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Clustering and Erratic Movement Patterns of Syringe-Injected versus Mosquito-Inoculated Malaria Sporozoites Underlie Decreased Infectivity

April 14, 2021 - 16:29 -- Open Access
de Korne CM, Winkel BMF, Roestenberg M, et al.
mSphere. 2021 Apr 7;6(2):e00218-21

Malaria vaccine candidates based on live, attenuated sporozoites have led to high levels of protection. However, their efficacy critically depends on the sporozoites' ability to reach and infect the host liver. Administration via mosquito inoculation is by far the most potent method for inducing immunity but highly impractical. Here, we observed that intradermal syringe-injected Plasmodium berghei sporozoites (syrSPZ) were 3-fold less efficient in migrating to and infecting mouse liver than mosquito-inoculated sporozoites (msqSPZ).

Transcriptional heterogeneity and tightly regulated changes in gene expression during Plasmodium berghei sporozoite development

March 10, 2021 - 13:20 -- Open Access
Bogale HN, Pascini TV, Kanatani S, Sá JM, Wellems TE, Sinnis P, Vega-Rodríguez J, Serre D
Proc Natl Acad Sci U S A. 2021 Mar 9;118(10):e2023438118

Despite the critical role of Plasmodium sporozoites in malaria transmission, we still know little about the mechanisms underlying their development in mosquitoes. Here, we use single-cell RNA sequencing to characterize the gene expression profiles of 16,038 Plasmodium berghei sporozoites isolated throughout their development from midgut oocysts to salivary glands, and from forced salivation experiments.

A New Test of a Theory about Old Mosquitoes

March 3, 2021 - 16:42 -- Open Access
Smith DL, Musiime AK, Maxwell K, Lindsay SW, Kiware S
Trends Parasitol. 2021 Mar;37(3):185-194

In vector control, it is widely accepted that killing adult mosquitoes would sharply reduce the proportion of old mosquitoes and cause the greatest changes to malaria transmission. The principle is based on a mathematical model of the sporozoite rate (the proportion of infective mosquitoes) that emphasized changes in mosquito age.

Single-cell RNA sequencing reveals developmental heterogeneity among Plasmodium berghei sporozoites

February 25, 2021 - 09:49 -- Open Access
Ruberto AA, Bourke C, Merienne N, Obadia T, Amino R, Mueller I
Sci Rep. 2021 Feb 22;11(1):4127

In the malaria-causing parasite's life cycle, Plasmodium sporozoites must travel from the midgut of a mosquito to the salivary glands before they can infect a mammalian host. However, only a fraction of sporozoites complete the journey. Since salivary gland invasion is required for transmission of sporozoites, insights at the molecular level can contribute to strategies for malaria prevention.

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.


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