Phase 1b Randomized Trial and Follow-Up Study in Uganda of the Blood-Stage Malaria Vaccine Candidate BK-SE36

Palacpac, Nirianne; Ntege, Edward H.; Yeka, Adoke; Balikagala, Betty; Suzuki, Naohiko; Shirai, Hideaki; Yagi, Mamiko; Ito, Kazuya; Fukushima, Wakaba; Hirota, Yoshio; Nsereko, Christopher; Okada, Takuya; Kanoi, Bernard N.; Tetsutani, Kohhei; Arisue, Nobuko; Itagaki, Sawako; Tougan, Takahiro; Ishii, Ken J.; Ueda, Shigeharu; Egwang, Thomas G.; Horii, Toshihiro

doi:10.1371/journal.pone.0064073

Cited by 66 publications

(79 citation statements)

References 30 publications

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“…From 2010 through 2011, a phase 1b clinical trial was conducted in Uganda, followed by a 1-year follow-up study 17) . Local and systemic adverse events were more or less similar to the phase 1a clinical trial, with no volunteers withdrawn due to adverse events ( (Figure-2).…”

Section: Phase 1b In Malaria Immune Ugandan Adults and Young Childrenmentioning

confidence: 99%

Preclinical Studies on a New Vaccine Formulation of BK-SE36, a Malaria Vaccine Candidate

Palacpac

Tougan

Horii

2015

Juntendo Medical Journal

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An effective blood-stage vaccine remains elusive but necessary if we are to reduce malaria morbidity and mortality. The SE36 antigen derived from serine repeat antigen 5 (SERA5) of Plasmodium falciparum remains a promising blood-stage malaria vaccine candidate. The protective efficacy of BK-SE36, SE36 recombinant protein and aluminum hydroxide gel, is continuously being studied in clinical trials. However, the efficacy of BK-SE36 may still be improved with the use of DNA sequences containing CpG motifs that can selectively promote cellular and/or humoral immune responses. Preclinical studies in non-human primates show promising results. A clinical trial of the vaccine candidate BK-SE36/CpG in a malaria-exposed population is awaited as this can give valuable clues on the immune responses towards K3 CpG formulation in malaria-endemic populations.

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Section: Phase 1b In Malaria Immune Ugandan Adults and Young Childrenmentioning

confidence: 99%

Preclinical Studies on a New Vaccine Formulation of BK-SE36, a Malaria Vaccine Candidate

Palacpac

Tougan

Horii

2015

Juntendo Medical Journal

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“…A recent study showed that the 47 kDa fragment bound to host vitronectin, which in turn bound to other host proteins to prevent phagocytosis of merozoites, highlighting a camouflage strategy that facilitates the parasite escape from the host immune response [55]. This phenomena was observed in the Ugandan Phase Ib trial, which reported a linear decrease in the number of vaccine responders with increasing age from 6-10 yearsold, 11-15 years-old, and 16-20 years-old, with only a few vaccine responders observed in the adult cohort (21-35 years-old) [48]. In contrast, 100% seroconversion was reported in a Phase Ia trial with malaria-naive Japanese adults [14].…”

Section: Polymorphism Of Sera Genesmentioning

confidence: 85%

“…5). Notably, an early stage clinical trial and follow-up study in Uganda for the vaccine candidate based on the Pf-SERA5 47 kDa domain, showed that vaccination reduced clinical malaria in the vaccine cohort [48], although assessment of strainspecific response is needed.…”

Section: Polymorphism Of Sera Genesmentioning

confidence: 99%

Characteristic features of the SERA multigene family in the malaria parasite

et al. 2020

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Serine repeat antigen (SERA) is conserved among species of the genus Plasmodium. Sera genes form a multigene family and are generally tandemly clustered on a single chromosome. Although all Plasmodium species encode multiple sera genes, the number varies between species. Among species, the members share similar sequences and gene organization. SERA possess a central papain-like cysteine protease domain, however, in some members, the active site cysteine residue is substituted with a serine. Recent studies implicate this gene family in a number of aspects in parasite biology and induction of protective immune response. This review summarizes the current understanding on this important gene family in several Plasmodium species. The Plasmodium falciparum (Pf)-sera family, for example, consists of nine gene members. Unlike other multigene families in Plasmodium species, Pf-sera genes do not exhibit antigenic variation. Pf-sera5 nucleotide diversity is also low. Moreover, although Pf-sera5 is highly transcribed during the blood stage of malaria infection, and a large amount is released into the host blood following schizont rupture, in malaria endemic countries the sero-positive rates for Pf-SERA5 are low, likely due to Pf-SERA5 binding of host proteins to avoid immune recognition. As an antigen, the N-terminal 47 kDa domain of Pf-SERA5 is a promising vaccine candidate currently undergoing clinical trials. Pf-SERA5 and Pf-SERA6, as well as P. berghei (Pb)-SERA3, and Pb-SERA5, have been investigated for their roles in parasite egress. Two P. yoelii SERA, which have a serine residue at the protease active center, are implicated in parasite virulence. Overall, these studies provide insight that during the evolution of the Plasmodium parasite, the sera gene family members have increased by gene duplication, and acquired various functions that enable the parasite to survive and successfully maintain infection in the host.

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“…Other merozoite protein clinical candidates remaining in the vaccine pipeline from the pre-eradication era are SERA5, MSP3, MSP1, GLURP, AMA1, and EBA-175 (Birkett 2015). Promising early clinical trial data support further investigation into MSP3 (Sirima et al 2011) and SERA5 (Palacpac et al 2013) as possible components in a next-generation malaria vaccine. Another antigen showing preclinical promise is schizont egress antigen-1 (SEA-1).…”

Section: Prevention Of Human -Mosquito Transmission-attacking the Erymentioning

confidence: 92%

Vaccines to Accelerate Malaria Elimination and Eventual Eradication

Healer

Cowman

Kaslow³

et al. 2017

Cold Spring Harb Perspect Med

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Remarkable progress has been made in coordinated malaria control efforts with substantial reductions in malaria-associated deaths and morbidity achieved through mass administration of drugs and vector control measures including distribution of long-lasting insecticideimpregnated bednets and indoor residual spraying. However, emerging resistance poses a significant threat to the sustainability of these interventions. In this light, the malaria research community has been charged with the development of a highly efficacious vaccine to complement existing malaria elimination measures. As the past 40 years of investment in this goal attests, this is no small feat. The malaria parasite is a highly complex organism, exquisitely adapted for survival under hostile conditions within human and mosquito hosts. Here we review current vaccine strategies to accelerate elimination and the potential for novel and innovative approaches to vaccine design through a better understanding of the host-parasite interaction.

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Phase 1b Randomized Trial and Follow-Up Study in Uganda of the Blood-Stage Malaria Vaccine Candidate BK-SE36

Cited by 66 publications

References 30 publications

Preclinical Studies on a New Vaccine Formulation of BK-SE36, a Malaria Vaccine Candidate

Preclinical Studies on a New Vaccine Formulation of BK-SE36, a Malaria Vaccine Candidate

Characteristic features of the SERA multigene family in the malaria parasite

Vaccines to Accelerate Malaria Elimination and Eventual Eradication

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