Optimizing a deployable high efficacy malaria vaccine

Informations projet

OptiMalVax

N° de convention de subvention: 733273

DOI

10.3030/733273

Projet clôturé

Date de signature de la CE 9 Decembre 2016

Date de début 1 Janvier 2017

Date de fin 31 Decembre 2022

Financé au titre de

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Coût total

€ 23 741 228,75

Contribution de l’UE

€ 20 050 441,25

Coordonné par

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom

CORDIS fournit des liens vers les livrables publics et les publications des projets HORIZON.

Les liens vers les livrables et les publications des projets du 7e PC, ainsi que les liens vers certains types de résultats spécifiques tels que les jeux de données et les logiciels, sont récupérés dynamiquement sur OpenAIRE .

Livrables

Documents, reports (34)

4.3 Generate VLPs for two TBV candidates and assess immunogenicity/TB

Generate VLPs for two TBV candidates and assess immunogenicity and TB activity

6.4 Preclinical studies completed for adjuvant

Preclinical studies completed for adjuvant

7.5 Report on safety and immunogenicity of vectored prime-target immunisation in healthy volunteers

Report on safety and immunogenicity of vectored prime-target immunisation in healthy volunteers

1.5 Generation of 8 transgenic P berghei parasites expressing novel P falciparum antigens

Creation of 8 transgenic P. berghei parasites expressing novel P. falciparum sporozoite antigens

10.2 Establish relevant committees including PSC, PMMC, ISAC

Report on the establishment of relevant committees including the Project Steering Committee and a Project Management and Monitoring Committee, and ISAC

2.1 Liver-stage antigens identified from HLA molecules of parasitized hepatocytes

Report on the nature of liver-stage antigens identified by sequencing of eluted peptides from the HLA molecules of parasitized hepatocytes

5.2 Adequate process for lead novel VLPs for initial GMP production

Adequate process for lead novel VLPs for initial (Phase I trial scale) GMP production

2.3 Rank ordering of the protective efficacy of new liver-stage antigen candidates

Rank ordering of the protective efficacy of new liverstage antigen candidates assessed in in vivo murine models using transgenic parasite challenge

5.1 generation of five new VLPs with SnoopCatcher and SpyCatcher

Report on generation of five new VLPs with SnoopCatcher and SpyCatcher and on the relative robustness of each platform for displaying multiple antigens

1.4 Generation of 8 new vectored vaccine candidates

Generation of 8 new vectored vaccine candidates expressing the 8 elected antigens of deliverable 1.1.

1.3 Generation of lead bivalent sporozoite VLP suitable for progression to GMP

Generation of lead bivalent sporozoite VLP suitable for progression to GMP biomanufacture

4.1 Identification of new novel candidates from natural blockers and proteomic screen

Identification of new novel candidates from natural blockers and proteomic screen

4.5 Assess immunogenicity and TBA of bivalent VLPs to select candidate for GMP manufacture

Assess immunogenicity and TBA of bivalent VLPs to select candidate for GMP manufacture

3.4 Efficacy of new candidate blood-stage antigens

Report on efficacy of new candidate bloodstage antigens

3.1 Preferred VLP for generation of bi-valent blood-stage immunogen

Report on preferred VLP for generation of a bi-valent blood-stage immunogen

3.2 Immunogenicity and growth inhibitory activity of the lead blood-stage bivalent VLP

Report on the immunogenicity and growth inhibitory activity of the lead blood-stage bivalent VLP

5.3 Comparison of immunogenicity of lead VLPs and evidence of non-interference

Comparison of immunogenicity of the VLPs generated with identification of the lead VLPs and evidence of non-interference between lead sporozoite-, blood-stage and transmission-stage VLPs

7.7 Report on safety and immunogenicity of R21b in matrix M adjuvant

Report on safety and immunogenicity of R21b in matrix M adjuvant

2.4 Utility of new prime-target immunisation approaches in liver-stage protective immunity in mice

Report of the utility of new primetarget immunisation approaches in generating durable liverstage protective immunity in mice

1.6 Efficacy data on new antigens allowing rank ordering

Efficacy data on new sporozoite antigens allowing rank ordering of protective efficacy of lead antigens

