Animal models for vaccine studies for visceral leishmaniasis.

Visceral leishmaniases (VL) or kala-azar is the most dreaded and devastating amongst the various forms of leishmaniases. The disease, though localized in certain areas only, has gained immense importance because of high mortality rate, mainly in children. The parasite is responsible for a spectrum of clinical syndromes, which can, in most extreme cases, go from an asymptomatic infection to a fatal form of VL. Chemotherapeutic measures, alone are not sufficient to control and contain the disease. As an alternate strategy, vaccination is also under experimental and clinical trails. The situation unquestionably demands the use of proper screening system, rationale chemical synthesis, vaccine development and targeted vaccine delivery. Thus, development of an acceptable vaccine is not an easy task. While the factors, which determine clinical outcomes, are in part, a feature of the parasite, it is the nature of the host and its genetic make up and immune status that play crucial role. The prerequisite of reliable animal model is that it should have a considerably good correlation with the clinical situation and is expected to mimic the pathological features and immunological responses observed in humans when exposed to a variety of Leishmania spp. with different pathogenic characteristics. Many experimental animal models like rodents, dogs and monkeys have been developed, each with specific features, but none accurately reproduces what happens in humans. In addition to the nature of the host, the major difference between natural and experimental infections is the parasite inoculum; in natural conditions, the infected sand fly vector deposits a few hundred metacyclic promastigotes into the dermis of the host, whereas experimental infections are induced by the injection (subcutaneous or intravenous) of millions of promastigotes grown in axenic cultures in vitro or amastigotes recovered from infected spleens. In public health terms, VL is the disease of humans and dogs (which may be considered secondary or 'accidental' hosts in the leishmanial life cycle) who often exhibit severe clinical signs and symptoms when infected, whereas reservoir hosts generally show a few, minor or no signs. This situation makes the definition of a suitable laboratory model a difficult one since the various experimental hosts may behave either like a reservoir or an accidental host. This review discusses the concept of animal models for VL and provides a critical evaluation of the most common experimental models and their respective advantages and disadvantages. Particular emphasis is given to the value of using mouse, hamster, dog and primate models, especially in the context of testing potential antileishmanial vaccines.

Genetically modified live attenuated parasites as vaccines for leishmaniasis.

Leishmaniasis causes significant morbidity and mortality worldwide and is an important public health problem. Even though it is endemic in developing countries in tropical regions of the world,in recent years economic globalization and increased travel has extended its reach to people in developed countries. Leishmania is usually spread by the bite of the female sandfly. In addition, naïve populations can be exposed to Leishmania infection through transfusion of blood and blood products from infected asymptomatic individuals. There are several clinical forms of leishmaniasis caused by different species of the parasite. In some cases, the only possible cure for this disease is drug treatment. However, prolonged use of such drugs has led to parasite drug resistance. At present there are no effective vaccines against Leishmania. Many vaccine strategies have been pursued, including the use of whole cell lysate, killed, avirulent or irradiated parasites. Additionally, DNA vaccines and purified or recombinant parasite antigens have also been tested. Most of these strategies have shown some degree of effectiveness in animal models but little or no protection in humans. There is now a general consensus among Leishmania vaccine researchers that parasite persistence may be important for effective protective response and could be achieved by live attenuated parasite immunization. In this article we reviewed the efforts in developing genetically defined live attenuated Leishmania parasites as vaccine candidates with the goal of achieving a low level of parasite persistence without being virulent in the host and inducing protective immunity.

Vaccine potential of 56-66 kDa protease secreted by Entamoeba histolytica.

Excretory/secretory (ES) antigens and sub-cellular fractions of E. histolytica (HM1:IMSS strain) were tested for the presence of common proteases using substrate gel electrophoresis. We obtained two E. histolytica proteases (56-66 kDa and 29 kDa) from ES material, soluble components and plasma membrane. Protease 56-66 kDa from ES antigen was selected for immunizing hamsters because it gave a consistent broad band. We observed 62.5 per cent protection in immunized animals, compared to 0 per cent in unimmunized controls. Although all vaccinated golden hamsters showed high antibody response, there was no correlation between antibody titres and protection. 56-66 kDa ES protease could thus prevent disease and could be a candidate molecular vaccine against amoebiasis.