Immune responses to malaria pre‐erythrocytic stages: Implications for vaccine development

Abuga, Kelvin M.; Jones‐Warner, William; Hafalla, Julius Clemence R.

doi:10.1111/pim.12795

Cited by 14 publications

(9 citation statements)

References 179 publications

(387 reference statements)

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“…The main objective for developing a vaccine against the pre-erythrocytic stage is to inhibit hepatocyte infections and the development of the hepatic parasite, thus limiting the invasion of red blood cells [ 38 ]. Importantly, protection of sporozoites from malaria may depend on a fine balance of both innate and adaptive immune responses present in the pre-erythrocytic stages [ 39 ]. It is widely recognized that an effective, long-lasting malaria vaccine will need to induce robust antibody and T cell responses.…”

Section: Resultsmentioning

confidence: 99%

A Review of Major Patents on Potential Malaria Vaccine Targets

et al. 2023

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Malaria is a parasitic infection that is a great public health concern and is responsible for high mortality rates worldwide. Different strategies have been employed to improve disease control, demonstrating the ineffectiveness of controlling vectors, and parasite resistance to antimalarial drugs requires the development of an effective preventive vaccine. There are countless challenges to the development of such a vaccine directly related to the parasite’s complex life cycle. After more than four decades of basic research and clinical trials, the World Health Organization (WHO) has recommended the pre-erythrocytic Plasmodium falciparum (RTS, S) malaria vaccine for widespread use among children living in malaria-endemic areas. However, there is a consensus that major improvements are needed to develop a vaccine with a greater epidemiological impact in endemic areas. This review discusses novel strategies for malaria vaccine design taking the target stages within the parasite cycle into account. The design of the multi-component vaccine shows considerable potential, especially as it involves transmission-blocking vaccines (TBVs) that eliminate the parasite’s replication towards sporozoite stage parasites during a blood meal of female anopheline mosquitoes. Significant improvements have been made but additional efforts to achieve an efficient vaccine are required to improve control measures. Different strategies have been employed, thus demonstrating the ineffectiveness in controlling vectors, and parasite resistance to antimalarial drugs requires the development of a preventive vaccine. Despite having a vaccine in an advanced stage of development, such as the RTS, S malaria vaccine, the search for an effective vaccine against malaria is far from over. This review discusses novel strategies for malaria vaccine design taking into account the target stages within the parasite’s life cycle.

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Section: Resultsmentioning

confidence: 99%

A Review of Major Patents on Potential Malaria Vaccine Targets

et al. 2023

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“…The main objective for developing a vaccine against the pre-erythrocytic stage is to inhibit hepatocyte infections and the development of the hepatic parasite, thus limiting the invasion of red blood cells [36]. Importantly, protection of sporozoites from malaria may depend on a fine balance of both innate and adaptive immune responses present in the pre-erythrocytic stages [37]. It is widely recognized that an effective, long-lasting malaria vaccine will need to induce robust antibody and T cell responses.…”

Section: Pre-erythrocytic Stagementioning

confidence: 99%

A Review of Major Patents on Potential Malaria Vaccine Targets, Including Antigens from Different Stages of The Parasite Cycle

Mariano¹,

Gonçalves²,

Oliveira³

et al. 2023

Preprint

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Malaria is a parasitic infection that is a great public health concern and is responsible for high mortality rates worldwide. Different strategies have been employed to improve disease control, demonstrating the ineffectiveness of controlling vectors, and parasite resistance to antimalarial drugs requires the development of an effective preventive vaccine. There are countless challenges to the development of such a vaccine directly related to the parasite's complex life cycle. After more than four decades of basic research and clinical trials, the World Health Organization (WHO) has recommended the pre-erythrocytic Plasmodium falciparum (RTS, S) malaria vaccine for widespread use among children living in malaria-endemic areas. However, there is a consensus that major improvements are needed to develop a vaccine with a greater epidemiological impact in endemic areas. This review discusses novel strategies for malaria vaccine design taking the target stages within the parasite cycle into account. The design of the multi-component vaccine shows considerable potential, especially as it involves transmission-blocking vaccines (TBVs) that eliminate the parasite's replication towards sporozoite stage parasites during a blood meal of female anopheline mosquitoes. Significant improvements have been made but additional efforts to achieve an efficient vaccine are required to improve control measures. Different strategies have been employed, thus demonstrating the ineffectiveness in controlling vectors, and parasite resistance to antimalarial drugs requires the development of a preventive vaccine. Despite having a vaccine in an advanced stage of development, such as the RTS, S malaria vaccine, the search for an effective vaccine against malaria is far from over. This review discusses novel strategies for malaria vaccine design taking into account the target stages within the parasite’s life cycle.

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“…One possible mechanism is that TH2R-TH3R strain specific cytotoxic T cells (C8+) are engendered by the vaccine and contribute to efficacy by killing infected hepatocytes. Cytotoxic CD8 T cells are known to be key effectors in mouse models of attenuated sporozoite and in human whole sporozoite responses [60]. RTS,S is not formulated to drive a cytotoxic response, and measures of CD8 have been absent or low and thought to be relatively inconsequential [61].…”

Section: Ecologymentioning

confidence: 99%

Impacts of Ecology, Parasite Antigenic Variation, and Human Genetics on RTS,S/AS01e Malaria Vaccine Efficacy

et al. 2021

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Purpose of Review Global malaria elimination has little chance of success without an effective vaccine. The first malaria vaccine, RTS,S/AS01e, demonstrated moderate efficacy against clinical malaria in phase III trials and is undergoing large-scale effectiveness trials in Africa. Importantly, the vaccine did not perform equally well between phase III study sites. Though reasons for the moderate efficacy and this variation are unclear, various mechanisms have been suggested. This review summarizes the recent literature on such mechanisms, with a focus on those involving landscape ecology, parasite antigenic variation, and human host genetic differences. Recent Findings Transmission intensity may have a role pre- and post-vaccination in modulating immune responses to the vaccine. Furthermore, malaria incidence may “rebound” in vaccinated populations living in high transmission intensity settings. There is growing evidence that both genetic variation in the parasite circumsporozoite protein and variation of human host genetic factors affect RTS,S vaccine efficacy. These genetic factors may be interacting in complex ways to produce variation in the natural and vaccine-induced immune responses that protect against malaria. Summary Due to the modest efficacy of RTS,S/AS01e, the combinations of factors (ecological, parasite, human host) impacting its effectiveness must be clearly understood, as this information will be critical for implementation policy and future vaccine designs.

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Immune responses to malaria pre‐erythrocytic stages: Implications for vaccine development

Cited by 14 publications

References 179 publications

A Review of Major Patents on Potential Malaria Vaccine Targets

A Review of Major Patents on Potential Malaria Vaccine Targets

A Review of Major Patents on Potential Malaria Vaccine Targets, Including Antigens from Different Stages of The Parasite Cycle

Impacts of Ecology, Parasite Antigenic Variation, and Human Genetics on RTS,S/AS01e Malaria Vaccine Efficacy

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