8.4 Report on safety and immunogenicity of blood-stage VLP/vaccine

Report on safety and immunogenicity of bloodstage VLPvaccine in clinical trial

10.8 List of publications

List of publications arising from project including any at manuscript preparation stage as some data may not be published until after the end date of the project

4.2 Validation of selected novel candidate and comparison with leading antigens

Validation of selected novel candidate and comparison with leading antigens

7.6 Report on efficacy against sporozoite challenge of prime-target immunisation in healthy volunteers

Report on efficacy against sporozoite challenge of prime-target immunisation in healthy volunteers

3.3 Structural studies of PfRH5 pathway components

Report on structural studies of PfRH5 pathway components

9.5 TB activity of TBV candidates

Transmission Blocking activity of TBV candidates

5.4 Optimised process for biomanufacture of lead novel VLPs for GMP production

Optimised process for biomanufacture of lead novel VLPs for high yield larger scale GMP production

2.2 Ability of specific liver-stage antigen expression in hepatocytes to be detected by using marker epitopes

Report on the ability of specific liver-stage antigen expression in hepatocytes to be detected by using marker epitopes inserted into P. falciparum liver-stage antigens by CRISPR/Cas9 technology

4.4 Generate VLPs expressing Pfs25 alone, Pfs48/45 alone and bivalent VLPs

Generate VLPs expressing Pfs25 alone, Pfs48/45 alone and bivalent VLPs

8.5 Report on immuno-efficacy of blood-stage VLP/vaccine

Report on immunoefficacy of bloodstage VLPvaccine in clinical trial

1.2 Definition of 8 selected new candidate sporozoite antigens

Definition of 8 selected new candidate sporozoite antigens based on invasion analysis, proteomics and immunoepidemiology

9.4 Safety and Immunogenicity of TBV candidates

Safety and Immunogenicity of TBV candidates

7.8 Report on efficacy against sporozoite challenge of vectored prime-target immunisation combined with R21b in healthy volunteers

Report on efficacy against sporozoite challenge of vectored primetarget immunisation combined with R21b in healthy volunteers

5.5 feasibility of enhancing the durability of protective immune responses using VLPs in microcapsules

Report on the feasibility of enhancing the durability of protective immune responses using VLPs in microcapsules

Websites, patent fillings, videos etc. (1)

10.1 Creation of website

Successful creation of project website

Publications

Peer reviewed articles (15)

Heterologous Expression and Evaluation of Novel Plasmodium falciparum Transmission Blocking Vaccine Candidates

Auteurs: Roos M. de Jong, Susheel K. Singh, Karina Teelen, Marga van de Vegte-Bolmer, Geert-Jan van Gemert, Will J. R. Stone, Emily Locke, Jordan Plieskatt, Michael Theisen, Teun Bousema, Matthijs M. Jore
Publié dans: Frontiers in Immunology, 2022, ISSN 1664-3224
Éditeur: Frontiers Media SA
DOI: 10.3389/fimmu.2022.909060

Screening of viral-vectored P. falciparum pre-erythrocytic candidate vaccine antigens using chimeric rodent parasites

Auteurs: Surendra Kumar Kolli, Ahmed M. Salman, Jai Ramesar, Severine Chevalley-Maurel, Hans Kroeze, Fiona G. A. Geurten, Shinya Miyazaki, Ekta Mukhopadhyay, Catherin Marin-Mogollon, Blandine Franke-Fayard, Adrian V. S. Hill, Chris J. Janse
Publié dans: PLOS ONE, Numéro 16/7, 2021, Page(s) e0254498, ISSN 1932-6203
Éditeur: Public Library of Science
DOI: 10.1371/journal.pone.0254498

Preclinical development of a Pfs230-Pfs48/45 chimeric malaria transmission-blocking vaccine

Auteurs: Susheel K. Singh1,2, Jordan Plieskatt3, Bishwanath K. Chourasia1,2, Vandana Singh1,2, Karin Lövgren Bengtsson4, Jenny M. Reimer 4, Renate C. van Daalen5, Karina Teelen5, Marga van de Vegte-Bolmer5, Geert-Jan van Gemert5, Matthijs M. Jore 5,6✉ and Michael Theisen
Publié dans: NPJ Vaccines, 2021, ISSN 2059-0105
Éditeur: Springer Nature
DOI: 10.1038/s41541-021-00383-8

