This review aims to summarize the currently viable vaccine strategies including the approved vaccines and the those in trials for next-generation malaria vaccines.Data on malaria vaccine development was collected thro...This review aims to summarize the currently viable vaccine strategies including the approved vaccines and the those in trials for next-generation malaria vaccines.Data on malaria vaccine development was collected through a comprehensive review.The literature search was performed using databases including Google Scholar,PubMed,NIH,and Web of Science.Various novel approaches of vaccination are being developed,including those based on radiation-attenuated strategies,monoclonal antibodies,targeted immunogenic peptides,RNA and DNA vaccines,nanoparticle-based vaccines,protein-based vaccination protocols,and whole organism-based vaccination strategies.Trials on RTS,S have entered phase Ⅲtesting,and those based on blood-stage vaccines and vaccines to interrupt malarial transmission have advanced to higher stages of trials.Mathematical modeling,combined drug and vaccine strategies,mass drug administration,polyvalent vaccine formulations,and targeted vaccination campaigns is playing an important role in malarial prevention.Furthermore,assessing coverage,accessibility,acceptability,deployment,compilation,and adherence to specific vaccination strategies in endemic regions is essential for vaccination drives against malaria.展开更多
Incorporation of biomolecular epitopes to malarial antigens should be explored in the development of straintranscending malarial vaccines.The present study sought to determine safety,immunogenicity and cross-species e...Incorporation of biomolecular epitopes to malarial antigens should be explored in the development of straintranscending malarial vaccines.The present study sought to determine safety,immunogenicity and cross-species efficacy of Plasmodium falciparum serine repeat antigen 5 polypeptide co-expressed with epitopes of BacilleCalmette Guerin(BCG),tetanus toxoid(TT) and a chemokine gene.Olive baboons and BALB/c mice were randomly assigned into vaccine and control groups.The vaccine group animals were primed and boosted twice with pIRES plasmids encoding the SERA5 + BCG + TT alone,or with either CCL5 or CCL20 and the control group with pIRES plasmid vector backbone.Mice and baboons were challenged with P.berghei ANKA and P.knowlesi H strain parasites,respectively.Safety was determined by observing for injection sites reactogenicities,hematology and clinical chemistry.Parasitaemia and survivorship profiles were used to determine cross-species efficacy,and T cell phenotypes,Th1-,Th2-type,T-regulatory immune responses and antibody responses were assessed to determine vaccine immunogenicity.The pSeBCGTT plasmid DNA vaccines were safe and induced Thl-,Th2-type,and Tregulatory responses vaccinated animals showed enhanced CD4~+(P〈0.01),CD 8~+ T cells(P〈 0.001) activation and IgG anti-SE36 antibodies responses(P〈 0.001) at week 4 and 8 post vaccination compared to the control group.Vaccinated mice had a 31.45-68.69%cumulative parasite load reduction and 60%suppression in baboons(P〈0.05)and enhanced survivorship(P〈 0.001) with no clinical signs of malaria compared to the control group.The results showed that the vaccines were safe,immunogenic and conferred partial cross-species protection.展开更多
This paper presents an in-host malaria model subject to anti-malarial drug treatment and malaria vaccine antigens combinations.Pontryagin's Maximum Principle is applied to establish optimal control strategies agai...This paper presents an in-host malaria model subject to anti-malarial drug treatment and malaria vaccine antigens combinations.Pontryagin's Maximum Principle is applied to establish optimal control strategies against infected erythrocytes,infected hepatocytes and malaria parasites.Results from numerical simulation reveal that a combination of preerythrocytic vaccine antigen,blood schizontocide and gametocytocide drugs would offer the best strategy to eradicate clinical P.falciparum malaria.Sensitivity analysis,further reveal that the efficacy of blood schizontocides and blood stage vaccines are crucial in the control of clinical malaria infection.Futhermore,we found that an effective blood schizontocide should be used alongside efficacious blood stage vaccine for rapid eradication of infective malaria parasites.The authors hope that the results of this study will help accelerate malaria elimination efforts by combining malaria vaccines and anti-malarial drugs against the deadly P.falciparum malaria.展开更多
Objective Four B and Th cell epitopes were selected from conservative domain of Plasmodium falciparum antigens to construct two groups of chimeric malaria DNA vaccines with different configurations and their antigeni...Objective Four B and Th cell epitopes were selected from conservative domain of Plasmodium falciparum antigens to construct two groups of chimeric malaria DNA vaccines with different configurations and their antigenicities were studied Methods The partially synthesized oligonucleotide was annealed, PCR amplified and cloned into a mammalian cell expression vector By using a pair of isocaudamers on the vector, different single copies of B epitopes were multiplied and were tenderly stringed into two groups of chimeric DNA vaccine with different configurations BALB/c mice were immunized with these DNA plasmids by either intramuscular or intradermal injections Results The antisera from the immunized mice tested by ELISA showed that only the configuration which had a single copy of universal T helper cell epitope, CS T3, located at the C terminal of the multi copy B cell epitopes induced a high antibody response The T helper cell epitope at any other position of the peptide, or the double T helper cell epitopes configured with the B cell epitopes did not enhance antibody response, and some configurations even decreased the humoral response to a B cell epitope Conclusion This study demonstrated that both combination and configuration of the epitope may affect the antigenicity of a chimeric multiple antigen展开更多
文摘This review aims to summarize the currently viable vaccine strategies including the approved vaccines and the those in trials for next-generation malaria vaccines.Data on malaria vaccine development was collected through a comprehensive review.The literature search was performed using databases including Google Scholar,PubMed,NIH,and Web of Science.Various novel approaches of vaccination are being developed,including those based on radiation-attenuated strategies,monoclonal antibodies,targeted immunogenic peptides,RNA and DNA vaccines,nanoparticle-based vaccines,protein-based vaccination protocols,and whole organism-based vaccination strategies.Trials on RTS,S have entered phase Ⅲtesting,and those based on blood-stage vaccines and vaccines to interrupt malarial transmission have advanced to higher stages of trials.Mathematical modeling,combined drug and vaccine strategies,mass drug administration,polyvalent vaccine formulations,and targeted vaccination campaigns is playing an important role in malarial prevention.Furthermore,assessing coverage,accessibility,acceptability,deployment,compilation,and adherence to specific vaccination strategies in endemic regions is essential for vaccination drives against malaria.
