Malaria Vaccines: Recent Advances and New Horizons

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Term Occurence Count Dictionary
cerebral malaria 1 infectiousdiseases
chloroquine 3 infectiousdiseasesdrugs
hepatitis B 1 infectiousdiseases
malaria 38 infectiousdiseases
meningitis 1 infectiousdiseases
vaccinia 1 infectiousdiseases

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chloroquine 20976 plasmei2 and lisp2) ([107]) is under development.A final WSV strategy delivers wild-type sporozoites under chloroquine drug cover, thus allowing liver-stage parasites to develop fully prior to being killed upon entry into
chloroquine 21165 being killed upon entry into the blood to prevent clinical illness. This approach, initially called “ chloroquine prophylaxis with sporozoites” (CPS), was protective in 100% of volunteers at 8 weeks after final
chloroquine 21846 strain. Use of a specific regimen with non-irradiated, cryopreserved sporozoites delivered by DVI under chloroquine cover (PfSPZ-CVac) has recently shown 100% efficacy (in 9/9 volunteers) against homologous CHMI ([66]),
Select Disease Character Offset Disease Term Instance
cerebral malaria 5630 later this year. According to the World Health Organization (WHO), two safety signals (meningitis, cerebral malaria ) emerged from the Phase III trial, for which the cause is unknown and they noted a confirmed risk of
hepatitis B 4365 comprised of two components: 18 copies of the central repeat and the C-terminal domain of PfCSP fused to hepatitis B virus surface antigen (HBsAg) with extra HBsAg in a 1:4 ratio. RTS,S, formulated with the potent liposomal
malaria 949 date (ppub): 7/2018AbstractThe development of highly effective and durable vaccines against the human malaria parasites Plasmodium falciparum and P. vivax remains a key priority. Decades of endeavor have taught
malaria 1135 of endeavor have taught that achieving this goal will be challenging; however, recent innovation in malaria vaccine research and a diverse pipeline of novel vaccine candidates for clinical assessment provides
malaria 1501 approaches can improve on their success. Here we review the latest vaccine approaches that seek to prevent malaria infection, disease, and transmission and highlight some of the major underlying immunological and molecular
malaria 1935 achieving sustained high-level protection.TeaserDevelopment of highly effective vaccines against human malaria remains a public health priority. In this Review, Draper et al. describe the latest vaccine approaches
malaria 2058 public health priority. In this Review, Draper et al. describe the latest vaccine approaches to prevent malaria alongside immunological and molecular mechanisms of protection. Rational antigen selection, immunogen
malaria 2288 immunization strategies offer promise for achieving high-level protection.Main TextIntroductionModern malaria vaccine development began with seminal studies in mice using irradiated sporozoites ([71]). Although
malaria 3030 efficacy over 2 years against P. falciparum and/or P. vivax (in an era of renewed global interest toward malaria elimination and eradication), while also retaining its original 2015 “landmark” goal of a first-generation
malaria 4028 [70].Sporozoite Subunit VaccinesThe most extensively tested vaccine candidate for prevention of P. falciparum malaria is RTS,S/AS01; this vaccine directs immune responses against the major circumsporozoite protein (PfCSP)
malaria 4606 from GlaxoSmithKline, is the only vaccine that has demonstrated protective efficacy against clinical malaria in a Phase III clinical trial ([86]), although protection is partial, wanes over time, and may be age
malaria 4922 old). In the latter, receiving three vaccinations in a 0-1-2 month schedule, the incidence of clinical malaria was reduced by 51% over the first year of follow-up post-dose three [95% CI 48%–55%]. Over 48 months
malaria 5378 received the three-dose regimen over 7 years, suggests that there may also be a shifting or rebound in malaria incidence 5 years post-vaccination ([73]). Results of a larger long-term follow-up study to the Phase
malaria 5639 this year. According to the World Health Organization (WHO), two safety signals (meningitis, cerebral malaria ) emerged from the Phase III trial, for which the cause is unknown and they noted a confirmed risk of
malaria 6535 overall.One of the most important imperatives for future improvements to RTS,S/AS01, and all next-generation malaria vaccines, is to extend the period of protection, which will require further understanding the mechanisms
malaria 7214 with RTS,S [[75]]) and protection will be tested soon following passive transfer and controlled human malaria infection (CHMI) (Figure 2). RTS,S also contains the C-terminal region of PfCSP; however, the role
malaria 9657 Peak polyclonal anti-NANP serum IgG responses after the final immunization averaged ∼150 μg/mL in malaria -naive adults ([45]), and in the Phase III trial antibody levels declined sharply with initial half-life
malaria 14037 eliciting antibodies with functional activity. Structure-guided vaccine design is just beginning for malaria target antigens, including PfCSP (Figure 3). A detailed molecular picture of protein conformations
malaria 16811 animal models and humans against homologous CHMI, with current studies aiming to define efficacy in malaria -endemic populations, as well as the breadth and duration of protection. WSV rely on administration of
