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Development of Paramyosin as a Vaccine Candidate for Schistosomiasis.

Jiz MA, Wu H, Olveda R, Jarilla B, Kurtis JD - Front Immunol (2015)

Bottom Line: Schistosomiasis, caused by three principal species of diecious trematodes (flatworms), currently afflicts over 250 million individuals, results in an estimated 2-15% chronic disability, and contributes to poor health and economic stagnation in endemic areas.Paramyosin (Pmy), an invertebrate muscle-associated protein, has emerged as a promising vaccine candidate for both Schistosoma mansoni and Schistosoma japonicum.Herein, we discuss the discovery of Pmy, its development as a vaccine candidate in rodents and bovines, as well as studies of naturally occurring immune responses to Pmy in prospective, observational human studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Health, Research Institute for Tropical Medicine , Manila , Philippines.

ABSTRACT
Schistosomiasis, caused by three principal species of diecious trematodes (flatworms), currently afflicts over 250 million individuals, results in an estimated 2-15% chronic disability, and contributes to poor health and economic stagnation in endemic areas. Although schistosomiasis is effectively treated with praziquantel, rapid reinfection with rebound morbidity precludes effective control based on chemotherapy alone and justifies current efforts to develop vaccines for these parasites. Paramyosin (Pmy), an invertebrate muscle-associated protein, has emerged as a promising vaccine candidate for both Schistosoma mansoni and Schistosoma japonicum. Herein, we discuss the discovery of Pmy, its development as a vaccine candidate in rodents and bovines, as well as studies of naturally occurring immune responses to Pmy in prospective, observational human studies. We conclude with a proposed developmental plan to move Pmy toward Phase I clinical trials.

No MeSH data available.


Related in: MedlinePlus

(A) Intensity of reinfection with S. japonicum 18 months after treatment with PZQ, as predicted by cytokine ratios in responses to SWAP (N = 493). White and black bars represent the back-transformed LS mean intensity of reinfection for the upper and lower quintile of IL13/IL12 log cytokine-ratio distribution. Error bars represent SEs. LS mean estimates, SEs, and p-values for difference in means between quintiles are adjusted for confounders and clustering. Adapted from Ref. (26). (B) IgE responses to rSj97 (paramyosin) predict resistance to S. japonicum reinfection at 12 months post-treatment, and are attenuated by lgG4. Least square (LS) means represent the mean reinfection egg burden after adjusting for potential confounders and clustering by household in a repeated measures model using the combined Sj97 IgE and lgG4 response variable (p = 0.023 for time by combined lgE–lgG4 variable interaction). Confounders in this model include age, gender, village of residence, exposure, and baseline intensity. p-values are for detailed comparisons between “lgG4 only” and the rest of the groups. Error bars represent SEs. Reprinted from Ref. (27).
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Figure 1: (A) Intensity of reinfection with S. japonicum 18 months after treatment with PZQ, as predicted by cytokine ratios in responses to SWAP (N = 493). White and black bars represent the back-transformed LS mean intensity of reinfection for the upper and lower quintile of IL13/IL12 log cytokine-ratio distribution. Error bars represent SEs. LS mean estimates, SEs, and p-values for difference in means between quintiles are adjusted for confounders and clustering. Adapted from Ref. (26). (B) IgE responses to rSj97 (paramyosin) predict resistance to S. japonicum reinfection at 12 months post-treatment, and are attenuated by lgG4. Least square (LS) means represent the mean reinfection egg burden after adjusting for potential confounders and clustering by household in a repeated measures model using the combined Sj97 IgE and lgG4 response variable (p = 0.023 for time by combined lgE–lgG4 variable interaction). Confounders in this model include age, gender, village of residence, exposure, and baseline intensity. p-values are for detailed comparisons between “lgG4 only” and the rest of the groups. Error bars represent SEs. Reprinted from Ref. (27).

Mentions: Schistosoma japonicum transmission was high: 54.8 and 91.1% were reinfected within 6 and 18 months, respectively. A Th2 bias in the following cytokine ratios, IL-5/IL-12, IL-13/IL-12, IL-4/IFN-g, IL-5/IFN-γ, and IL-13/IFN-γ, in response to Sj97, predicted a 30–41% lower intensity of reinfection (all p < 0.05) after adjustment for potential confounders. An example of one of these protective relationships (for IL-13/IFN-γ ratio) is presented in Figure 1A (27). Similar results were found for responses to SWAP.


