Antibodies generated in vitro and in vivo elucidate design of a thermostable ADDomer COVID-19 nasal nanoparticle vaccine (preprint)

COVID-19 continues to damage populations, communities and economies worldwide. Vaccines have reduced COVID-19-related hospitalisations and deaths, primarily in developed countries. Persisting infection rates, and highly transmissible SARS-CoV-2 Variants of Concern (VOCs) causing repeat and breakthrough infections, underscore the ongoing need for new treatments to achieve a global solution. Based on ADDomer, a self-assembling protein nanoparticle scaffold, we created ADDoCoV, a thermostable COVID-19 candidate vaccine displaying multiple copies of a SARS-CoV-2 receptor binding motif (RBM)-derived epitope. In vitro generated neutralising nanobodies combined with molecular dynamics (MD) simulations and electron cryo-microscopy (cryo-EM) established authenticity and accessibility of the epitopes displayed. A Gigabody comprising multimerized nanobodies prevented SARS-CoV-2 virion attachment with picomolar EC50. Antibodies generated by immunising mice cross-reacted with VOCs including Delta and Omicron. Our study elucidates nasal administration of ADDomer-based nanoparticles for active and passive immunisation against SARS-CoV-2 and provides a blueprint for designing nanoparticle reagents to combat respiratory viral infections.

PG78 A multi-professional education programme: simulation enhances staff preparedness for dealing with Covid 19 pandemic

IntroductionThe novel coronavirus – Covid 19 pandemic has presented huge challenges to healthcare provision worldwide. The virus is an unknown quantity. The multisystem pathology and highly contagious nature, has caused healthcare capacity to become overwhelmed during the peak. Learning from other countries’ experience, at Northern Lincolnshire and Goole hospital Trust we created a multi-pronged approach to rapidly educate staff and test the clinical set up for managing a surge of patients with Covid 19.1MethodsIn-situ simulations were conducted in the Emergency departments, Respiratory wards and ICU, evaluating the trust logistics and clinical management of the acutely deteriorating patient.A Covid 19 education package was developed comprising lectures covering pathophysiology, assessment, decision making tools, management protocols and operating procedures. Theory was consolidated with rotating small group simulations in vacant operating theatres. Familiarisation with Personal Protective Equipment (PPE), Public Health England guidance and practising donning and doffing started the session. Utilising both full body manikins, and part task trainers we simulated the following suspected/Covid 19 clinical scenarios;Emergency intubation, ventilation and transferConducting anaesthesia and surgeryCaesarean section, and insertion of labour EpiduralCardiac arrestProning and unproning the ventilated patient in ICUResultsSessions were run eight per day, over two weeks, populated with eight multi-professional staff (approximately fifty/day). Attendees included doctors from critical care, surgery, Emergency and respiratory medicine, all theatre and recovery nursing and operating department practitioners. In -situ scenarios elucidated logistical challenges relating to space, PPE, drugs, equipment and technical aspects when performing emergency intubation in situ.DiscussionWith the Covid 19 pandemic rapidly escalating, a coordinated approach of assessing our trust’s logistics and clinical protocols was needed, as well as effective education, cross speciality and health care professions, together with cross skilling in practical procedures. Speed of delivery was imperative and this programme was created and rolled out within two weeks. In North Lincolnshire Covid 19 infection rates remained slower that many UK areas, permitting a timely window of training. Challenges faced were the availability of training locations, spacious enough to permit social distancing, the differing needs of healthcare professionals, and the frequent changes to national guidance. Simulation both in -situ and class room based together with clinical skills drills was invaluable in facilitating the learning. Verbal reports from participants demonstrated decreased anxiety, and improved confidence when faced with suspected/COVID patients, and familiarisation with the PPE guidance.2Referenceshttps://www.who.int/emergencies/diseases/novel-coronavirus-2019/training/simulation-exercise.Simulation-based training programme and preparedness testing for COVID-19 using system integration methodology HMS. Lababidi et al BMJ Simulation and Technology Enhanced learning 27 May 2020 online