Correlating efficacy and immunogenicity in malaria vaccine trials.

The availability of an effective and appropriately implemented malaria vaccine would form a crucial cornerstone of public health efforts to fight this disease. Despite many decades of research, however, no malaria vaccine has yet shown satisfactory protective efficacy or been rolled-out. Validated immunological substitute endpoints have the potential to accelerate clinical vaccine development by reducing the required complexity, size, duration and cost of clinical trials. Besides facilitating clinical development of existing vaccine candidates, understanding immunological mechanisms of protection may drive the development of fundamentally new vaccination approaches. In this review we focus on correlates of protection in malaria vaccine development: Does immunogenicity predict malaria vaccine efficacy and why is this question particularly difficult? Have immunological correlates accelerated malaria vaccine development in the past and will they facilitate it in the future? Does Controlled Human Malaria Infection represent a valid model for identifying such immunological correlates, or a correlate of protection against naturally-acquired malaria in itself?

[Achievements and perspectives of research into development of a vaccine against malaria]. / Osiagniecia i perspektywy w badaniach nad opracowaniem szczepionki przeciwko malarii.

Malaria is caused by parasites of the genus Plasmodium. Every year from 350 to 500 million of malaria cases are recorded with an estimated annual death toll of over 1.1 million deaths, making malaria the global health problem. Malaria deepens the poverty, limits the education and causes absences at schools and workplaces--what makes the progress of civilization and economy slower. This is why beside the classical methods of malaria prevention, such as the elimination of the places of mosquito breeding and, application of insecticides or chemoprophylaxis, the elaboration of effective malaria vaccine is a necessity. Despite considerably high financial investments for long term malaria research, so far it has not been possible to develop an efficient vaccine against this disease. This is why the main topic of the present review is presenting of achievements and perspectives of research on development of vaccine against malaria with special consideration of tested antigens. Our review also contains an attempt to typify the most prospective vaccine. Currently developed and tested vaccines against malaria may be divided in three groups depending on the parasite living stage which the vaccine influences: pre-erythrocytic stage vaccines, blood stage vaccines and transmission blocking vaccines. At the moment it seems that the most promising vaccine against malaria is RTS,S/ASO2A which represent the pre-erythrocytic stage vaccines. However developing a completely safe, efficient and budget-friendly vaccine still remains the far-reaching goal and requires further years of research.

The malaria vaccine development program in Papua New Guinea.

Through a collaborative project led by the Papua New Guinea Institute of Medical Research (PNGIMR), Papua New Guinea has a significant role in the global effort to develop a malaria vaccine, ensuring that the malaria patterns in Asia and the Pacific region are considered in vaccine development strategies. Some of the major perspectives and achievements of the program are discussed here, one of the most successful being the trial of Combination B, a vaccine comprising three asexual blood-stage proteins [merozoite surface protein (MSP)1, MSP2 and ring-infected erythrocyte surface antigen (RESA)], which led to a considerable reduction of parasite density in the immunized children.

Progress with new malaria vaccines.

Malaria is a parasitic disease of major global health significance that causes an estimated 2.7 million deaths each year. In this review we describe the burden of malaria and discuss the complicated life cycle of Plasmodium falciparum, the parasite responsible for most of the deaths from the disease, before reviewing the evidence that suggests that a malaria vaccine is an attainable goal. Significant advances have recently been made in vaccine science, and we review new vaccine technologies and the evaluation of candidate malaria vaccines in human and animal studies worldwide. Finally, we discuss the prospects for a malaria vaccine and the need for iterative vaccine development as well as potential hurdles to be overcome.

[Antimalarial vaccination]. / La vaccination antipalustre.

The vaccination against malaria is very difficult due to the complexity and variability of the malaria antigens and the imperfection of the available experimental models. During the last 20 years, especially since the first in vitro cultures of Plasmodium falciparum, several types of vaccines have been tried. These vaccines are directed against the sporozoites, against the merozoites or against the gametocytes. Each of the vaccines corresponds to a vaccine conception and to some well-defined goals. Despite the large number of studies, sometimes with considerable means, all of the trials have failed. In contrast, the recent work of Patarroyo, and some diverse collaborating teams, have at least partially succeeded. Vaccine trials in several countries of South America and East Africa, using the synthetic antigen SPf 66, provided protection of 30 to 50%. These results are still modest but its to their credit to be the first successful antimalaria vaccine in humans. Also, these results were evaluated by their effects on morbidity and not only on parasitaemia. Some important progress remains to be accomplished, but a decisive step has been surmounted. Also, other types of vaccines will be tried soon. They differ by their target or by their conception, notably for the anti-DNA vaccines. One or several efficient vaccines should be available within the next few years. However, no one can determine the length of the waiting period. It is unrealistic to give this vaccine all of the hopes of eradication or even control of malaria in the endemic zones. A disease epidemiologically so complex as malaria cannot be eliminated by one procedure. The success will be obtained with the judicious use of the sum of the currently available means, including antivectorial fight and protection, drug prophylaxis and drug therapy, in addition to the vaccine when it is available.

The Malaria Vaccine Epidemiology and Evaluation Project of Papua New Guinea: rationale and baseline studies.

The range of possible malaria vaccines, against different species of Plasmodium and various stages in the life cycle of the parasite in both human host and mosquito vector, is reviewed. The importance, in a malaria-endemic area, of protection by a malaria vaccine against disease rather than infection is emphasized, and the ways by which disease prevention may be achieved are discussed. Mechanisms of production and presentation of vaccines are considered, including the importance of appropriate and more effective adjuvants. The variety of immune responses to malaria is set out and linked to both human and plasmodial genetic factors. Host genetics may also modify susceptibility to malaria through mechanisms which are not immunological. There is a need for entomological studies of the Anopheles vectors, especially but not only in preparation for transmission-blocking vaccines. This overall complexity justifies a multidimensional approach to epidemiology and field-site preparation. An iterative procedure is proposed for initial field evaluation, through adult male volunteers to community studies in immune adults and then to semi-immune school children, before evaluation in the principal target population of nonimmune young children. The outcome variables for epidemiological evaluation are specified. After this brief review of malaria vaccines, the baseline studies being undertaken by the Malaria Vaccine Epidemiology and Evaluation Project of the Papua New Guinea Institute of Medical Research in the Wosera area of East Sepik Province are discussed in some detail, and their rationale linked to the range and complexity of the malaria vaccines that have been reviewed. These studies are described under the headings of their principal components of epidemiology, parasitology, immunology, genetics and entomology.

Vaccine strategies for malaria: applicability in areas of seasonal or epidemic malaria.

The likely effects of different vaccine strategies was tested using computer simulation of malaria transmission. In areas of seasonal or epidemic malaria, vaccines directed against all stages (pre-erythrocytic, erythrocytic and sexual) gave similar reductions in disease transmission. These models indicate that such vaccines may be much more effective that commonly predicted. The major effect will be to slow the spread of, rather than totally prevent malaria. As such, the use of such vaccines will be heavily dependent on integrated control programs involving other forms of control.