-
The Journal of Clinical Investigation Jan 2022
Review
Topics: Humans; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum
PubMed: 34981788
DOI: 10.1172/JCI156588 -
BioDrugs : Clinical Immunotherapeutics,... Nov 2023Malaria is a mosquito-borne disease caused by protozoan parasites of the genus Plasmodium. Despite significant declines in malaria-attributable morbidity and mortality... (Review)
Review
Malaria is a mosquito-borne disease caused by protozoan parasites of the genus Plasmodium. Despite significant declines in malaria-attributable morbidity and mortality over the last two decades, it remains a major public health burden in many countries. This underscores the critical need for improved strategies to prevent, treat and control malaria if we are to ultimately progress towards the eradication of this disease. Ideally, this will include the development and deployment of a highly effective malaria vaccine that is able to induce long-lasting protective immunity. There are many malaria vaccine candidates in development, with more than a dozen of these in clinical development. RTS,S/AS01 (also known as Mosquirix) is the most advanced malaria vaccine and was shown to have modest efficacy against clinical malaria in phase III trials in 5- to 17-month-old infants. Following pilot implementation trials, the World Health Organisation has recommended it for use in Africa in young children who are most at risk of infection with P. falciparum, the deadliest of the human malaria parasites. It is well recognised that more effective malaria vaccines are needed. In this review, we discuss malaria vaccine candidates that have progressed into clinical evaluation and highlight the most advanced candidates: Sanaria's irradiated sporozoite vaccine (PfSPZ Vaccine), the chemoattenuated sporozoite vaccine (PfSPZ-CVac), RTS,S/AS01 and the novel malaria vaccine candidate, R21, which displayed promising, high-level efficacy in a recent small phase IIb trial in Africa.
Topics: Infant; Animals; Child; Humans; Child, Preschool; Malaria Vaccines; Plasmodium falciparum; Malaria, Falciparum; Malaria; Sporozoites
PubMed: 37728713
DOI: 10.1007/s40259-023-00623-4 -
Current Opinion in Microbiology Dec 2022The complex Plasmodium life cycle offers different vaccine approaches with distinct parasitological and clinical effects. The approaches and their rationales were... (Review)
Review
The complex Plasmodium life cycle offers different vaccine approaches with distinct parasitological and clinical effects. The approaches and their rationales were established decades ago: vaccines targeting pre-erythrocytic (sporozoite and liver-stage) parasites prevent infection, those to blood-stage parasites reduce disease, and those to sexual-stage parasites or mosquito vector reduce transmission and eliminate malaria through herd immunity. The pre-erythrocytic RTS,S vaccine (Mosquirix, GlaskoSmithKline (GSK)), recommended by WHO in 2021, reduces clinical malaria in children. Knowledge of parasite biology, host-parasite interactions, and immune mechanisms is informing new concepts to improve on RTS,S and to target other parasite stages. This review emphasizes vaccine approaches and candidates currently in the clinic or likely to enter clinical testing soon.
Topics: Animals; Child; Humans; Malaria Vaccines; Sporozoites; Plasmodium; Malaria
PubMed: 36343566
DOI: 10.1016/j.mib.2022.102227 -
Expert Review of Vaccines 2023Malaria, a devastating febrile illness caused by protozoan parasites, sickened 247,000,000 people in 2021 and killed 619,000, mostly children and pregnant women in... (Review)
Review
INTRODUCTION
Malaria, a devastating febrile illness caused by protozoan parasites, sickened 247,000,000 people in 2021 and killed 619,000, mostly children and pregnant women in sub-Saharan Africa. A highly effective vaccine is urgently needed, especially for (Pf), the deadliest human malaria parasite.
AREAS COVERED
Sporozoites (SPZ), the parasite stage transmitted by mosquitoes to humans, are the only vaccine immunogen achieving >90% efficacy against Pf infection. This review describes >30 clinical trials of PfSPZ vaccines in the U.S.A., Europe, Africa, and Asia, based on first-hand knowledge of the trials and PubMed searches of 'sporozoites,' 'malaria,' and 'vaccines.'
EXPERT OPINION
First generation (radiation-attenuated) PfSPZ vaccines are safe, well tolerated, 80-100% efficacious against homologous controlled human malaria infection (CHMI) and provide 18-19 months protection without boosting in Africa. Second generation chemo-attenuated PfSPZ are more potent, 100% efficacious against stringent heterologous (variant strain) CHMI, but require a co-administered drug, raising safety concerns. Third generation, late liver stage-arresting, replication competent (LARC), genetically-attenuated PfSPZ are expected to be both safe and highly efficacious. Overall, PfSPZ vaccines meet safety, tolerability, and efficacy requirements for protecting pregnant women and travelers exposed to Pf in Africa, with licensure for these populations possible within 5 years. Protecting children and mass vaccination programs to block transmission and eliminate malaria are long-term objectives.
