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May 3rd, 2019
Changing Priorities in vaccinology: Antibiotic Resistance Moving to the Top
Aldo Tagliabue and Rino Rappuoli

Antimicrobial resistance (AMR) is currently the most alarming issue for human health. AMR already causes 700,000 deaths/year. It is estimated that 10 million deaths due to AMR will occur every year after 2050. This equals the number of people dying of cancer every year in present times. International institutions such as G20, World Bank, World Health Organization (WHO), UN General Assembly, European Union, and the UK and USA governments are calling for new antibiotics. To underline this emergency, a list of antibiotic-resistant “priority pathogens” has been published by WHO. It contains 12 families of bacteria that represent the greatest danger for human health. Resistance to multiple antibiotics is particularly relevant for the Gram-negative bacteria present in the list. The ability of these bacteria to develop mechanisms to resist treatment could be transmitted with genetic material, allowing other bacteria to become drug resistant. Although the search for new antimicrobial drugs remains a top priority, the pipeline for new antibiotics is not promising, and alternative solutions are needed. A possible answer to AMR is vaccination. In fact, while antibiotic resistance emerges rapidly, vaccines can lead to a much longer lasting control of infections. New technologies, such as the high-throughput cloning of human B cells from convalescent or vaccinated people, allow for finding new protective antigens (Ags) that could not be identified with conventional technologies. Antibodies produced by convalescent B cell clones can be screened for their ability to bind, block, and kill bacteria, using novel high-throughput microscopy platforms that rapidly capture digital images, or by conventional technologies such as bactericidal, opsono-phagocytosis and FACS assays. Selected antibodies expressed by recombinant DNA techniques can be used for passive immunization in animal models and tested for protection. Antibodies providing the best protection can be employed to identify new Ags and then used for generating highly specific recombinant Fab fragments. Co-crystallization of Ags bound to Fab fragments will allow us to determine the structure and characteristics of new Ags. This structure-based Ag design will bring to a new generation of vaccines able to target previously elusive infections, thereby offering an effective solution to the problem of AMR.

doi: 10.3389/fimmu.2018.01068
Front. Immunol., 30 May 2018
Feb 22nd, 2019
On the predictability of infectious disease outbreaks
Samuel V. Scarpino & Giovanni Petri

Infectious disease outbreaks recapitulate biology: they emerge from the multi-level interaction of hosts, pathogens, and environment. Therefore, outbreak forecasting requires an integrative approach to modeling. While specific components of outbreaks are predictable, it remains unclear whether fundamental limits to outbreak prediction exist. Here, adopting permutation entropy as a model independent measure of predictability, we study the predictability of a diverse collection of outbreaks and identify a fundamental entropy barrier for disease time series forecasting. However, this barrier is often beyond the time scale of single outbreaks, implying prediction is likely to succeed. We show that forecast horizons vary by disease and that both shifting model structures and social network heterogeneity are likely mechanisms for differences in predictability. Our results highlight the importance of embracing dynamic modeling approaches, suggest challenges for performing model selection across long time series, and may relate more broadly to the predictability of complex adaptive systems.

 

Nature Communications, volume 10, Article number: 898 (2019)
May 3rd, 2019
Towards a solution to MERS: protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glycoprotein
Ivy Widjaja, Chunyan Wang, Rien van Haperen, Javier Gutiérrez-Álvarez, Brenda van Dieren, Nisreen M.A. Okba, V. Stalin Raj, Wentao Li, Raul Fernandez-Delgado, Frank Grosveld, Frank J. M. van Kuppeveld, Bart L. Haagmans, Luis Enjuanes, Dubravka Drabek ...

The Middle-East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus that causes severe and often fatal respiratory disease in humans. Efforts to develop antibody-based therapies have focused on neutralizing antibodies that target the receptor binding domain of the viral spike protein thereby blocking receptor binding. Here, we developed a set of human monoclonal antibodies that target functionally distinct domains of the MERS-CoV spike protein. These antibodies belong to six distinct epitope groups and interfere with the three critical entry functions of the MERS-CoV spike protein: sialic acid binding, receptor binding and membrane fusion. Passive immunization with potently as well as with poorly neutralizing antibodies protected mice from lethal MERS-CoV challenge. Collectively, these antibodies offer new ways to gain humoral protection in humans against the emerging MERS-CoV by targeting different spike protein epitopes and functions.

DOI: 10.1080/22221751.2019.1597644
Emerging Microbes & Infections, 2019, 8:1, 516-530

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