Structure of the malaria vaccine candidate Pfs48/45 and its recognition by transmission blocking antibodies

Auteurs: Ko KT, Lennartz F, Mekhaiel D, Guloglu B, Marini A, Deuker DJ, Long CA, Jore MM, Miura K, Biswas S, Higgins MK
Publié dans: Nature Communications, 2022, ISSN 2041-1723
Éditeur: Nature Publishing Group
DOI: 10.1038/s41467-022-33379-6

A Reproducible and Scalable Process for Manufacturing a Pfs48/45 Based Plasmodium falciparum Transmission-Blocking Vaccine

Auteurs: Susheel K. Singh, Jordan Plieskatt, Bishwanath K. Chourasia, Amanda Fabra-García, Asier Garcia-Senosiain, Vandana Singh, Karin Lövgren Bengtsson, Jenny M. Reimer, Robert Sauerwein, Matthijs M. Jore, Michael Theisen
Publié dans: Frontiers in Immunology, Numéro 11, 2021, ISSN 1664-3224
Éditeur: Frontiers in Immunology
DOI: 10.3389/fimmu.2020.606266

Novel insights from the Plasmodium falciparum sporozoite-specific proteome by probabilistic integration of 26 studies.

Auteurs: Meerstein-Kessel L, Venhuizen J, Garza D, Proellochs NI, Vos EJ, Obiero JM, et al.
Publié dans: PLoS Comput. Biol., 2021, ISSN 1553-7358
Éditeur: PLOS
DOI: 10.1371/journal.pcbi.1008067

Alpha-v–containing integrins are host receptors for the Plasmodium falciparum sporozoite surface protein, TRAP

Auteurs: Kirsten Dundas, Melanie J. Shears, Yi Sun, Christine S. Hopp, Cecile Crosnier, Tom Metcalf, Gareth Girling, Photini Sinnis, Oliver Billker, Gavin J. Wright
Publié dans: Proceedings of the National Academy of Sciences, Numéro 115/17, 2018, Page(s) 4477-4482, ISSN 0027-8424
Éditeur: National Academy of Sciences
DOI: 10.1073/pnas.1719660115

Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies

Auteurs: Daniel G.W. Alanine, Doris Quinkert, Rasika Kumarasingha, Shahid Mehmood, Francesca R. Donnellan, Nana K. Minkah, Bernadeta Dadonaite, Ababacar Diouf, Francis Galaway, Sarah E. Silk, Abhishek Jamwal, Jennifer M. Marshall, Kazutoyo Miura, Lander Foquet, Sean C. Elias, Geneviève M. Labbé, Alexander D. Douglas, Jing Jin, Ruth O. Payne, Joseph J. Illingworth, David J. Pattinson, David Pulido, Barnab
Publié dans: Cell, Numéro 178/1, 2019, Page(s) 216-228.e21, ISSN 0092-8674
Éditeur: Cell Press
DOI: 10.1016/j.cell.2019.05.025

A Universal Plug-and-Display Vaccine Carrier Based on HBsAg VLP to Maximize Effective Antibody Response

Auteurs: Arianna Marini, Yu Zhou, Yuanyuan Li, Iona J. Taylor, Darren B. Leneghan, Jing Jin, Marija Zaric, David Mekhaiel, Carole A. Long, Kazutoyo Miura, Sumi Biswas
Publié dans: Frontiers in Immunology, Numéro 10, 2019, Page(s) Artiicle 2931, ISSN 1664-3224
Éditeur: Unknown
DOI: 10.3389/fimmu.2019.02931

Pfs230 and Pfs48/45 Fusion Proteins Elicit Strong Transmission-Blocking Antibody Responses Against Plasmodium falciparum

Auteurs: Susheel K. Singh, Susan Thrane, Bishwanath K. Chourasia, Karina Teelen, Wouter Graumans, Rianne Stoter, Geert-Jan van Gemert, Marga G. van de Vegte-Bolmer, Morten A. Nielsen, Ali Salanti, Adam F. Sander, Robert W. Sauerwein, Matthijs M. Jore, Michael Theisen
Publié dans: Frontiers in Immunology, Numéro 10, 2019, Page(s) Article 1256, ISSN 1664-3224
Éditeur: Unknown
DOI: 10.3389/fimmu.2019.01256

