Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously, we have shown the potency of recombinant Adenovirus serotype 35 viral vaccines (rAd35) to induce strong immune response against the circumsporozoite protein (CS) of the plasmodium parasite. To further optimize immunogenicity of Ad35-based malaria vaccines we formulated rAd35.CS vaccine with aluminium phosphate adjuvant (AlPO(4)). In contrast to the conventional protein based vaccines no absorption to aluminium adjuvant was observed and rAd35 viral in vitro infectivity in mammalian cells was preserved. Immunization with Ad35.CS formulated with AlPO(4) resulted in significantly higher CS specific T and B cell responses in mice upon either single or prime-boost vaccination regimens as compared to rAd35.CS alone. With these results we report for the first time the feasibility of using an AlPO(4) adjuvant to increase the potency of a live adenovirus serotype 35-based vaccine.
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PMID:Increased immunogenicity of recombinant Ad35-based malaria vaccine through formulation with aluminium phosphate adjuvant. 1764 36

The difficulty of inducing protective immunity through antibodies against sporozoites led to efforts to assess vectored vaccines as a means of inducing protective T-cell immunity against the malaria liver-stage parasite. Although DNA vectored vaccines used alone were poorly immunogenic and not protective, high levels of parasite clearance in the liver has been achieved with viral vectored vaccines used in heterologous prime-boost regimes. Such vectored vaccination regimes represent one of only two approaches that have induced repeatable partial efficacy in human P. falciparum subunit vaccine trials. Interestingly, vectors expressing the TRAP antigen have been consistently been more immunogenic and protective than vectors expressing the circumsporozoite protein in human trials. However, sterile protection requires induction of very potent T-cell responses that are currently only achievable with heterologous prime-boost regimes. Recently, simian adenoviruses have been assessed as priming agents in Adenovirus-MVA regimes in both phase I and phase IIa trials in the UK, based on very promising pre-clinical results showing better immunogenicity and efficacy than previous prime-boost regimes. The same vectors are also being assessed clinically expressing blood-stage antigens, attempting to induce both protective antibodies and T cells as recently demonstrated in murine efficacy studies. These viral vectors now provide a major option for inclusion in a high efficacy multi-stage malaria vaccine that should achieve deployable levels of efficacy in endemic settings.
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PMID:Prime-boost vectored malaria vaccines: progress and prospects. 2006 2

Adenovirus particles can be engineered to display exogenous peptides on their surfaces by modification of viral capsid proteins, and particles that display pathogen-derived peptides can induce protective immunity. We constructed viable recombinant adenoviruses that display B-cell epitopes from the Plasmodium falciparum circumsporozoite protein (PfCSP) in the major adenovirus capsid protein, hexon. Recombinants induced high-titer antibodies against CSP when injected intraperitoneally into mice. Serum obtained from immunized mice recognized both recombinant PfCSP protein and P. falciparum sporozoites, and neutralized P. falciparum sporozoites in vitro. Replicating adenovirus vaccines have provided economical protection against adenovirus disease for over three decades. The recombinants described here may provide a path to an affordable malaria vaccine in the developing world.
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PMID:Adenovirus particles that display the Plasmodium falciparum circumsporozoite protein NANP repeat induce sporozoite-neutralizing antibodies in mice. 2119 7

Protection against malaria through vaccination is known to be achievable, as first demonstrated over 30 years ago. Vaccination via repeated bites with Plasmodium falciparum infected and irradiated mosquitoes provided short lived protection from malaria infection to these vaccinees. Though this method still remains the most protective malaria vaccine to date, it is likely impractical for widespread use. However, recent developments in sub-unit malaria vaccine platforms are bridging the gap between high levels of protection and feasibility. The current leading sub-unit vaccine, RTS,S (which consists of a fusion of a portion of the P. falciparum derived circumsporozoite protein to the Hepatitis B surface antigen), has demonstrated the ability to induce protection from malaria infection in up 56% of RTS,S vaccinees. Though encouraging, these results may fall short of protection levels generally considered to be required to achieve eradication of malaria. Therefore, the use of viral vectored vaccine platforms has recently been pursued to further improve the efficacy of malaria targeted vaccines. Adenovirus based vaccine platforms have demonstrated potent anti-malaria immune responses when used alone, as well when utilized in heterologous prime boost regimens. This review will provide an update as to the current advancements in malaria vaccine development, with a focus on the use of adenovirus vectored malaria vaccines.
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PMID:Malaria vaccines: focus on adenovirus based vectors. 2268 63

Malaria remains a significant global health burden and a vaccine would make a substantial contribution to malaria control. Chimpanzee Adenovirus 63 Modified Vaccinia Ankara Multiple epitope thrombospondin adhesion protein (ME-TRAP) and vaccination has shown significant efficacy against malaria sporozoite challenge in malaria-naive European volunteers and against malaria infection in Kenyan adults. Infants are the target age group for malaria vaccination; however, no studies have yet assessed T-cell responses in children and infants. We enrolled 138 Gambian and Burkinabe children in four different age-groups: 2-6 years old in The Gambia; 5-17 months old in Burkina Faso; 5-12 months old, and also 10 weeks old, in The Gambia; and evaluated the safety and immunogenicity of Chimpanzee Adenovirus 63 Modified Vaccinia Ankara ME-TRAP heterologous prime-boost immunization. The vaccines were well tolerated in all age groups with no vaccine-related serious adverse events. T-cell responses to vaccination peaked 7 days after boosting with Modified Vaccinia Ankara, with T-cell responses highest in 10 week-old infants. Heterologous prime-boost immunization with Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara ME-TRAP was well tolerated in infants and children, inducing strong T-cell responses. We identify an approach that induces potent T-cell responses in infants, which may be useful for preventing other infectious diseases requiring cellular immunity.
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PMID:Safety and Immunogenicity of ChAd63 and MVA ME-TRAP in West African Children and Infants. 2710 30

Adenovirus (Ad) is thought to be one of the most promising platforms for a malaria vaccine targeted against its liver stages, because of its ability to induce a strong T-cell response against a transgene. However, a further improvement of this platform is needed in order to elicit another arm of the immunity, i.e. humoral response, against malaria. In order to augment immunogenicity and protective efficacy of Ad-based malaria vaccine, we inserted B-cell, as well as CD4+ T-cell, epitopes of Plasmodium falciparum circumsporozoite protein (PfCSP) into the capsid protein, Hexon, and the core protein, VII (pVII), of Ad, respectively, in addition to the PfCSP transgene. Insertion of PfCSP-derived B cell epitope to Hexon significantly enhanced the epitope-specific antibody response compared to AdPfCSP, an Ad vaccine expressing only PfCSP transgene. PfCSP-derived CD4+ T-cell epitope insertion into pVII augmented not only PfCSP-specific CD4+ T-cell response but also anti-PfCSP antibody response. Finally, mice immunized with AdPfCSP having both Hexon and pVII modifications were more protected than AdPfCSP or Hexon-modified AdPfCSP against challenge with transgenic rodent malaria parasites expressing the PfCSP. Overall, this study has demonstrated that Hexon and pVII-modified AdPfCSP vaccine is a promising malaria vaccine which induces strong PfCSP-specific humoral, CD4+ T-cell, and CD8+ T-cell responses and protects against infection with transgenic malaria parasites expressing the PfCSP.
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PMID:A potent malaria vaccine based on adenovirus with dual modifications at Hexon and pVII. 2908 94