Differential T-cell responses of semi-immune and susceptible malaria subjects to in silico predicted and synthetic peptides of Plasmodium falciparum

Dinga, Jerome Nyhalah; Mbandi, Stanley Kimbung; Cho-Ngwa, Fidelis; Fon, Nde Peter; Moliki, Johnson Mosoko; Efeti, Rose Mary; Nyasa, Babila Raymond; Anong, Damian Nota; Jojić, Nebojša; Heckerman, David; Wang, Ruobing; Titanji, Vincent P. K.

doi:10.1016/j.actatropica.2014.03.007

Cited by 8 publications

(13 citation statements)

References 25 publications

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“…The present investigation demonstrates that T‐cell response to UB09, the other component of the dimeric chimera displays similar properties as UB05, suggesting that it too is a potential marker of protective immunity to malaria. It should be noted that a recent survey suggested that most P. falciparum antigens evoked strong T‐cell responses in both semi‐immune and susceptible subjects , a situation which compounded the dissection of the responses. By using protein fragments rather than whole antigens we have succeeded to obtain a reagent that evokes strong T‐cell responses in one group (SIS) but not the other (FSS).…”

Section: Discussionmentioning

confidence: 67%

“…Sixty three participants were admitted into the study from amongst residents of Molyko and Bolifamba quarters of Buea. Buea is a multi‐ethnic town with endemic malaria along the flanks of Mount Cameroon in the South West region of the Republic of Cameroon .…”

Section: Methodsmentioning

confidence: 99%

“…The antigens were used at 5 μg/mL, with 300 000 PBMCs and each antigen was tested in triplicates. The ELISpot assay was carried out using MABTECH AB kits as previously described . The anti‐CD3‐2 monoclonal antibody was used as a positive control to recall T cell memory.…”

Section: Methodsmentioning

confidence: 99%

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Differential T‐cell responses to a chimeric Plasmodium falciparum antigen; UB05‐09, correlates with acquired immunity to malaria

Dinga

Njimoh

Kiawa

et al. 2016

Parasite Immunology

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The development of a sterilizing and cost-effective vaccine against malaria remains a major problem despite recent advances. In this study, it is demonstrated that two antigens of P. falciparum UB05, UB09 and their chimera UB05-09 can serve as protective immunity markers by eliciting higher T-cell responses in malaria semi-immune subjects (SIS) than in frequently sick subjects (FSS) and could be used to distinguish these two groups. UB05, UB09 and UB05-09 were cloned, expressed in E. coli, purified and used to stimulate PBMCs isolated from 63 subjects in a malaria endemic area, for IFN-γ production, which was measured by the ELISpot assay. The polymorphism of UB09 gene in the malaria infected population was also studied by PCR/sequencing of the gene in P. falciparum field isolates. All three antigens were preferentially recognized by PBMCs from SIS. IFN-γ production induced by these antigens correlated with the absence of fever and parasitaemia. UB09 was shown to be relatively well-conserved in nature. It is concluded that UB05, UB09 and the chimera UB05-09 posses T-cell epitopes that are associated with protection against malaria and could thus be used to distinguish SIS from FSS eventhough acute infection with malaria has been shown to reduce cytokine production in some studies. Further investigations of these antigens as potential diagnostic and/or vaccine candidates for malaria are indicated.

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Section: Discussionmentioning

confidence: 67%

Section: Methodsmentioning

confidence: 99%

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Differential T‐cell responses to a chimeric Plasmodium falciparum antigen; UB05‐09, correlates with acquired immunity to malaria

Dinga

Njimoh

Kiawa

et al. 2016

Parasite Immunology

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“…Even though a number of blood‐stage antigens are under vaccine development, it is still possible and necessary to search for more subunit vaccine candidates to improve the outcome of vaccination. While reverse vaccinology and the use of orthologous proteins are methods that have been used to identify antigens that are involved in host‐parasite interactions, it would be more desirable to use unbiased methods to identify antigens that are implicated in immune protection.…”

Section: Introductionmentioning

confidence: 99%

Preclinical efficacy and immunogenicity assessment to show that a chimeric Plasmodium falciparum UB05‐09 antigen could be a malaria vaccine candidate