malaria 18532 proportion of participants with any infection from 28 days after the fifth vaccination to the end of the malaria season (20 weeks) was lower in the vaccinated group than in the control group (HR 0.71, 95% CI 0.53–0.92)
malaria 18721 (HR 0.71, 95% CI 0.53–0.92) ([97]). These data suggest that WSV can provide some protection against malaria infection during intense transmission (93% infection rate among placebos). However, a direct comparison
malaria 19430 to the same vaccine regimen in U.S. adults, which may reflect hypo-responsiveness to vaccination in malaria -exposed adults; on-going studies will seek to overcome this obstacle through dose and regimen optimization.
malaria 22441 prevent disease; nevertheless, CPS remains an extremely powerful approach to study highly effective malaria immunity.A major effort in all the aforementioned vaccine studies has been to analyze innate and adaptive
malaria 23280 in vitro, complement-fixing anti-sporozoite IgM ([117]), while passive transfer of purified IgG from malaria -naive US subjects that received the PfSPZ Vaccine and were protected can reduce liver infection >90%
malaria 28559 killing of liver-stage parasites. A recent alternative to emerge has seen the use of P. berghei rodent malaria parasites transgenic for P. falciparum liver-stage antigens of interest. Although an imperfect model,
malaria 29543 the T cells to remain in the liver. These strategies have so far shown promise in mouse models of malaria ([29]), with results of the first Phase Ia trial to assess IV-delivered ChAd63 and MVA ME-TRAP awaited.Blood-Stage
malaria 29712 IV-delivered ChAd63 and MVA ME-TRAP awaited.Blood-Stage VaccinesNaturally acquired immunity (NAI) to malaria arises through repeated exposure to blood-stage parasite diversity, generation of a broad antibody repertoire
malaria 30066 chemically attenuated whole-parasite blood-stage vaccine ([81]) and subunits against pregnancy-associated malaria using VAR2CSA ([79]) have been recently developed that may replicate aspects of NAI, with results awaited.
malaria 30625 vaccine approach given that naturally immune individuals with asymptomatic parasitemia contribute to malaria transmission. In this regard it is particularly encouragingly for the field that new approaches are
malaria 31143 merozoite invasion than routinely achieved by natural exposure. However, this “non-natural” form of malaria immunity could curtail blood-stage parasite carriage, prevent disease, and development of gametocytes,
malaria 31297 carriage, prevent disease, and development of gametocytes, thereby aligning the goals to prevent both malaria disease and transmission.Given that this field has struggled, it is important to consider the challenges
malaria 37946 human efficacy data of PfRH5-based vaccines eagerly awaited.Transmission-Blocking VaccinesUnique among malaria vaccine strategies, those targeting the sexual stages do not directly prevent infection or clinical
malaria 38384 progress and political traction has only happened over the last decade, in line with renewed calls for malaria elimination. Notably, while a transmission-blocking vaccine (TBV) would not directly protect an individual,
malaria 38657 population of asymptomatic and/or submicroscopic carriers, a TBV will serve to arrest onward transmission of malaria and thus provide protection to the community as other vaccines do through herd immunity.The leading
malaria 40628 concentrations (Figure 4). Indeed, defining whether a given level of SMFA activity is sufficient to impact malaria transmission in the field remains an intense area of research ([5], [62]). Importantly, these studies
malaria 43265 delivery technologies for highly immunogenic arrayed antigens bode well for the future testing of defined malaria antigen combinations and improved immunogens.Vaccines for P. vivaxWhile most vaccine development has
malaria 43405 improved immunogens.Vaccines for P. vivaxWhile most vaccine development has focused on the major cause of malaria mortality, P. falciparum, an effective vaccine could also greatly facilitate elimination of P. vivax
malaria 43578 greatly facilitate elimination of P. vivax in many areas of the Americas and Asia-Pacific where standard malaria control tools are facing unique challenges from this parasite’s biology ([68]). These include dormant
malaria 48250 implementation expected to start in late 2018). If successful, this will mark a major milestone in the malaria field. Other vaccines pursuing licensure include PfSPZ Vaccine and R21, although these candidates require
malaria 50275 clinically.Irrespective of life cycle stage, consistent themes and challenges currently pervade the P. falciparum malaria vaccine field. For antibody-inducing strategies, these include the need for more durable and/or functional
meningitis 5618 are expected later this year. According to the World Health Organization (WHO), two safety signals ( meningitis , cerebral malaria) emerged from the Phase III trial, for which the cause is unknown and they noted a
vaccinia 25646 vaccines, especially a chimpanzee adenovirus serotype 63 (ChAd63) prime followed by a boost with modified vaccinia virus Ankara (MVA), have emerged as the most advanced strategy reaching Phase IIb field trials ([28]).

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