Malaria Vaccines for the World 2019: Day 3
MESA Correspondents bring you cutting-edge coverage from the 5th International Conference on Malaria Vaccines for the World (MVW).
SESSION 9: LATEST ADVANCES IN VACCINES AND CHMI FOR P. VIVAX
Hernando A. del Portillo (ISGlobal Barcelona Institute for Global Health) presented the potential for using reticulocyte-derived exosomes as a vaccine delivery platform against P. vivax and discussed novel antigen discovery. He demonstrated proof of concept in a rodent model and in human studies of plasma-derived vesicles from natural infections that showed the presence of parasite cargo associated with CD71+ EVs. These human reticulocyte-derived exosomes contain MHC Class I antigens that are actively taken up by myeloid dendritic cells and thus can be presented to the immune system.
Angela M. Minassian (University of Oxford) presented the establishment of a P. vivax sporozoite and blood-stage Controlled Human Malaria Infections (CHMI) in healthy UK adults. This is the first time that the mosquito-bite and blood-stage CHMI have been done in Europe. Using a characterized Thai isolate, the team has successfully established a new P. vivax blood-bank that will be available to the research community for CHMI. Next, they will carry out vaccine and immunology studies and prepare new blood banks for other Plasmodium isolates.
Chetan E. Chitnis (International Centre for Genetic Engineering and Biotechnology, New Delhi and Institut Pasteur, Paris) presented on the development of a vaccine designed to induce antibodies to block the interaction of PvDBP (Duffy Binding Protein) region II with DARC (Duffy-Antigen Chemokine Receptor), which is essential for P. vivax invasion of reticulocytes. The PvDBPII+GLA-SE vaccine was tested in malaria naive, healthy Indian adults and elicited strain transcending inhibitory antibodies. Next, Tom Rawlinson (University of Oxford) explained the molecular basis of the inhibition of P. vivax reticulocyte invasion by a vaccine-induced neutralizing human monoclonal antibody (mAb). This mAb was selected based on the performance on growth inhibition with transgenic P. knowlesi parasites expressing PvDBP and ex vivo invasion assays with Thai P. vivax clinical isolates. The team has also described the binding site of this mAb to DARC, suggesting that the binding to the epitope may hinder the interaction of PvDBP with DARC, preventing the invasion.
SESSION 10: NOVEL APPROACHES TO ANTIGEN DISCOVERY, VACCINE DELIVERY AND ADJUVANTS
Rana Chattopadhyay (Food and Drug Administration (FDA), USA) gave an overview of regulatory aspects relating to malaria vaccines by the U.S. FDA and provided an outline of the key regulatory stages and steps in vaccine development. He reviewed the need to demonstrate safety, effectiveness and manufacturing consistency for licensure, and stressed that there are opportunities to interact with the FDA at all stages of vaccine development.
Mark Howarth (University of Oxford) presented on bioconjugation techniques and capabilities via Spy Technology, like “bacterial superglue” that can accelerate malaria vaccine generation. SpyTag and SpyCatcher can be used in a variety of ways, such as SpyCatcher-mi3 protein capabilities for “Plug-and-Display” which creates a simple way to turn protein antigen into immunogenic VLPs (virus-like particles).
Evelina Angov (Walter Reed Army Institute of Research) presented a strategic overview of Walter Reed Army Institute of Research’s next generation adjuvanted P. falciparum circumsporozoite protein (CSP) vaccine candidates under clinical development. FMP013 is a soluble recombinant full length CSP. FMP014 is a self-assembling protein nanoparticle, recombinant with partial CSP sequences. Both are formulated with the Army Liposomal Formulation + QS-21. Preclinical studies with these candidates in mice, rhesus macaques and rabbit show safety, good tolerability and immunogenicity.
Louise Bjerkan (University of Oslo) presented the Vaccibody, a DNA-based platform for antigen presenting cells (APC)-targeted vaccination against RH5. She showed that vaccination in mice induces IFNγ T cell responses to RH5 epitopes and RH5-specific neutralizing antibodies, which are efficient in blocking invasion of P. falciparum in growth inhibition assays. This platform can be translated into larger animals, and has shown to be safe in clinical trials in humans with other infectious diseases and cancer. She concluded that targeting RH5 to APC potentiates viral vector immunization against malaria.
Sarah E. Silk (University of Oxford) (on behalf of Ally Olotu (Health Institute and KEMRI-Wellcome Trust Research Programme)) presented the clinical trial assessing safety and immunogenicity of ChAd63 and MVA expressing P. falciparum RH5 in Tanzanian adults, young children and infants. The ChAd63/MVA RH5 appears to be safe and the trial will be unblinded soon.
Takafumi Tsuboi (Ehime University, Japan) stressed the need for novel malaria vaccine candidates and presented the innovative Japanese technology of wheat germ cell-free protein synthesis system in the context of vaccine development. With immunoscreening and functional approaches, he prioritized the blood-stage PfRipr protein, which showed to be a highly conserved top-rank vaccine candidate.
Paulo Bettencourt (University of Oxford) finished the session by discussing the identification of novel antigens presented by MHC (major histocompatibility complex) class I using immunopeptidomics platforms for potential vaccines against malaria. This new tool for antigen discovery has been able to identify a new family of antigens, the 40S and 60S ribosomal proteins as vaccine candidates. Homology between humans and Plasmodium ribosomal proteins is 60%, leaving the other 40% available for exploration.
Simon J. Draper (University of Oxford) thanked the speakers, session chairs, poster presenters, and meeting management team. He gave a summary of the conference by comparing the topics covered this year 2019, with the content of the very first Malaria Vaccines for the World meeting in 2007 and commented on how remarkable the advances in the malaria vaccine field have been since then.
Closing remarks by Simon J. Draper: MVW 2007 and 2019
This daily report has been written by Rebeca Santano and Robert Mitchell (ISGlobal) as part of the MESA Correspondents program. Senior editorial support and expertise have been provided by Dr Carlota Dobaño (ISGlobal).