large impact on the effectiveness of the vaccine, and the use of adjuvants to aid in the stimulation of the immune system is a critical step and a major variable affecting vaccine development. In addition to a comprehensive understanding of the immune system, level of protection and the desired immune response required, there is also a need for a standardised and effective adjuvant formulation. This review summarises the status of adjuvants that have been or are being employed in schistosomiasis vaccine development focusing on immunisation outcomes at preclinical and clinical stages.

No MeSH data available.


Related in: MedlinePlus