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Jun 30th, 2020
ZAPI modular vaccine design approach as an answer to pandemics / panzootics threats
Jean-Christophe AUDONNET, BIAH, ZAPI coordinator
"Pandemics! A One Health view of Emerging Infectious Diseases", organized by H4A, CWG & STAR-IDAZ
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May 29th, 2020
Particulate multivalent presentation of the receptor binding domain induces protective immune responses against MERS-CoV
Nisreen M. A. Okba, Ivy Widjaja, Brenda van Dieren, Andrea Aebischer, Geert van Amerongen, Leon de Waal, Koert J. Stittelaar, Debby Schipper, Byron Martina,Judith M. A. van den Brand, Martin Beer, Berend-Jan Bosch & Bart L. Haagmans

Middle East respiratory syndrome coronavirus (MERS-CoV) is a WHO priority pathogen for which vaccines are urgently needed. Using an immune-focusing approach, we created self-assembling particles multivalently displaying critical regions of the MERS-CoV spike protein ─fusion peptide, heptad repeat 2, and receptor binding domain (RBD) ─ and tested their immunogenicity and protective capacity in rabbits. Using a “plug-and-display” SpyTag/SpyCatcher system, we coupled RBD to lumazine synthase (LS) particles producing multimeric RBD-presenting particles (RBD-LS). RBD-LS vaccination induced antibody responses of high magnitude and quality (avidity, MERS-CoV neutralizing capacity, and mucosal immunity) with cross-clade neutralization. The antibody responses were associated with blocking viral replication and upper and lower respiratory tract protection against MERS-CoV infection in rabbits. This arrayed multivalent presentation of the viral RBD using the antigen-SpyTag/LS-SpyCatcher is a promising MERS-CoV vaccine candidate and this platform may be applied for the rapid development of vaccines against other emerging viruses such as SARS-CoV-2.

Emerging Microbes & Infections Volume 9, 2020 - Issue 1, Pages 1080-1091
Nov 1st, 2018
HIV-1 vaccine design through minimizing envelope metastability
Linling He, Sonu Kumar, Joel D. Allen, Deli Huang, Xiaohe Lin, Colin J. Mann, Karen L. Saye-Francisco, Jeffrey Copps, Anita Sarkar, Gabrielle S. Blizard, Gabriel Ozorowski, Devin Sok, Max Crispin, Andrew B. Ward et al.

Overcoming envelope metastability is crucial to trimer-based HIV-1 vaccine design. Here, we present a coherent vaccine strategy by minimizing metastability. For 10 strains across five clades, we demonstrate that the gp41 ectodomain (gp41ECTO) is the main source of envelope metastability by replacing wild-type gp41ECTO with BG505 gp41ECTO of the uncleaved prefusion-optimized (UFO) design. These gp41ECTO-swapped trimers can be produced in CHO cells with high yield and high purity. The crystal structure of a gp41ECTO-swapped trimer elucidates how a neutralization-resistant tier 3 virus evades antibody recognition of the V2 apex. UFO trimers of transmitted/founder viruses and UFO trimers containing a consensus-based ancestral gp41ECTO suggest an evolutionary root of metastability. The gp41ECTO-stabilized trimers can be readily displayed on 24- and 60-meric nanoparticles, with incorporation of additional T cell help illustrated for a hyperstable 60-mer, I3-01. In mice and rabbits, these gp140 nanoparticles induced tier 2 neutralizing antibody responses more effectively than soluble trimers.

Sci Adv. 2018 Nov; 4(11): eaau6769. doi: 10.1126/sciadv.aau6769
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