Development of Paramyosin as a Vaccine Candidate for Schistosomiasis.

Jiz MA, Wu H, Olveda R, Jarilla B, Kurtis JD - Front Immunol (2015)

(A) Intensity of reinfection with S. japonicum 18 months after treatment with PZQ, as predicted by cytokine ratios in responses to SWAP (N = 493). White and black bars represent the back-transformed LS mean intensity of reinfection for the upper and lower quintile of IL13/IL12 log cytokine-ratio distribution. Error bars represent SEs. LS mean estimates, SEs, and p-values for difference in means between quintiles are adjusted for confounders and clustering. Adapted from Ref. (26). (B) IgE responses to rSj97 (paramyosin) predict resistance to S. japonicum reinfection at 12 months post-treatment, and are attenuated by lgG4. Least square (LS) means represent the mean reinfection egg burden after adjusting for potential confounders and clustering by household in a repeated measures model using the combined Sj97 IgE and lgG4 response variable (p = 0.023 for time by combined lgE–lgG4 variable interaction). Confounders in this model include age, gender, village of residence, exposure, and baseline intensity. p-values are for detailed comparisons between “lgG4 only” and the rest of the groups. Error bars represent SEs. Reprinted from Ref. (27).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4508564&req=5

Figure 1: (A) Intensity of reinfection with S. japonicum 18 months after treatment with PZQ, as predicted by cytokine ratios in responses to SWAP (N = 493). White and black bars represent the back-transformed LS mean intensity of reinfection for the upper and lower quintile of IL13/IL12 log cytokine-ratio distribution. Error bars represent SEs. LS mean estimates, SEs, and p-values for difference in means between quintiles are adjusted for confounders and clustering. Adapted from Ref. (26). (B) IgE responses to rSj97 (paramyosin) predict resistance to S. japonicum reinfection at 12 months post-treatment, and are attenuated by lgG4. Least square (LS) means represent the mean reinfection egg burden after adjusting for potential confounders and clustering by household in a repeated measures model using the combined Sj97 IgE and lgG4 response variable (p = 0.023 for time by combined lgE–lgG4 variable interaction). Confounders in this model include age, gender, village of residence, exposure, and baseline intensity. p-values are for detailed comparisons between “lgG4 only” and the rest of the groups. Error bars represent SEs. Reprinted from Ref. (27).
Mentions: Schistosoma japonicum transmission was high: 54.8 and 91.1% were reinfected within 6 and 18 months, respectively. A Th2 bias in the following cytokine ratios, IL-5/IL-12, IL-13/IL-12, IL-4/IFN-g, IL-5/IFN-γ, and IL-13/IFN-γ, in response to Sj97, predicted a 30–41% lower intensity of reinfection (all p < 0.05) after adjustment for potential confounders. An example of one of these protective relationships (for IL-13/IFN-γ ratio) is presented in Figure 1A (27). Similar results were found for responses to SWAP.

Bottom Line: Schistosomiasis, caused by three principal species of diecious trematodes (flatworms), currently afflicts over 250 million individuals, results in an estimated 2-15% chronic disability, and contributes to poor health and economic stagnation in endemic areas.Paramyosin (Pmy), an invertebrate muscle-associated protein, has emerged as a promising vaccine candidate for both Schistosoma mansoni and Schistosoma japonicum.Herein, we discuss the discovery of Pmy, its development as a vaccine candidate in rodents and bovines, as well as studies of naturally occurring immune responses to Pmy in prospective, observational human studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Health, Research Institute for Tropical Medicine , Manila , Philippines.

ABSTRACT
Schistosomiasis, caused by three principal species of diecious trematodes (flatworms), currently afflicts over 250 million individuals, results in an estimated 2-15% chronic disability, and contributes to poor health and economic stagnation in endemic areas. Although schistosomiasis is effectively treated with praziquantel, rapid reinfection with rebound morbidity precludes effective control based on chemotherapy alone and justifies current efforts to develop vaccines for these parasites. Paramyosin (Pmy), an invertebrate muscle-associated protein, has emerged as a promising vaccine candidate for both Schistosoma mansoni and Schistosoma japonicum. Herein, we discuss the discovery of Pmy, its development as a vaccine candidate in rodents and bovines, as well as studies of naturally occurring immune responses to Pmy in prospective, observational human studies. We conclude with a proposed developmental plan to move Pmy toward Phase I clinical trials.

No MeSH data available.


Related in: MedlinePlus