Current Challenges in the Identification of Pre-Erythrocytic Malaria Vaccine Candidate Antigens

Auteurs: Paulo Bettencourt
Publié dans: Frontiers in Immunology, Numéro 11, 2020, Page(s) Article 190, ISSN 1664-3224
Éditeur: Unknown
DOI: 10.3389/fimmu.2020.00190

Immunity against sexual stage Plasmodium falciparum and Plasmodium vivax parasites

Auteurs: Roos M. Jong, Surafel K. Tebeje, Lisette Meerstein‐Kessel, Fitsum G. Tadesse, Matthijs M. Jore, Will Stone, Teun Bousema
Publié dans: Immunological Reviews, Numéro 293/1, 2019, Page(s) 190-215, ISSN 0105-2896
Éditeur: Blackwell Publishing Inc.
DOI: 10.1111/imr.12828

Functional Comparison of Blood-Stage Plasmodium falciparum Malaria Vaccine Candidate Antigens

Auteurs: Joseph J. Illingworth, Daniel G. Alanine, Rebecca Brown, Jennifer M. Marshall, Helen E. Bartlett, Sarah E. Silk, Geneviève M. Labbé, Doris Quinkert, Jee Sun Cho, Jason P. Wendler, David J. Pattinson, Lea Barfod, Alexander D. Douglas, Michael W. Shea, Katherine E. Wright, Simone C. de Cassan, Matthew K. Higgins, Simon J. Draper
Publié dans: Frontiers in Immunology, Numéro 10, 2019, Page(s) Article 1254, ISSN 1664-3224
Éditeur: Unknown
DOI: 10.3389/fimmu.2019.01254

Generation of Novel Plasmodium falciparum NF135 and NF54 Lines Expressing Fluorescent Reporter Proteins Under the Control of Strong and Constitutive Promoters

Auteurs: Shinya Miyazaki, Annie S. P. Yang, Fiona J. A. Geurten, Catherin Marin-Mogollon, Yukiko Miyazaki, Takashi Imai, Surendra Kumar Kolli, Jai Ramesar, Severine Chevalley-Maurel, Ahmed M. Salman, Geert-Jan A. van Gemert, Youri M. van Waardenburg, Blandine Franke-Fayard, Adrian V. S. Hill, Robert W. Sauerwein, Chris J. Janse, Shahid M. Khan
Publié dans: Frontiers in Cellular and Infection Microbiology, Numéro 10, 2020, ISSN 2235-2988
Éditeur: Frontiers Media S. A.
DOI: 10.3389/fcimb.2020.00270

CRISPR/Cas9-engineered inducible gametocyte producer lines as a valuable tool for Plasmodium falciparum malaria transmission research

Auteurs: Boltryk SD, Passecker A, Alder A, Carrington E, van de Vegte-Bolmer M, van Gemert G-J, et al
Publié dans: Nature Communications, 2021, ISSN 2041-1723
Éditeur: Nature Publishing Group
DOI: 10.1038/s41467-021-24954-4

Other (1)

A screen for Plasmodium falciparum sporozoite surface protein binding to human hepatocyte surface receptors identifies novel host-pathogen interactions

Auteurs: Rameswara Reddy Segireddy, Kirsten Dundas, Julia Knoeckel, Francis Galaway, Laura Wood, Gavin J Wright, View ORCID ProfileAlexander D Douglas
Publié dans: TBD, Numéro TBD, 2020, Page(s) TBD
Éditeur: TBD
DOI: 10.1101/2020.02.02.929190

Droits de propriété intellectuelle

Patent (4)

MULTIVALENT MALARIA TRANSMISSION-BLOCKING VACCINES

Numéro de demande/publication: 20 20058906
Date: 2020-03-30
Demandeur(s): STATENS SERUM INSTITUT

VACCINE IMMUNOGENS

Numéro de demande/publication: 20 728129
Date: 2020-05-11
Demandeur(s): THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD

VACCINE IMMUNOGENS

Numéro de demande/publication: 20 728129
Date: 2020-05-11
Demandeur(s): THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD

MULTIVALENT MALARIA TRANSMISSION-BLOCKING VACCINES

Numéro de demande/publication: 20 20058906
Date: 2020-03-30
Demandeur(s): STATENS SERUM INSTITUT