Dinga

Gamua

Ghogomu

et al. 2018

Parasite Immunology

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SummaryAlthough it is generally agreed that an effective vaccine would greatly accelerate the control of malaria, the lone registered malaria vaccine Mosquirix™ has an efficacy of 30%‐60% that wanes rapidly, indicating a need for improved second‐generation malaria vaccines. Previous studies suggested that immune responses to a chimeric Plasmodium falciparum antigen UB05‐09 are associated with immune protection against malaria. Herein, the preclinical efficacy and immunogenicity of UB05‐09 are tested. Growth inhibition assay was employed to measure the effect of anti‐UB05‐09 antibodies on P. falciparum growth in vitro. BALB/c mice were immunized with UB05‐09 and challenged with the lethal Plasmodium yoelii 17XL infection. ELISA was used to measure antigen‐specific antibody production. ELISPOT assays were employed to measure interferon‐gamma production ex vivo after stimulation with chimeric UB05‐09 and its constituent antigens. Purified immunoglobulins raised in rabbits against UB05‐09 significantly inhibited P. falciparum growth in vitro compared to that of its respective constituent antigens. A combination of antibodies to UB05‐09 and the apical membrane antigen (AMA1) completely inhibited P. falciparum growth in culture. Immunization of BALB/c mice with recombinant UB05‐09 blocked parasitaemia and protected them against lethal P. yoelii 17XL challenge infection. These data suggest that UB05‐09 is a malaria vaccine candidate that could be developed further and used in conjunction with AMA1 to create a potent malaria vaccine.

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“…The proposal has been the "alliance" between biology, medicine and computer science, which allows the development of experiments in silico, which is promising on malaria research (DINGA et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Plasmodium Falciparum Infection: In Silico Preliminary Studies

Gomes

Moreira

Dias

et al. 2016

Abakos

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Plasmodium falciparum INFECTION ResumoA malária é uma doença infecciosa de grande impacto em termos de saúde pública -dado o contingente de pessoas afetadas e submetidas ao risco de adoecer -, causada por protozoá-rios do gênero Plasmodium. São conhecidas cinco principais espécies capazes de infectar humanos: Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae e Plasmodium knowlesi, destacando-se a primeira como aquela capaz de produzir os quadros de maior gravidade. A despeito de sua relevância clínica e epidemiológica e das investigações em desenvolvimento -dirigidas aos diferentes aspectos da interação entre o homem e os protozoários do gênero Plasmodium -permanecem inúmeras dúvidas sobre distintos aspectos do processo fisiopatológico da malária. Para estudar tais lacunas, pode-se buscar estratégias interdisciplinares envolvendo biologia, medicina e ciência da computação, no âmbito da experimentação in silico. Tal abordagem apresenta rapidez, baixo custo e a não implicação em questões éticas que permeiam as experimentações in vitro e in vivo.Com base nessas considerações, o presente artigo apresenta os resultados preliminares de um modelo computacional de interação entre P. falciparum e eritrócitos, os quais foram implementados -computacionalmente -no sistema AutoSimmune. Os resultados obtidos demonstram que o sistema é capaz de simular o processo de infecção das células hospedeiras pelo protozoário, apresentando, assim, similaridade com a realidade biológica. AbstractMalaria is an infectious disease of great impact in terms of public health, given the number of people affected and subjected to the risk of illness. Protozoa of the genus Plasmodium cause it and five species can infect humans: Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae and Plasmodium knowlesi; the first is able to produce the most severe cases of the disease. Despite its clinical and epidemiological relevance and investigations in development -targeted at different aspects of the interaction between humans and Plasmodium protozoa of the genus -there remains many questions about different aspects of the malaria pathophysiology. To study such gaps, interdisciplinary strategies can be pursed, which involve biology, medicine an computer science, as part of the trial in silico. Such approach provides agility, low cost and does not imply ethical issues that permeate the experiments in vitro and in vivo. Based on these considerations, this article presents preliminary results of a computational model of the interaction between P. falciparum and erythrocytes, implemented in AutoSimmune system. The results obtained show that the system is able to simulate the host cells infection process by protozoan with similarities with the biological reality.

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Differential T-cell responses of semi-immune and susceptible malaria subjects to in silico predicted and synthetic peptides of Plasmodium falciparum

Cited by 8 publications

References 25 publications

Differential T‐cell responses to a chimeric Plasmodium falciparum antigen; UB05‐09, correlates with acquired immunity to malaria

Differential T‐cell responses to a chimeric Plasmodium falciparum antigen; UB05‐09, correlates with acquired immunity to malaria

Preclinical efficacy and immunogenicity assessment to show that a chimeric Plasmodium falciparum UB05‐09 antigen could be a malaria vaccine candidate

Plasmodium Falciparum Infection: In Silico Preliminary Studies

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