基金Gene Art for engineering the vaccine constructs and the Uganda Council of Science and Technology (UCST)/World Bank for providing the funds for the work
文摘Incorporation of biomolecular epitopes to malarial antigens should be explored in the development of straintranscending malarial vaccines.The present study sought to determine safety,immunogenicity and cross-species efficacy of Plasmodium falciparum serine repeat antigen 5 polypeptide co-expressed with epitopes of BacilleCalmette Guerin(BCG),tetanus toxoid(TT) and a chemokine gene.Olive baboons and BALB/c mice were randomly assigned into vaccine and control groups.The vaccine group animals were primed and boosted twice with pIRES plasmids encoding the SERA5 + BCG + TT alone,or with either CCL5 or CCL20 and the control group with pIRES plasmid vector backbone.Mice and baboons were challenged with P.berghei ANKA and P.knowlesi H strain parasites,respectively.Safety was determined by observing for injection sites reactogenicities,hematology and clinical chemistry.Parasitaemia and survivorship profiles were used to determine cross-species efficacy,and T cell phenotypes,Th1-,Th2-type,T-regulatory immune responses and antibody responses were assessed to determine vaccine immunogenicity.The pSeBCGTT plasmid DNA vaccines were safe and induced Thl-,Th2-type,and Tregulatory responses vaccinated animals showed enhanced CD4~+(P〈0.01),CD 8~+ T cells(P〈 0.001) activation and IgG anti-SE36 antibodies responses(P〈 0.001) at week 4 and 8 post vaccination compared to the control group.Vaccinated mice had a 31.45-68.69%cumulative parasite load reduction and 60%suppression in baboons(P〈0.05)and enhanced survivorship(P〈 0.001) with no clinical signs of malaria compared to the control group.The results showed that the vaccines were safe,immunogenic and conferred partial cross-species protection.
文摘This paper presents an in-host malaria model subject to anti-malarial drug treatment and malaria vaccine antigens combinations.Pontryagin's Maximum Principle is applied to establish optimal control strategies against infected erythrocytes,infected hepatocytes and malaria parasites.Results from numerical simulation reveal that a combination of preerythrocytic vaccine antigen,blood schizontocide and gametocytocide drugs would offer the best strategy to eradicate clinical P.falciparum malaria.Sensitivity analysis,further reveal that the efficacy of blood schizontocides and blood stage vaccines are crucial in the control of clinical malaria infection.Futhermore,we found that an effective blood schizontocide should be used alongside efficacious blood stage vaccine for rapid eradication of infective malaria parasites.The authors hope that the results of this study will help accelerate malaria elimination efforts by combining malaria vaccines and anti-malarial drugs against the deadly P.falciparum malaria.
文摘Objective Four B and Th cell epitopes were selected from conservative domain of Plasmodium falciparum antigens to construct two groups of chimeric malaria DNA vaccines with different configurations and their antigenicities were studied Methods The partially synthesized oligonucleotide was annealed, PCR amplified and cloned into a mammalian cell expression vector By using a pair of isocaudamers on the vector, different single copies of B epitopes were multiplied and were tenderly stringed into two groups of chimeric DNA vaccine with different configurations BALB/c mice were immunized with these DNA plasmids by either intramuscular or intradermal injections Results The antisera from the immunized mice tested by ELISA showed that only the configuration which had a single copy of universal T helper cell epitope, CS T3, located at the C terminal of the multi copy B cell epitopes induced a high antibody response The T helper cell epitope at any other position of the peptide, or the double T helper cell epitopes configured with the B cell epitopes did not enhance antibody response, and some configurations even decreased the humoral response to a B cell epitope Conclusion This study demonstrated that both combination and configuration of the epitope may affect the antigenicity of a chimeric multiple antigen