Pre-clinical Vaccine Development for Emerging and Re-emerging Infectious Diseases

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The Virology Core has collaborated with other intramural NIAID labs help to develop a pan-coronaviruses spike protein subunit vaccine and a re-emerging infectious diseases, EV-D68. During the past year, we focused on developing the vaccine vaccines against most subecoviruses or beta-coronaviruses. We successfully constructed hybrid immunogens of the MERS-CoV Spike or the subunits of the spike, RBD or S1, fused with SARS-CoV2 spike or its subunit proteins tandemly. The hybrid immunogens contained both epitopes of the two viruses in one protein. In addition, we also tried to load the target immunogen proteins on various VLPs to form potentially more immunogenic vaccine candidates. The purified hybrid proteins, loaded VLPs and the plasmid DNA encoding those immunogens were tested in animals. Small animal studies for evaluating the potency of the candidates are actively on-going. Another round of designs and modification are on-going and evaluation of the modified vaccine designs in animal models will perform soon. For continuing isolation of the high potency and breadth of anti-Coronavirus monoclonal antibody (mAb) from immunized animals, we are using specific spike subunit probes (S2P spike, S1 or RBD) for screening and cloning B cells from Covid-19 vaccine immunized animals. Some mAbs specific binding to various Covid-19 emerging variants and other coronaviruses have been successfully isolated. We continue doing more screening assays, including sequencing, EM and pseudoviruses neutralizing of covid-19 variants and different coronaviruses to characterize all those mAbs. In addition, we involved in vaccine development of re-emerging infectious diseases. One recent target is the enterovirus D68 (EV-D68) which causes severe respiratory illness in children. we demonstrate that EV-D68 virus-like particle (VLP) vaccines elicit a protective neutralizing antibody against homologous and heterologous EV-D68 subclades. VLP based on a B1 subclade 2014 outbreak strain elicited comparable B1 EV-D68 neutralizing activity as an inactivated viral particle vaccine in mice. Our results suggest that both vaccine strain and adjuvant selection are critical elements for improving the breadth of protective immunity against EV-D68.