Topics: Pregnancy; Child; Animals; Humans; Female; Sporozoites; Translational Science, Biomedical; Malaria Vaccines; Vaccines, Attenuated; Malaria; Malaria, Falciparum; Plasmodium falciparum; Immunization
PubMed: 37571809
DOI: 10.1080/14760584.2023.2245890 -
Expert Review of Vaccines Feb 2021: The development of effective vaccines remains a major health priority to combat the global burden of malaria, a life-threatening disease caused by parasites.... (Review)
Review
: The development of effective vaccines remains a major health priority to combat the global burden of malaria, a life-threatening disease caused by parasites. Transmission-blocking vaccines (TBVs) elicit antibodies that neutralize the sexual stages of the parasite in blood meals ingested by the mosquito, interrupting parasite development in the vector host and preventing disease spread to other individuals.: The gametocyte surface antigens Pfs230, Pfs48/45, and Pfs47, the parasite ookinete surface protein Pfs25, and the male gametocyte specific protein PfHAP2 are leading TBV candidates, some of which are in clinical development. The recent expansion of methodology to study monoclonal antibodies isolated directly from humans and animal models, coupled with effective measures for parasite neutralization, has provided unprecedented insight into TBV efficacy and development.: Available structural and functional data on antigen-monoclonal antibody (Ag-mAb) complexes, as well as epitope classification studies, have identified neutralizing epitopes that may aid vaccine development and improve protection. Here, we review the clinical prospects of TBV candidates, progress in the development of novel vaccine strategies for TBVs, and the impact of structural vaccinology in TBV design.
Topics: Animals; Anopheles; Antibodies, Monoclonal; Antibodies, Protozoan; Antigens, Protozoan; Humans; Malaria Vaccines; Malaria, Falciparum; Mosquito Vectors; Plasmodium falciparum; Vaccinology
PubMed: 33430656
DOI: 10.1080/14760584.2021.1873135 -
Cell Reports Feb 2021The diversity of circulating human B cells is unknown. We use single-cell RNA sequencing (RNA-seq) to examine the diversity of both antigen-specific and total B cells in...
The diversity of circulating human B cells is unknown. We use single-cell RNA sequencing (RNA-seq) to examine the diversity of both antigen-specific and total B cells in healthy subjects and malaria-exposed individuals. This reveals two B cell lineages: a classical lineage of activated and resting memory B cells and an alternative lineage, which includes previously described atypical B cells. Although atypical B cells have previously been associated with disease states, the alternative lineage is common in healthy controls, as well as malaria-exposed individuals. We further track Plasmodium-specific B cells after malaria vaccination in naive volunteers. We find that alternative lineage cells are primed after the initial immunization and respond to booster doses. However, alternative lineage cells develop an atypical phenotype with repeated boosts. The data highlight that atypical cells are part of a wider alternative lineage of B cells that are a normal component of healthy immune responses.
Topics: Adult; Antibodies, Protozoan; B-Lymphocytes; Child; Child, Preschool; Female; Humans; Malaria; Malaria Vaccines; Male; Plasmodium; RNA-Seq; Vaccination
PubMed: 33567273
DOI: 10.1016/j.celrep.2020.108684 -
Parasites & Vectors Apr 2023Malaria is a vector-borne parasitic disease caused by the apicomplexan protozoan parasite Plasmodium. Malaria is a significant health problem and the leading cause of... (Review)
Review
Malaria is a vector-borne parasitic disease caused by the apicomplexan protozoan parasite Plasmodium. Malaria is a significant health problem and the leading cause of socioeconomic losses in developing countries. WHO approved several antimalarials in the last 2 decades, but the growing resistance against the available drugs has worsened the scenario. Drug resistance and diversity among Plasmodium strains hinder the path of eradicating malaria leading to the use of new technologies and strategies to develop effective vaccines and drugs. A timely and accurate diagnosis is crucial for any disease, including malaria. The available diagnostic methods for malaria include microscopy, RDT, PCR, and non-invasive diagnosis. Recently, there have been several developments in detecting malaria, with improvements leading to achieving an accurate, quick, cost-effective, and non-invasive diagnostic tool for malaria. Several vaccine candidates with new methods and antigens are under investigation and moving forward to be considered for clinical trials. This article concisely reviews basic malaria biology, the parasite's life cycle, approved drugs, vaccine candidates, and available diagnostic approaches. It emphasizes new avenues of therapeutics for malaria.
