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In silico identification of novel open reading frames in Plasmodium falciparum oocyte and salivary gland sporozoites using proteogenomics framework

February 8, 2021 - 10:50 -- Open Access
Sophie Gunnarsson and Sudhakaran Prabakaran
Malaria Journal 2021 20:71, 5 February 2021

Plasmodium falciparum causes the deadliest form of malaria, which remains one of the most prevalent infectious diseases. Unfortunately, the only licensed vaccine showed limited protection and resistance to anti-malarial drug is increasing, which can be largely attributed to the biological complexity of the parasite’s life cycle. The progression from one developmental stage to another in P. falciparum involves drastic changes in gene expressions, where its infectivity to human hosts varies greatly depending on the stage. Approaches to identify candidate genes that are responsible for the development of infectivity to human hosts typically involve differential gene expression analysis between stages. However, the detection may be limited to annotated proteins and open reading frames (ORFs) predicted using restrictive criteria.

NOT Open Access | Correlates of malaria vaccine efficacy

January 27, 2021 - 15:39 -- NOT Open Access
Stanisic DI, McCall MBB
Expert Rev Vaccines. 2021 Jan 27

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.

Role of human Pegivirus infections in whole Plasmodium falciparum sporozoite vaccination and controlled human malaria infection in African volunteers

January 27, 2021 - 15:30 -- Open Access
Tumbo AM, Schindler T, Daubenberger C, et al.
Virol J. 2021 Jan 26;18(1):28

Diverse vaccination outcomes and protection levels among different populations pose a serious challenge to the development of an effective malaria vaccine. Co-infections are among many factors associated with immune dysfunction and sub-optimal vaccination outcomes. Chronic, asymptomatic viral infections can contribute to the modulation of vaccine efficacy through various mechanisms. Human Pegivirus-1 (HPgV-1) persists in immune cells thereby potentially modulating immune responses. We investigated whether Pegivirus infection influences vaccine-induced responses and protection in African volunteers undergoing whole P. falciparum sporozoites-based malaria vaccination and controlled human malaria infections (CHMI).

NOT Open Access | Development of Plasmodium-specific liver resident-memory CD8(+) T cells after heat-killed sporozoite immunization in mice

January 27, 2021 - 10:03 -- NOT Open Access
Ghilas S, Enders MH, May R, Holz L, Fernandez-Ruiz D, Cozijnsen A, Mollard V, Cockburn IA, McFadden GI, Heath WR, Beattie L
Eur J Immunol. 2021 Jan 23

Malaria remains a major cause of mortality in the world, and an efficient vaccine is the best chance of reducing the disease burden. Vaccination strategies for the liver stage of disease that utilise injection of living radiation-attenuated sporozoites (RAS) confer sterile immunity, which is mediated by CD8+ memory T cells, with liver-resident memory T cells (TRM ) being particularly important. We have previously described a TCR transgenic mouse, termed PbT-I, where all CD8+ T cells recognize a specific peptide from Plasmodium. PbT-I form liver TRM cells upon RAS injection and are capable of protecting mice against challenge infection.

A chemokine-fusion vaccine targeting immature dendritic cells elicits elevated antibody responses to malaria sporozoites in infant macaques

January 21, 2021 - 15:21 -- Open Access
Luo K, Gordy JT, Zavala F, Markham RB
Sci Rep. 2021 Jan 13;11(1):1220

Infants and young children are the groups at greatest risk for severe disease resulting from Plasmodium falciparum infection. We previously demonstrated in mice that a protein vaccine composed of the chemokine macrophage inflammatory protein 3α genetically fused to the minimally truncated circumsporozoite protein of P. falciparum (MCSP) elicits high concentrations of specific antibody and significant reduction of liver sporozoite load in a mouse model system.

NOT Open Access | A mosquito salivary protein facilitates sporozoite traversal of host cells

December 15, 2020 - 14:12 -- NOT Open Access
Chuang YM, Agunbiade TA, Tang XD, Freudzon M, Almeras L, Fikrig E
J Infect Dis. 2020 Dec 11:jiaa759

Malaria begins when Plasmodium-infected Anopheles mosquitoes take a blood meal on a vertebrate. During the initial probing process, mosquitoes inject saliva and sporozoites into the host skin. Components of mosquito saliva have the potential to influence sporozoite functionality. Sporozoite-associated mosquito saliva protein 1 (SAMSP1, AGAP013726) was among several proteins identified when sporozoites were isolated from saliva, suggesting it may have an effect on Plasmodium. Recombinant SAMSP1 enhanced sporozoite gliding and cell traversal activity in vitro.

NOT Open Access | Dynamics of blood stage and sporozoite-induced malarial infections in experimentally infected passerines

September 8, 2020 - 11:44 -- NOT Open Access
Palinauskas V, Platonova E, Žiegytė R, Mukhin A
Int J Parasitol. 2020 Aug 31:S0020-7519(20)30248-4

Complex experimental studies of vertebrate host, vector, and parasite interactions are essential in understanding virulence, but are difficult or impossible to conduct if vector species are unknown. Subinoculation of erythrocytic meronts of avian malarial parasites into susceptible hosts can avoid this problem, but this approach omits early exoerythrocytic stages, e.g. cryptozoites and metacryptozoites, that normally develop from sporozoites.

Molecular determinants of SR-B1-dependent Plasmodium sporozoite entry into hepatocytes

August 13, 2020 - 11:43 -- Open Access
Langlois AC, Manzoni G, Vincensini L, Coppée R, Marinach C, Guérin M, Huby T, Carrière V, Cosset FL, Dreux M, Rubinstein E, Silvie O
Sci Rep. 2020 Aug 11;10(1):13509

Sporozoite forms of the Plasmodium parasite, the causative agent of malaria, are transmitted by mosquitoes and first infect the liver for an initial round of replication before parasite proliferation in the blood. The molecular mechanisms involved during sporozoite invasion of hepatocytes remain poorly understood. Two receptors of the Hepatitis C virus (HCV), the tetraspanin CD81 and the scavenger receptor class B type 1 (SR-B1), play an important role during the entry of Plasmodium sporozoites into hepatocytes.

Transcriptomics and proteomics reveal two waves of translational repression during the maturation of malaria parasite sporozoites

November 7, 2019 - 21:20 -- Open Access
Lindner SE, Swearingen KE, Shears MJ, Walker MP, Vrana EN, Hart KJ, Minns AM, Sinnis P, Moritz RL, Kappe SHI
Nat Commun. 2019 Oct 31;10(1):4964

Plasmodium sporozoites are transmitted from infected mosquitoes to mammals, and must navigate the host skin and vasculature to infect the liver. This journey requires distinct proteomes.

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