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The Journal of Clinical Investigation Jan 2022
Review
Topics: Humans; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum
PubMed: 34981788
DOI: 10.1172/JCI156588 -
Science Translational Medicine Nov 2022The RTS,S vaccine has recently been recommended for implementation as a childhood vaccine in regions with moderate-to-high malaria transmission. We discuss mechanisms of... (Review)
Review
The RTS,S vaccine has recently been recommended for implementation as a childhood vaccine in regions with moderate-to-high malaria transmission. We discuss mechanisms of vaccine protection and longevity, implementation considerations, and future research needed to increase the vaccine's health impact, including vaccine modifications for higher efficacy and longevity of protection.
Topics: Humans; Infant; Child; Malaria Vaccines; Malaria; Malaria, Falciparum; Plasmodium falciparum
PubMed: 36383682
DOI: 10.1126/scitranslmed.abo6646 -
The Lancet. Infectious Diseases Aug 2023In October, 2021, WHO recommended that the RTS,S malaria vaccine, with its strong safety profile and high impact, be provided to children from age 5 months in regions... (Review)
Review
In October, 2021, WHO recommended that the RTS,S malaria vaccine, with its strong safety profile and high impact, be provided to children from age 5 months in regions with moderate to high Plasmodium falciparum malaria transmission. The evidence base included phase 3 trials in seven African countries and an ongoing malaria vaccine implementation programme (MVIP) in three African countries. We highlight problems with the MVIP mortality data, including potential confounding, inappropriate use of severe malaria as a surrogate marker, a statistically non-significant effect, and assessment after 2 years instead of the stipulated 4 years, which could have inflated the benefits and deflated the risks associated with the vaccine. We conclude that the claimed impact of the MVIP on mortality is not based on enough scientific evidence and that the MVIP findings do not rule out the possibility of increased mortality among vaccinated girls compared with vaccinated boys, as observed in the phase 3 studies. The MVIP should adhere fully to the planned analyses and the data should be made available for independent assessment. Roll-out of the vaccine elsewhere should include rigorous evaluation, especially of its safety.
Topics: Female; Humans; Infant; Male; Africa; Malaria; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum; Child, Preschool
PubMed: 37086747
DOI: 10.1016/S1473-3099(23)00126-3 -
Expert Review of Vaccines Feb 2021: An effective vaccine against malaria forms a global health priority. Both naturally acquired immunity and sterile protection induced by irradiated sporozoite... (Review)
Review
: An effective vaccine against malaria forms a global health priority. Both naturally acquired immunity and sterile protection induced by irradiated sporozoite immunization were described decades ago. Still no vaccine exists that sufficiently protects children in endemic areas. Identifying immunological correlates of vaccine efficacy can inform rational vaccine design and potentially accelerate clinical development.: We discuss recent research on immunological correlates of malaria vaccine efficacy, including: insights from state-of-the-art omics platforms and systems vaccinology analyses; functional anti-parasitic assays; pre-immunization predictors of vaccine efficacy; and comparison of correlates of vaccine efficacy against controlled human malaria infections (CHMI) and against naturally acquired infections.: Effective vaccination may be achievable without necessarily understanding immunological correlates, but the relatively disappointing efficacy of malaria vaccine candidates in target populations is concerning. Hypothesis-generating omics and systems vaccinology analyses, alongside assessment of pre-immunization correlates, have the potential to bring about paradigm-shifts in malaria vaccinology. Functional assays may represent effector mechanisms, but have scarcely been formally assessed as correlates. Crucially, evidence is still meager that correlates of vaccine efficacy against CHMI correspond with those against naturally acquired infections in target populations. Finally, the diversity of immunological assays and efficacy endpoints across malaria vaccine trials remains a major confounder.
Topics: Animals; Child; Humans; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum; Sporozoites; Vaccination; Vaccinology
PubMed: 33499692
DOI: 10.1080/14760584.2021.1882309 -
Nature Microbiology Nov 2021A promising vaccine fails to provide durable protection against infection and clinical malaria in infants, a key malaria vaccine target population, in a phase 2b...
A promising vaccine fails to provide durable protection against infection and clinical malaria in infants, a key malaria vaccine target population, in a phase 2b clinical trial. The need for a highly effective vaccine against malaria remains as urgent as ever.
