The RTS,S/AS02A protein-based vaccine consistently demonstrates significant protection against infection with Plasmodium falciparum malaria and also against clinical malaria and severe disease in children in areas of endemicity. Here we demonstrate with rhesus macaques that priming with a replication-defective human adenovirus serotype 35 (Ad35) vector encoding circumsporozoite protein (CS) (Ad35.CS), followed by boosting with RTS,S in an improved MPL-and QS21-based adjuvant formulation, AS01B, maintains antibody responses and dramatically increases levels of T cells producing gamma interferon and other Th1 cytokines in response to CS peptides. The increased T-cell responses induced by the combination of Ad35.CS and RTS,S/ AS01B are sustained for at least 6 months postvaccination and may translate to improved and more durable protection against P. falciparum infection in humans.Plasmodium falciparum malaria affects millions of people throughout the world annually, and very young children are particularly vulnerable to anemia, cerebral malaria, and death. An effective P. falciparum malaria vaccine could have a profound impact on the lives of the estimated 2 billion at risk (34). The feasibility of development of an effective subunit vaccine against P. falciparum malaria has been convincingly demonstrated by a protein-based antigen (RTS,S), comprising part of the preerythrocytic circumsporozoite (CS) protein, in the AS02A adjuvant system (RTS,S/AS02A; GlaxoSmithKline Biologicals). The RTS,S antigen incorporates part of the CS central tetrapeptide repeat region and C-terminal flanking region, known to contain both B-and T-cell epitopes, into a chimeric gene expressed in Saccharomyces cerevisiae. This construct was named RTS,S to indicate the presence of the CS repeat region (R), T-cell epitopes (T), and hepatitis B virus surface antigen (S) in a mixture of the RTS fusion protein and the S protein that assembles into virus like particles (14, 16).RTS,S formulated in AS02A, a proprietary adjuvant system containing an oil-in-water emulsion and the immune stimulants MPL and QS21, protects approximately 41% of malarianaïve humans against challenge with Plasmodium falciparum sporozoites (18). RTS,S/AS02A efficacy in a field trial was 35% (95% confidence interval [95% CI], 22 to 47%; P Ͻ 0.0001) for protection against first clinical episodes and 49% (95% CI, 12 to 71%; P ϭ 0.02) for protection against severe malaria during an 18-month period for 1-to 4-year-old African children (1, 2). While the unprecedented protection conferred by RTS,S/ AS02A remains partial, several approaches to increasing the efficacy of the vaccine are being studied (16), including new adjuvant formulations and new vaccination strategies.The immune correlates of RTS,S-induced protection are not well defined. However, protection induced by the RTS,S/ AS02A vaccine has been associated with high anti-CS antibody titers, perhaps via inhibition of binding (7) or paralysis of sporozoites (13), or by their opsonization and destruction by phagocytes (32). ...

Abstract. Malaria diagnostics are widely used in epidemiologic studies to investigate natural history of disease and in drug and vaccine clinical trials to exclude participants or evaluate efficacy. The Malaria Laboratory Network (MLN), managed by the Office of HIV/AIDS Network Coordination, is an international working group with mutual interests in malaria disease and diagnosis and in human immunodeficiency virus/acquired immunodeficiency syndrome clinical trials. The MLN considered and studied the wide array of available malaria diagnostic tests for their suitability for screening trial participants and/or obtaining study endpoints for malaria clinical trials, including studies of HIV/ malaria co-infection and other malaria natural history studies. The MLN provides recommendations on microscopy, rapid diagnostic tests, serologic tests, and molecular assays to guide selection of the most appropriate test(s) for specific research objectives. In addition, this report provides recommendations regarding quality management to ensure reproducibility across sites in clinical trials. Performance evaluation, quality control, and external quality assessment are critical processes that must be implemented in all clinical trials using malaria tests.

Summary The performance characteristics of HIV rapid diagnostic tests (RDTs) vary by test and by population. We assessed five commercial RDTs in Uganda where all but one RDT (Determine; Abbott Laboratories, Germany) performed close to manufacturer’s expectations. Determine had low specificity (85.2%, positive predictive value 67.3%) due to false-positive results with weak-positive bands. Properly trained staff, good quality control programmes and validation of RDTs with laboratories having confirmatory testing capacity may be warranted to assure accuracy in each setting.

No abstract