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Optimizing a deployable high efficacy malaria vaccine

Deliverables

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

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

4.5 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

3.1 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

7.6 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

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

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

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Publications

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

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

Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies

Author(s): 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
Published in: Cell, Issue 178/1, 2019, Page(s) 216-228.e21, ISSN 0092-8674
DOI: 10.1016/j.cell.2019.05.025

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

Author(s): 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
Published in: Frontiers in Immunology, Issue 10, 2019, Page(s) Artiicle 2931, ISSN 1664-3224
DOI: 10.3389/fimmu.2019.02931

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

Author(s): 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
Published in: Frontiers in Immunology, Issue 10, 2019, Page(s) Article 1256, ISSN 1664-3224
DOI: 10.3389/fimmu.2019.01256

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

Author(s): Paulo Bettencourt
Published in: Frontiers in Immunology, Issue 11, 2020, Page(s) Article 190, ISSN 1664-3224
DOI: 10.3389/fimmu.2020.00190

Immunity against sexual stage Plasmodium falciparum and Plasmodium vivax parasites

Author(s): Roos M. Jong, Surafel K. Tebeje, Lisette Meerstein‐Kessel, Fitsum G. Tadesse, Matthijs M. Jore, Will Stone, Teun Bousema
Published in: Immunological Reviews, Issue 293/1, 2019, Page(s) 190-215, ISSN 0105-2896
DOI: 10.1111/imr.12828

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

Author(s): 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
Published in: Frontiers in Immunology, Issue 10, 2019, Page(s) Article 1254, ISSN 1664-3224
DOI: 10.3389/fimmu.2019.01254

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

Author(s): Rameswara Reddy Segireddy, Kirsten Dundas, Julia Knoeckel, Francis Galaway, Laura Wood, Gavin J Wright, View ORCID ProfileAlexander D Douglas
Published in: TBD, Issue TBD, 2020, Page(s) TBD
DOI: 10.1101/2020.02.02.929190