Topics: Humans; Malaria Vaccines; Malaria; Plasmodium; Antimalarials; Antigens, Protozoan; Malaria, Falciparum; Plasmodium falciparum
PubMed: 37060004
DOI: 10.1186/s13071-023-05755-8 -
Parasitology International Oct 2021An estimated 229 million cases of malaria occurred worldwide in 2019. Both, Plasmodium falciparum and P. vivax are responsible for most of the malaria disease burden in... (Review)
Review
An estimated 229 million cases of malaria occurred worldwide in 2019. Both, Plasmodium falciparum and P. vivax are responsible for most of the malaria disease burden in the world. Despite difficulties in obtaining an accurate number, the global estimates of cases in 2019 are approximately 229 million of which 2.8% are due to P. vivax, and the total number of malaria deaths are approximately 409 million. Regional elimination or global eradication of malaria will be a difficult task, particularly for P. vivax due to the particular biological features related to the hypnozoite, leading to relapse. Countries that have shown successful episodes of a decrease in P. falciparum malaria, are left with remaining P. vivax malaria cases. This is caused by the mechanism that the parasite has evolved to remain dormant in the liver forming hypnozoites. Furthermore, while clinical trials of vaccines against P. falciparum are making fast progress, a very different picture is seen with P. vivax, where only few candidates are currently active in clinical trials. We discuss the challenge that represent the hypnozoite for P. vivax vaccine development, the potential of Controlled Human Malaria Challenges (CHMI) and the leading vaccine candidates assessed in clinical trials.
Topics: Animals; Humans; Malaria Vaccines; Malaria, Vivax; Plasmodium vivax
PubMed: 34166786
DOI: 10.1016/j.parint.2021.102411 -
F1000Research 2020Much of the gain in malaria control, in terms of regional achievements in restricting geographical spread and reducing malaria cases and deaths, can be attributed to... (Review)
Review
Much of the gain in malaria control, in terms of regional achievements in restricting geographical spread and reducing malaria cases and deaths, can be attributed to large-scale deployment of antimalarial drugs, insecticide-treated bed nets, and early diagnostics. However, despite impressive progress, control efforts have stalled because of logistics, unsustainable delivery, or short-term effectiveness of existing interventions or a combination of these reasons. A highly efficacious malaria vaccine as an additional tool would go a long way, but success in the development of this important intervention remains elusive. Moreover, most of the vaccine candidate antigens that were investigated in early-stage clinical trials, selected partly because of their immunogenicity and abundance during natural malaria infection, were polymorphic or structurally complex or both. Likewise, we have a limited understanding of immune mechanisms that confer protection. We reflect on some considerable technological and scientific progress that has been achieved and the lessons learned.
Topics: Antigens, Protozoan; Humans; Malaria; Malaria Vaccines
PubMed: 32399189
DOI: 10.12688/f1000research.22143.1 -
Immunological Reviews Jan 2020Developing efficacious vaccines for human malaria caused by Plasmodium falciparum is a major global health priority, although this has proven to be immensely challenging... (Review)
Review
Developing efficacious vaccines for human malaria caused by Plasmodium falciparum is a major global health priority, although this has proven to be immensely challenging over the decades. One major hindrance is the incomplete understanding of specific immune responses that confer protection against disease and/or infection. While antibodies to play a crucial role in malaria immunity, the functional mechanisms of these antibodies remain unclear as most research has primarily focused on the direct inhibitory or neutralizing activity of antibodies. Recently, there is a growing body of evidence that antibodies can also mediate effector functions through activating the complement system against multiple developmental stages of the parasite life cycle. These antibody-complement interactions can have detrimental consequences to parasite function and viability, and have been significantly associated with protection against clinical malaria in naturally acquired immunity, and emerging findings suggest these mechanisms could contribute to vaccine-induced immunity. In order to develop highly efficacious vaccines, strategies are needed that prioritize the induction of antibodies with enhanced functional activity, including the ability to activate complement. Here we review the role of complement in acquired immunity to malaria, and provide insights into how this knowledge could be used to harness complement in malaria vaccine development.
Topics: Animals; Antibodies, Protozoan; Complement Activation; Complement System Proteins; Disease Models, Animal; Erythrocytes; Host-Parasite Interactions; Humans; Immunity, Innate; Immunization, Passive; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum
PubMed: 31556468
DOI: 10.1111/imr.12802