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NOT Open Access | Malaria vaccine becomes first to achieve 75% efficacy goal in trial of children

April 28, 2021 - 13:46 -- NOT Open Access
Mahase E
BMJ. 2021 Apr 23;373:n1078

A vaccine candidate for malaria has become the first to meet the World Health Organization’s 75% efficacy target, after a trial in 450 children reported 77% efficacy.

NOT Open Access | Inclusion of an Optimized Plasmodium falciparum Merozoite Surface Protein 2-Based Antigen in a Trivalent, Multistage Malaria Vaccine

April 20, 2021 - 15:39 -- NOT Open Access
Eacret JS, Parzych EM, Gonzales DM, Burns JM Jr
J Immunol. 2021 Apr 15;206(8):1817-1831

Plasmodium falciparum merozoite surface protein (PfMSP)2 is a target of parasite-neutralizing Abs. Inclusion of recombinant PfMSP2 (rPfMSP2) as a component of a multivalent malaria vaccine is of interest, but presents challenges. Previously, we used the highly immunogenic PfMSP8 as a carrier to enhance production and/or immunogenicity of malaria vaccine targets. In this study, we exploited the benefits of rPfMSP8 as a carrier to optimize a rPfMSP2-based subunit vaccine. rPfMSP2 and chimeric rPfMSP2/8 vaccines produced in Escherichia coli were evaluated in comparative immunogenicity studies in inbred (CB6F1/J) and outbred (CD1) mice, varying the dose and adjuvant. Immunization of mice with both rPfMSP2-based vaccines elicited high-titer anti-PfMSP2 Abs that recognized the major allelic variants of PfMSP2.

Low immunogenicity of malaria pre-erythrocytic stages can be overcome by vaccination

March 17, 2021 - 09:26 -- Open Access
Müller K, Gibbins MP, Roberts M, Reyes-Sandoval A, Hill AVS, Draper SJ, Matuschewski K, Silvie O, Hafalla JCR
EMBO Mol Med. 2021 Mar 11:e13390

Immunogenicity is considered one important criterion for progression of candidate vaccines to further clinical evaluation. We tested this assumption in an infection and vaccination model for malaria pre-erythrocytic stages. We engineered Plasmodium berghei parasites that harbour a well-characterised epitope for stimulation of CD8+ T cells, either as an antigen in the sporozoite surface-expressed circumsporozoite protein or the parasitophorous vacuole membrane associated protein upregulated in sporozoites 4 (UIS4) expressed in exo-erythrocytic forms (EEFs).

NOT Open Access | Liposome engraftment and antigen combination potentiate the immune response towards conserved epitopes of the malaria vaccine candidate MSP2

February 25, 2021 - 08:17 -- NOT Open Access
Das SC, Price JD, Norton RS, et al.
Vaccine. 2021 Feb 20:S0264-410X(21)00158-4

Merozoite surface protein 2 (MSP2) is a highly abundant, GPI-anchored surface antigen on merozoites of the malaria parasite Plasmodium falciparum. It consists of highly conserved N- and C-terminal domains, and a central polymorphic region that allows all MSP2 alleles to be categorized into the 3D7 or FC27 family. Previously it has been shown that epitope accessibility differs between lipid-bound and lipid-free MSP2, suggesting that lipid interactions modulate the conformation and antigenicity in a way that may better mimic native MSP2 on the merozoite surface.

Natural infections with different Plasmodium species induce antibodies reactive to a chimeric Plasmodium vivax recombinant protein

February 15, 2021 - 15:51 -- Open Access
Jessica N. McCaffery, Balwan Singh, Douglas Nace, Alberto Moreno, Venkatachalam Udhayakumar and Eric Rogier
Malaria Journal 2021 20:86, 12 February 2021

As malaria incidence and transmission in a region decreases, it becomes increasingly difficult to identify areas of active transmission. Improved methods for identifying and monitoring foci of active malaria transmission are needed in areas of low parasite prevalence in order to achieve malaria elimination. Serological assays can provide population-level infection history to inform elimination campaigns.

Two 20-Residue-Long Peptides Derived from Plasmodium vivax Merozoite Surface Protein 10 EGF-Like Domains Are Involved in Binding to Human Reticulocytes

February 11, 2021 - 09:25 -- Open Access
Ricaurte-Contreras LA, Lovera A, Moreno-Pérez DA, Bohórquez MD, Suárez CF, Gutiérrez-Vásquez E, Cuy-Chaparro L, Garzón-Ospina D, Patarroyo MA
Int J Mol Sci. 2021 Feb 5;22(4):1609

Plasmodium parasites' invasion of their target cells is a complex, multi-step process involving many protein-protein interactions. Little is known about how complex the interaction with target cells is in Plasmodium vivax and few surface molecules related to reticulocytes' adhesion have been described to date. Natural selection, functional and structural analysis were carried out on the previously described vaccine candidate P. vivax merozoite surface protein 10 (PvMSP10) for evaluating its role during initial contact with target cells.

Pfs230 yields higher malaria transmission-blocking vaccine activity than Pfs25 in humans but not mice

February 10, 2021 - 10:03 -- Open Access
Healy SA, Anderson CF, Duffy PE, et al.
J Clin Invest. 2021 Feb 9:146221

Vaccines that block human-to-mosquito Plasmodium transmission are needed for malaria eradication and clinical trials have targeted zygote antigen Pfs25 for decades. We reported that a Pfs25 protein-protein conjugate vaccine formulated in alum adjuvant induced significant serum functional activity in both US and Malian adults. However, antibody titers declined rapidly, and transmission-reducing activity required four vaccine doses. Functional immunogenicity and durability must be improved before advancing TBV further in clinical development. We hypothesized that the pre-fertilization protein Pfs230 alone or in combination with Pfs25 would improve functional activity.

NOT Open Access | The challenges of a circumsporozoite protein-based malaria vaccine

February 10, 2021 - 09:33 -- NOT Open Access
Chatterjee D, Cockburn IA
Expert Rev Vaccines. 2021 Feb 7:1-13

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 Plasmodium falciparum circumsporozoite protein (PfCSP) of the malaria parasite. However, protection by RTS,S is incomplete and short-lived.

NOT Open Access | Progress and new horizons toward a VAR2CSA-based placental malaria vaccine

February 8, 2021 - 10:47 -- NOT Open Access
Doritchamou JYA, Suurbaar J, Tuikue Ndam N
Expert Rev Vaccines. 2021 Feb 4:1-12

Several malaria vaccines are under various phases of development with some promising results. In placental malaria (PM) a deliberately anti-disease approach is considered as many studies have underlined the key role of VAR2CSA protein, which therefore represents the leading vaccine candidate. However, evidence indicates that VAR2CSA antigenic polymorphism remains an obstacle to overcome.


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