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Combining malaria vaccination with chemoprevention: a promising new approach to malaria control

September 8, 2021 - 16:21 -- Open Access
Brian Greenwood, Matthew Cairns, Mike Chaponda, R. Matthew Chico, Alassane Dicko, Jean-Bosco Ouedraogo, Kamija S. Phiri, Feiko O. ter Kuile and Daniel Chandramohan
Malaria Journal 2021 20:361, 6 September 2021

Malaria control has stalled in a number of African countries and novel approaches to malaria control are needed for these areas. The encouraging results of a recent trial conducted in young children in Burkina Faso and Mali in which a combination of the RTS,S/AS01E malaria vaccine and seasonal malaria chemoprevention led to a substantial reduction in clinical cases of malaria, severe malaria, and malaria deaths compared with the administration of either intervention given alone suggests that there may be other epidemiological/clinical situations in which a combination of malaria vaccination and chemoprevention could be beneficial.

NOT Open Access | Harnessing liver-resident memory T cells for protection against malaria

January 31, 2021 - 15:51 -- NOT Open Access
Fernandez-Ruiz D, de Menezes MN, Holz LE, Ghilas S, Heath WR, Beattie L
Expert Rev Vaccines. 2021 Jan 27

Tissue-resident memory T cells (TRM cells) are powerful mediators of protracted adaptive immunity to infection in peripheral organs. Harnessing TRM cells through vaccination hence promises unprecedented potential for protection against infection. A paramount example of this is malaria, a major infectious disease for which immunity through traditional vaccination strategies remains challenging. Liver TRM cells appear to be highly protective against malaria, and recent developments in our knowledge of the biology of these cells have defined promising, novel strategies for their induction.

Protective Vaccination Reshapes Hepatic Response to Blood-Stage Malaria of Genes Preferentially Expressed by NK Cells

November 19, 2020 - 13:13 -- Open Access
Araúzo-Bravo MJ, Delic D, Gerovska D, Wunderlich F
Vaccines (Basel). 2020 Nov 13;8(4):E677

The role of natural killer (NK) cells in the liver as first-line post infectionem (p.i.) effectors against blood-stage malaria and their responsiveness to protective vaccination is poorly understood. Here, we investigate the effect of vaccination on NK cell-associated genes induced in the liver by blood-stage malaria of Plasmodium chabaudi. Female Balb/c mice were vaccinated at weeks 3 and 1 before being infected with 106P. chabaudi-parasitized erythrocytes.

Antibody Feedback Limits the Expansion of B Cell Responses to Malaria Vaccination but Drives Diversification of the Humoral Response

October 15, 2020 - 08:50 -- Open Access
McNamara HA, Idris AH, Cockburn IA, et al.
Cell Host Microbe. 2020 Oct 7;28(4):572-585.e7

Generating sufficient antibody to block infection is a key challenge for vaccines against malaria. Here, we show that antibody titers to a key target, the repeat region of the Plasmodium falciparum circumsporozoite protein (PfCSP), plateaued after two immunizations in a clinical trial of the radiation-attenuated sporozoite vaccine. To understand the mechanisms limiting vaccine responsiveness, we developed immunoglobulin (Ig)-knockin mice with elevated numbers of PfCSP-binding B cells.

Seasonal malaria vaccination: protocol of a phase 3 trial of seasonal vaccination with the RTS,S/AS01(E) vaccine, seasonal malaria chemoprevention and the combination of vaccination and chemoprevention

September 16, 2020 - 13:13 -- Open Access
Chandramohan D, Dicko A, Greenwood B, et al.
BMJ Open. 2020 Sep 15;10(9):e035433

Seasonal malaria chemoprevention (SMC), with sulphadoxine-pyrimethamine plus amodiaquine (SP+AQ) is effective but does not provide complete protection against clinical malaria. The RTS,S/AS01E malaria vaccine provides a high level of protection shortly after vaccination, but this wanes rapidly. Such a vaccine could be an alternative or additive to SMC. This trial aims to determine whether seasonal vaccination with RTS,S/AS01E vaccine could be an alternative to SMC and whether a combination of the two interventions would provide added benefits.

