Optimizing a deployable high efficacy malaria vaccine

Projektinformationen

OptiMalVax

ID Finanzhilfevereinbarung: 733273

DOI

10.3030/733273

Projekt abgeschlossen

EK-Unterschriftsdatum 9 Dezember 2016

Startdatum 1 Januar 2017

Enddatum 31 Dezember 2022

Finanziert unter

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

Gesamtkosten

€ 23 741 228,75

EU-Beitrag

€ 20 050 441,25

Koordiniert durch

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

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Leistungen

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

Veröffentlichungen

Peer reviewed articles (15)

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

Autoren: 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
Veröffentlicht in: Frontiers in Immunology, 2022, ISSN 1664-3224
Herausgeber: Frontiers Media SA
DOI: 10.3389/fimmu.2022.909060

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

Autoren: 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
Veröffentlicht in: PLOS ONE, Ausgabe 16/7, 2021, Seite(n) e0254498, ISSN 1932-6203
Herausgeber: Public Library of Science
DOI: 10.1371/journal.pone.0254498

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

Autoren: 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
Veröffentlicht in: NPJ Vaccines, 2021, ISSN 2059-0105
Herausgeber: Springer Nature
DOI: 10.1038/s41541-021-00383-8

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

Autoren: Ko KT, Lennartz F, Mekhaiel D, Guloglu B, Marini A, Deuker DJ, Long CA, Jore MM, Miura K, Biswas S, Higgins MK
Veröffentlicht in: Nature Communications, 2022, ISSN 2041-1723
Herausgeber: 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

Autoren: 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
Veröffentlicht in: Frontiers in Immunology, Ausgabe 11, 2021, ISSN 1664-3224
Herausgeber: Frontiers in Immunology
DOI: 10.3389/fimmu.2020.606266

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

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

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

Autoren: Kirsten Dundas, Melanie J. Shears, Yi Sun, Christine S. Hopp, Cecile Crosnier, Tom Metcalf, Gareth Girling, Photini Sinnis, Oliver Billker, Gavin J. Wright
Veröffentlicht in: Proceedings of the National Academy of Sciences, Ausgabe 115/17, 2018, Seite(n) 4477-4482, ISSN 0027-8424
Herausgeber: National Academy of Sciences
DOI: 10.1073/pnas.1719660115

Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies

Autoren: 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
Veröffentlicht in: Cell, Ausgabe 178/1, 2019, Seite(n) 216-228.e21, ISSN 0092-8674
Herausgeber: 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

Autoren: 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
Veröffentlicht in: Frontiers in Immunology, Ausgabe 10, 2019, Seite(n) Artiicle 2931, ISSN 1664-3224
Herausgeber: Unknown
DOI: 10.3389/fimmu.2019.02931

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

Autoren: 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
Veröffentlicht in: Frontiers in Immunology, Ausgabe 10, 2019, Seite(n) Article 1256, ISSN 1664-3224
Herausgeber: Unknown
DOI: 10.3389/fimmu.2019.01256

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

Autoren: Paulo Bettencourt
Veröffentlicht in: Frontiers in Immunology, Ausgabe 11, 2020, Seite(n) Article 190, ISSN 1664-3224
Herausgeber: Unknown
DOI: 10.3389/fimmu.2020.00190

Immunity against sexual stage Plasmodium falciparum and Plasmodium vivax parasites

Autoren: Roos M. Jong, Surafel K. Tebeje, Lisette Meerstein‐Kessel, Fitsum G. Tadesse, Matthijs M. Jore, Will Stone, Teun Bousema
Veröffentlicht in: Immunological Reviews, Ausgabe 293/1, 2019, Seite(n) 190-215, ISSN 0105-2896
Herausgeber: Blackwell Publishing Inc.
DOI: 10.1111/imr.12828

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

Autoren: 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
Veröffentlicht in: Frontiers in Immunology, Ausgabe 10, 2019, Seite(n) Article 1254, ISSN 1664-3224
Herausgeber: 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

Autoren: 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
Veröffentlicht in: Frontiers in Cellular and Infection Microbiology, Ausgabe 10, 2020, ISSN 2235-2988
Herausgeber: 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

Autoren: Boltryk SD, Passecker A, Alder A, Carrington E, van de Vegte-Bolmer M, van Gemert G-J, et al
Veröffentlicht in: Nature Communications, 2021, ISSN 2041-1723
Herausgeber: 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

Autoren: Rameswara Reddy Segireddy, Kirsten Dundas, Julia Knoeckel, Francis Galaway, Laura Wood, Gavin J Wright, View ORCID ProfileAlexander D Douglas
Veröffentlicht in: TBD, Ausgabe TBD, 2020, Seite(n) TBD
Herausgeber: TBD
DOI: 10.1101/2020.02.02.929190

Rechte des geistigen Eigentums

Patent (4)

MULTIVALENT MALARIA TRANSMISSION-BLOCKING VACCINES

Antrags-/Publikationsnummer: 20 20058906
Datum: 2020-03-30
Antragsteller: STATENS SERUM INSTITUT

VACCINE IMMUNOGENS

Antrags-/Publikationsnummer: 20 728129
Datum: 2020-05-11
Antragsteller: THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD

VACCINE IMMUNOGENS

Antrags-/Publikationsnummer: 20 728129
Datum: 2020-05-11
Antragsteller: THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD

MULTIVALENT MALARIA TRANSMISSION-BLOCKING VACCINES

Antrags-/Publikationsnummer: 20 20058906
Datum: 2020-03-30
Antragsteller: STATENS SERUM INSTITUT