14 research outputs found
A consultation on the optimization of controlled human malaria infection by mosquito bite for evaluation of candidate malaria vaccines.
Early clinical investigations of candidate malaria vaccines and antimalarial medications increasingly employ an established model of controlled human malaria infection (CHMI). Study results are used to guide further clinical development of vaccines and antimalarial medications as CHMI results to date are generally predictive of efficacy in malaria-endemic areas. The urgency to rapidly develop an efficacious malaria vaccine has increased demand for efficacy studies that include CHMI and the need for comparability of study results among the different centres conducting CHMI. An initial meeting with the goal to optimize and standardise CHMI procedures was held in 2009 with follow-up meetings in March and June 2010 to harmonise methods used at different centres. The end result is a standardised document for the design and conduct of CHMI and a second document for the microscopy methods used to determine the patency endpoint. These documents will facilitate high accuracy and comparability of CHMI studies and will be revised commensurate with advances in the field
A consultation on the optimization of controlled human malaria infection by mosquito bite for evaluation of candidate malaria vaccines.
Item does not contain fulltextEarly clinical investigations of candidate malaria vaccines and antimalarial medications increasingly employ an established model of controlled human malaria infection (CHMI). Study results are used to guide further clinical development of vaccines and antimalarial medications as CHMI results to date are generally predictive of efficacy in malaria-endemic areas. The urgency to rapidly develop an efficacious malaria vaccine has increased demand for efficacy studies that include CHMI and the need for comparability of study results among the different centres conducting CHMI. An initial meeting with the goal to optimize and standardise CHMI procedures was held in 2009 with follow-up meetings in March and June 2010 to harmonise methods used at different centres. The end result is a standardised document for the design and conduct of CHMI and a second document for the microscopy methods used to determine the patency endpoint. These documents will facilitate high accuracy and comparability of CHMI studies and will be revised commensurate with advances in the field
Report of a consultation on the optimization of clinical challenge trials for evaluation of candidate blood stage malaria vaccines, 18-19 March 2009, Bethesda, MD, USA.
Item does not contain fulltextDevelopment and optimization of first generation malaria vaccine candidates has been facilitated by the existence of a well-established Plasmodium falciparum clinical challenge model in which infectious sporozoites are administered to human subjects via mosquito bite. While ideal for testing pre-erythrocytic stage vaccines, some researchers believe that the sporozoite challenge model is less appropriate for testing blood stage vaccines. Here we report a consultation, co-sponsored by PATH MVI, USAID, EMVI and WHO, where scientists from all institutions globally that have conducted such clinical challenges in recent years and representatives from regulatory agencies and funding agencies met to discuss clinical malaria challenge models. Participants discussed strengthening and harmonizing the sporozoite challenge model and considered the pros and cons of further developing a blood stage challenge possibly better suited for evaluating the efficacy of blood stage vaccines. This report summarizes major findings and recommendations, including an update on the Plasmodium vivax clinical challenge model, the prospects for performing experimental challenge trials in malaria endemic countries and an update on clinical safety data. While the focus of the meeting was on the optimization of clinical challenge models for evaluation of blood stage candidate malaria vaccines, many of the considerations are relevant for the application of challenge trials to other purposes
Aerosol characterization: comparison between measured and modelled surface radiative forcing over Bay of Bengal
Clearing asymptomatic parasitaemia increases the specificity of the definition of mild febrile malaria
In clinical trials, the specificity of the disease endpoint is critical to an accurate estimate of vaccine efficacy. We used a logistic regression model to analyse parasite densities among children before and after treatment with antimalarials, in order to estimate the impact that clearing asymptomatic parasitaemia had on the specificity of the endpoint of febrile malaria. The malaria attributable fever fraction was higher after antimalarial treatment (i.e. fever and parasitaemia were more likely to be causally related), implying that drug treatment prior to monitoring decreased the misclassification of febrile malaria. In intervention studies with febrile malaria as an endpoint, clearing asymptomatic parasitaemia increases the study's power more effectively than raising the threshold parasitaemia
Synergistic interplay between D2EHPA and TBP towards the extraction of lithium using hollow fiber supported liquid membrane
A human Phase I/IIa malaria challenge trial of a polyprotein malaria vaccine
We examined the safety, immunogenicity and efficacy of a prime-boost vaccination regime involving two poxvirus malaria subunit vaccines, FP9-PP and MVA-PP, expressing the same polyprotein consisting of six pre-erythrocytic antigens from Plasmodium falciparum
A research agenda for malaria eradication: vaccines.
Contains fulltext :
97591.pdf (publisher's version ) (Open Access)Vaccines could be a crucial component of efforts to eradicate malaria. Current
attempts to develop malaria vaccines are primarily focused on Plasmodium
falciparum and are directed towards reducing morbidity and mortality. Continued
support for these efforts is essential, but if malaria vaccines are to be used as
part of a repertoire of tools for elimination or eradication of malaria, they
will need to have an impact on malaria transmission. We introduce the concept of
"vaccines that interrupt malaria transmission" (VIMT), which includes not only
"classical" transmission-blocking vaccines that target the sexual and mosquito
stages but also pre-erythrocytic and asexual stage vaccines that have an effect
on transmission. VIMT may also include vaccines that target the vector to disrupt
parasite development in the mosquito. Importantly, if eradication is to be
achieved, malaria vaccine development efforts will need to target other malaria
parasite species, especially Plasmodium vivax, where novel therapeutic vaccines
against hypnozoites or preventive vaccines with effect against multiple stages
could have enormous impact. A target product profile (TPP) for VIMT is proposed
and a research agenda to address current knowledge gaps and develop tools
necessary for design and development of VIMT is presented
Boosting BCG vaccination with MVA85A down-regulates the immunoregulatory cytokine TGF-β1
In clinical trials recombinant-modified vaccinia virus Ankara expressing the Mycobacterium tuberculosis antigen 85A (MVA85A) induces approximately 10 times more effector T cells than any other recombinant MVA vaccine. We have found that in BCG primed subjects MVA85A vaccination reduces transforming growth factor beta 1 (TGF-β1) mRNA in peripheral blood lymphocytes and reduces TGF-β1 protein in the serum, but increases IFN-γ ELISPOT responses to the recall antigen SK/SD. TGF-β1 is essential for the generation of regulatory T cells and we see a correlation across vaccinees between CD4+CD25hiFoxP3+ cells and TGF-β1 serum levels. This apparent ability to counteract regulatory T cell effects suggests a potential use of MVA85A as an adjuvant for less immunogenic vaccines