The Challenge of Parasite Control
Eric S. Loker, Bruce V. Hofkin in Parasitology, 2023
The development of an anti-malaria vaccine has been something of a holy grail in vaccine research. Malaria is notoriously difficult to control through more conventional means, and the emergence of multi-drug resistant Plasmodium strains only highlights the need for a safe, economical, and effective vaccine. Modern efforts to develop such a vaccine accelerated in the 1970s when William Trager developed in vitro methods for the maintenance of the P. falciparum life cycle. This development suddenly provided researchers with an essentially limitless amount of blood-stage parasite material for experimental purposes. In spite of decades of rigorous and concentrated research, however, only one anti-malaria vaccine is currently available for use, and as we will discuss shortly, it is far from perfect. Yet although obstacles to malaria vaccines are numerous, there is still reason for optimism.
The Future Of Parasitology
Eric S. Loker, Bruce V. Hofkin in Parasitology, 2015
Malaria provides a good example (see Chapter 9). A tremendous amount of research has brought a new malaria vaccine to clinical trial and, although it can protect about 50% of the recipients from more severe clinical episodes (which is a significant accomplishment), much remains to be done before there is a malaria vaccine that will have the effect of preventing and eventually eliminating transmission in endemic areas. As discussed in detail in Chapter 9, what we have learned is that malaria parasites, and indeed other eukaryotic parasites such as helminths, present considerably more difficulties to the immunologist than do many viral or bacterial pathogens with respect to development of effective vaccines. To be woven into the already complex tapestry of vaccine research should be increased appreciation of the evolutionary biology of parasites. For example, it has recently been noted that parasites may be selected to display immunodominant antigens that provoke immune pathways that lead to ineffectual or strain-specific immune responses. Instead, we need to find and target parasite antigens that are perhaps disguised or more conserved that provoke more effective and less strain-specific killing responses. As noted earlier in the chapter, vaccination efforts might also unwittingly favor more virulent forms of malaria parasites. If a vaccine is effective, it is likely that the selection on parasites to overcome it will be strong, and so it seems likely that a continuing effort will be required to maintain effective vaccines.
From Malaria Eradication to Malaria Control
E. J. Clegg, J. P. Garlick in Disease and Urbanization, 1980
Our technical means of controlling, let alone eradicating, malaria in many endemic areas of the world are inadequate. A concentrated research effort may find new ways to attack the malaria parasite and its vector. Fields in which research is felt to be particularly important include the improvement of immunological surveillance techniques, study of the behaviour of mosquito vectors and their resistance to insecticides, better and more acceptable insecticides, and the development of new antimalarial drugs. Much has been said and written about the possibility of a prospective malaria vaccine, but the present experimental results, however encouraging, show the practical difficulties of this method. It seems that synthetic antimalarial drugs will be our most reliable weapon for many years. Nevertheless, research in the feasibility of malaria vaccine should be stimulated and supported.
Malaria vaccines in the eradication era: current status and future perspectives
Published in Expert Review of Vaccines, 2019
K. L. Wilson, K. L. Flanagan, M. D. Prakash, M. Plebanski
The agenda has been set to not just control, but to eradicate malaria from the world; a lofty goal fraught with challenges. Despite this aim, malaria continues to present a significant global heath burden, with an estimated 216 million cases occurring worldwide in 2016, resulting in 445,000 deaths [1]. Treatment for malaria relies on antimalarial drugs, but drug resistance develops to each newly introduced antimalarial agent [1]. Malaria control measures include the wide deployment of impregnated bed nets and insecticide spraying, which contribute to an overall reduced incidence of malaria. These measures are not sufficient alone, due in part to their incomplete use in malaria-endemic regions, as well as the development of resistance to insecticides. Therefore, a long-lasting malaria vaccine is urgently needed. However, despite decades of intensive research only one candidate vaccine has been licensed for use in humans, the recombinant pre-erythrocytic vaccine RTS, S/AS01 [2]. In the present review we will offer a general updated overview of the malaria vaccine field and discuss in some detail the issues associated with trying to provide effective, eradication capable, potentially multistage vaccines from an immunological viewpoint. The review focuses on human vaccine trials, with a major emphasis on cell mediated immune mechanisms that might be harnessed to achieve effective long-lasting immunity. The role of vaccine-induced antibodies has been comprehensively reviewed in two recent publications [3,4] and will not be discussed.
Biological strategies and political hurdles in developing malaria vaccines
Published in Expert Review of Vaccines, 2021
Michael F. Good, Danielle I. Stanisic
A further unique issue for malaria vaccine development applies to immunity to the sexual-stages of the parasite. This immunity, referred to as ‘transmission-blocking’ immunity, aims to kill the gametes or zygotes in the mosquito mid-gut via antibodies taken up by the feeding mosquito. Thus, unlike sporozoite/liver-stage and blood-stage vaccines, a sexual-stage vaccine will not directly protect the vaccinated individual from contracting malaria but will prevent the vaccinee from passing the malaria parasite to another person. All malaria vaccines have the ability to have an impact on the transmission of the parasite. By reducing the parasite burden in the blood or limiting infection duration, a blood-stage vaccine will lead to fewer gametocytes and reduced transmission and a sporozoite vaccine with 100% efficacy will completely prevent transmission. However, vaccines that intentionally target the sexual-stage of the parasite and aim to prevent development of the malaria parasite in the mosquito midgut are also being developed [14]. Structure-based vaccine design may facilitate the induction of an enhanced and more focused antibody response against sexual-stage antigens associated with potent inhibitory activity in the mosquito [15].
In vitro antiplasmodial activity, hemocompatibility and temporal stability of Azadirachta indica silver nanoparticles
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2022
Joseph Hawadak, Loick Pradel Kojom Foko, Veena Pande, Vineeta Singh
Malaria is an endemic disease of the intertropical regions caused by a protozoan belonging to the genus Plasmodium and transmitted to human through infected female Anopheles mosquito. According to World Health Organization (WHO), 241 million malaria cases were recorded worldwide in 2020, with 82.2% of cases in the sub-Saharan African (sSA) region [1]. The fight against this disease includes prophylaxis, regular screening and early treatment mainly in children under five years of age and pregnant women, the main vulnerable targets. The coverage use of insecticide-treated mosquito nets ∼65% in sSA is constantly increasing with a satisfactory impact [1]. Artemisinin-based combination therapies (ACT) recommended by WHO remain the most effective antimalarial till date even though resistance has been reported from some South Asian and African regions [2,3]. No effective vaccine for malaria is available currently, though clinical trial results of RTS, S/AS01 vaccine are promising and new generation malaria vaccines (e.g.: R21/Matrix-M) are already in clinical phases [4]. In sSA countries, the low standards of living and the lack of good quality anti-malarial drugs would be the limiting factors for malaria elimination programs [1–3,5].
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