Protection Induced by Plasmodium falciparum MSP142 Is Strain-Specific, Antigen and Adjuvant Dependent, and Correlates with Antibody Responses

Vaccination with Plasmodium falciparum MSP142/complete Freund's adjuvant (FA) followed by MSP142/incomplete FA is the only known regimen that protects Aotus nancymaae monkeys against infection by erythrocytic stage malaria parasites. The role of adjuvant is not defined; however complete FA cannot be used in humans. In rodent models, immunity is strain-specific. We vaccinated Aotus monkeys with the FVO or 3D7 alleles of MSP142 expressed in Escherichia coli or with the FVO allele expressed in baculovirus (bv) combined with complete and incomplete FA, Montanide ISA-720 (ISA-720) or AS02A. Challenge with FVO strain P. falciparum showed that suppression of cumulative day 11 parasitemia was strain-specific and could be induced by E. coli expressed MSP142 in combination with FA or ISA-720 but not with AS02A. The coli42-FVO antigen induced a stronger protective effect than the bv42-FVO antigen, and FA induced a stronger protective effect than ISA-720. ELISA antibody (Ab) responses at day of challenge (DOC) were strain-specific and correlated inversely with c-day 11 parasitemia (r = −0.843). ELISA Ab levels at DOC meeting a titer of at least 115,000 ELISA Ab units identified the vaccinees not requiring treatment (noTx) with a true positive rate of 83.3% and false positive rate of 14.3 %. Correlation between functional growth inhibitory Ab levels (GIA) and cumulative day 11 parasitemia was weaker (r = −0.511), and was not as predictive for a response of noTx. The lowest false positive rate for GIA was 30% when requiring a true positive rate of 83.3%. These inhibition results along with those showing that antigen/FA combinations induced a stronger protective immunity than antigen/ISA-720 or antigen/AS02 combinations are consistent with protection as ascribed to MSP1-specific cytophilic antibodies. Development of an effective MSP142 vaccine against erythrocytic stage P. falciparum infection will depend not only on antigen quality, but also upon the selection of an optimal adjuvant component

The Role of Leptospirosis Reference Laboratories

The general goal of reference centres is to support the community, from diagnostic laboratories to research institutions, in the execution of their work by providing reference strains and reagents and giving instructions and recommendations to individual colleagues and national and international organisations on a wide variety of issues. There are different levels of reference centres, from local to international, with an increasing package of tasks and responsibilities. Local reference centres might limit activities to diagnostic confirmation by applying standard testing, while international reference centres cover a wider range of activities from design, validation and harmonisation of diagnostic and reference technologies to international monitoring associated with recommendations on the global burden and distribution of leptospirosis and its prevention and control to national and international health decision makers. This chapter focusses on four major pillars constituting reference tasks in addition to the obvious provision of reference substances, i.e. Research and training, Diagnosis, Identification of Leptospira and Surveillance. Due to financial and organisational constraints, reference centres are restricted in their capacity for basic research and consequently focus on applied research into various aspects of leptospirosis. They offer training, either individually or group-wise, that might vary from standard technologies to novel sophisticated methodologies, depending on the need and requests of the trainee. Most reference centres are involved in the confirmation of preliminary diagnosis obtained at peripheral levels, such as local hospitals and health centres, while other major activities involve the design and validation of diagnostics, their international harmonisation and quality assurance. Identification of causative Leptospira strains (or serovars) is key to the identification of infection sources and is critical for surveillance. Hence, reference centres also focus on the development, application and provision of methods that are required for unambiguous characterisation of new and recognised Leptospira strains and the maintenance of the integrity of strain collections. In line with their central role, reference centres are frequently associated with local, national and/or international surveillance activities linked to an advisory role and the production of guidelines. Such surveillance activities usually comprise collation of morbidity and mortality data, signalling of outbreaks and the investigation of infection sources and risk