Comparison of ELISA with electro-chemiluminescence technology for the qualitative and quantitative assessment of serological responses to vaccination

April 20, 2020 - 09:47 -- Open Access
Jessica S. Bolton, Sidhartha Chaudhury, Sheetij Dutta, Scott Gregory, Emily Locke, Tony Pierson and Elke S. Bergmann-Leitner
Malaria Journal 2020 19:159, 17 April 2020

Profiling immune responses induced by either infection or vaccination can provide insight into identification of correlates of protection. Furthermore, profiling of serological responses can be used to identify biomarkers indicative of exposure to pathogens. Conducting such immune surveillance requires readout methods that are high-throughput, robust, and require small sample volumes. While the enzyme-linked immunosorbent assay (ELISA) is the classical readout method for assessing serological responses, the advent of multiplex assays has significantly increased the throughput and capacity for immunoprofiling. This report describes the development and assay performance (sensitivity, linearity of detection, requirement for multiple dilutions for each sample, intra- and inter-assay variability) of an electro-chemiluminescence (ECLIA)-based multiplex assay.

Microarray analyses reveal strain-specific antibody responses to Plasmodium falciparum apical membrane antigen 1 variants following natural infection and vaccination

March 9, 2020 - 15:03 -- Open Access
Bailey JA, Berry AA, Plowe CV, et al.
Sci Rep. 2020 Mar 3;10(1):3952

Vaccines based on Plasmodium falciparum apical membrane antigen 1 (AMA1) have failed due to extensive polymorphism in AMA1. To assess the strain-specificity of antibody responses to malaria infection and AMA1 vaccination, we designed protein and peptide microarrays representing hundreds of unique AMA1 variants. Following clinical malaria episodes, children had short-lived, sequence-independent increases in average whole-protein seroreactivity, as well as strain-specific responses to peptides representing diverse epitopes.

Vaccination with virosomally formulated recombinant CyRPA elicits protective antibodies against Plasmodium falciparum parasites in preclinical in vitro and in vivo models

February 11, 2020 - 16:23 -- Open Access
Marco Tamborrini, Julia Hauser, Anja Schäfer, Mario Amacker, Paola Favuzza, Kwak Kyungtak, Sylvain Fleury, Gerd Pluschke
NPJ Vaccines. 2020; 5:9

The Plasmodium falciparum (Pf) cysteine-rich protective antigen (PfCyRPA) has emerged as a promising blood-stage candidate antigen for inclusion into a broadly cross-reactive malaria vaccine. This highly conserved protein among various geographical strains plays a key role in the red blood cell invasion process by P. falciparum merozoites, and antibodies against PfCyRPA can efficiently prevent the entry of the malaria parasites into red blood cells.

Vaccination accelerates hepatic erythroblastosis induced by blood-stage malaria

February 3, 2020 - 17:05 -- Open Access
Denis Delic, Frank Wunderlich, Saleh Al-Quraishy, Abdel-Azeem S. Abdel-Baki, Mohamed A. Dkhil and Marcos J. Araúzo-Bravo
Malaria Journal 2020 19:49, 29 January 2020

Vaccination induces survival of otherwise lethal blood-stage infections of the experimental malaria Plasmodium chabaudi. Blood-stage malaria induces extramedullary erythropoiesis in the liver. This study investigates how vaccination affects the course of malaria-induced expression of erythrocytic genes in the liver.

The Costs of Implementing Vaccination With the RTS,S Malaria Vaccine in Five Sub-Saharan African Countries

January 14, 2020 - 16:32 -- Open Access
Sicuri E, Yaya Bocoum F, Nonvignon J, Alonso S, Fakih B, Bonsu G, Kariuki S, Leeuwenkamp O, Munguambe K, Mrisho M, Were V, Sauboin C
MDM Policy & Practice, 2019 Dec 19;4(2):2381468319896280

The World Health Organization has recommended pilot implementation of a candidate vaccine against malaria (RTS,S/AS01) in selected sub-Saharan African countries. This exploratory study aimed to estimate the costs of implementing RTS,S in Burkina Faso, Ghana, Kenya, Mozambique, and Tanzania.


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