Topics: Malaria Vaccines
PubMed: 34635830
DOI: 10.1038/s41564-021-00982-0 -
Annual Review of Microbiology Sep 2018Malaria vaccine development has rapidly advanced in the past decade. The very first phase 3 clinical trial of the RTS,S vaccine was completed with over 15,000 African... (Review)
Review
Malaria vaccine development has rapidly advanced in the past decade. The very first phase 3 clinical trial of the RTS,S vaccine was completed with over 15,000 African infants and children, and pilot implementation studies are underway. Next-generation candidate vaccines using novel antigens, platforms, or approaches targeting different and/or multiple stages of the Plasmodium life cycle are being tested. Many candidates, in various stages of development, promise enhanced efficacy of long duration and broad protection against genetically diverse malaria strains, with a few studies under way in target populations in endemic areas. Malaria vaccines together with other interventions promise interruption and eventual elimination of malaria in endemic areas.
Topics: Clinical Trials, Phase III as Topic; Drug Discovery; Drug Evaluation, Preclinical; Humans; Malaria; Malaria Vaccines; Plasmodium
PubMed: 30200856
DOI: 10.1146/annurev-micro-090817-062427 -
Expert Review of Vaccines Feb 2021A safe and effective vaccine will likely be necessary for the control or eradication of malaria which kills 400,000 annually. Our most advanced vaccine candidate to date... (Review)
Review
INTRODUCTION
A safe and effective vaccine will likely be necessary for the control or eradication of malaria which kills 400,000 annually. Our most advanced vaccine candidate to date is RTS,S which is based on the circumsporozoite protein (PfCSP) of the malaria parasite. However, protection by RTS,S is incomplete and short-lived.
AREAS COVERED
Here we summarize results from recent clinical trials of RTS,S and critically evaluate recent studies that aim to understand the correlates of protective immunity and why vaccine-induced protection is short-lived. In particular, recent systems serology studies have highlighted a key role for the necessity of inducing functional antibodies. In-depth analyses of immune responses to CSP in both mouse models and vaccinated humans have also highlighted difficulties in generating the maintaining high-quality antibody responses. Finally, in recent years biophysical and structural studies of antibody binding to PfCSP have led to a better understanding of how highly potent antibodies can block infection, which can inform vaccine design.
EXPERT OPINION
We highlight how both structure-guided vaccine design and a better understanding of the immune response to PfCSP can inform a second generation of PfCSP-based vaccines stimulating a broader range of protective targets within PfCSP.
Topics: Animals; Antibodies, Protozoan; Humans; Malaria Vaccines; Malaria, Falciparum; Mice; Plasmodium falciparum; Protozoan Proteins; Time Factors
PubMed: 33554669
DOI: 10.1080/14760584.2021.1874924 -
Frontiers in Immunology 2018The quest for a licensed effective vaccine against malaria remains a global priority. Even though classical vaccine design strategies have been successful for some viral... (Review)
Review
The quest for a licensed effective vaccine against malaria remains a global priority. Even though classical vaccine design strategies have been successful for some viral and bacterial pathogens, little success has been achieved for , which causes the deadliest form of malaria due to its diversity and ability to evade host immune responses. Nevertheless, recent advances in vaccinology through high throughput discovery of immune correlates of protection, lymphocyte repertoire sequencing and structural design of immunogens, provide a comprehensive approach to identifying and designing a highly efficacious vaccine for malaria. In this review, we discuss novel vaccine approaches that can be employed in malaria vaccine design.
Topics: Animals; Humans; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum
PubMed: 30555463
DOI: 10.3389/fimmu.2018.02769 -
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 -
Lancet (London, England) Jan 2004Large gains in the reduction of malaria mortality in the early 20th century were lost in subsequent decades. Malaria now kills 2-3 million people yearly. Implementation... (Review)
Review
Large gains in the reduction of malaria mortality in the early 20th century were lost in subsequent decades. Malaria now kills 2-3 million people yearly. Implementation of malaria control technologies such as insecticide-treated bednets and chemotherapy could reduce mortality substantially, but an effective malaria vaccine is also needed. Advances in vaccine technology and immunology are being used to develop malaria subunit vaccines. Novel approaches that might yield effective vaccines for other diseases are being evaluated first in malaria. We describe progress in malaria vaccine development in the past 5 years: reasons for cautious optimism, the type of vaccine that might realistically be expected, and how the process could be hastened. Although exact predictions are not possible, if sufficient funding were mobilised, a deployable, effective malaria vaccine is a realistic medium-term to long-term goal.
Topics: Animals; Antibody Formation; Antigens, Protozoan; Humans; Malaria; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum; Vaccination
PubMed: 14726170
DOI: 10.1016/S0140-6736(03)15267-1