• Accelerating Development of SARS-CoV-2 Vaccines — The Role for Controlled Human Infection Models

      Deming, M.E.; Michael, N.L.; Neuzil, K.M. (Massachusetts Medical Society, 2020-07-01)
    • Durability of Responses after SARS-CoV-2 mRNA-1273 Vaccination.

      Widge, Alicia T; Rouphael, Nadine G; Jackson, Lisa A; Anderson, Evan J; Roberts, Paul C; Makhene, Mamodikoe; Chappell, James D; Denison, Mark R; Stevens, Laura J; Pruijssers, Andrea J; et al. (Massachusetts Medical Society, 2020-12-03)
    • Ethical dilemmas related to the covid-19 pandemic. A perspective. [Perspectiva de los dilemas éticos relacionados con la pandemia covid-19.]

      Vizcaíno, G.; Esparza, J. (Instituto de Investigaciones Clinicas, 2020)
      Facing the SARS-CoV-2 pandemic, known worldwide as COVID-19, constitutes a huge challenge, which must be addressed on multiple aspects of this disease. It is surprising how quickly the SARS-CoV-2 virus has spread globally, it is the pandemic that today occupies all the world attention not only in the medical epidemiological aspects but also in its consequences on geopolitics, the economy and society in general. The scientific information since the pandemic was carried out has been increasing daily in a remarkable way, its epidemiology, mode of transmission, clinical manifestations, laboratory diagnosis, allopathic medical treatments have been published, and several vaccines are on-going in phase 3 from various laboratories in different countries as a measure to the prevention of this disease. In addition, this pandemic brings together a series of ethical dilemmas both in public health decisions, vulnerable populations, research protocols and in the development in the health care of patients affected by this infection. The resolution of the ethical conflicts that have been arisen in the COVID-19 pandemic, should take as reference the Bioethical guidelines published by international organizations (WHO/PAHO) and centers, national or institutional committees dedicated to the field of Bioethics. This would allow responsible action in the face of the pandemic without harming human rights and the individual and social well-being. Copyright 2020, Instituto de Investigaciones Clinicas. All rights reserved.
    • Evaluation of a recombination-resistant coronavirus as a broadly applicable, rapidly implementable vaccine platform

      Graham, R.L.; Deming, D.J.; Deming, M.E. (Nature Research, 2018)
      Emerging and re-emerging zoonotic viral diseases are major threats to global health, economic stability, and national security. Vaccines are key for reducing coronaviral disease burden; however, the utility of live-attenuated vaccines is limited by risks of reversion or repair. Because of their history of emergence events due to their prevalence in zoonotic pools, designing live-attenuated coronavirus vaccines that can be rapidly and broadly implemented is essential for outbreak preparedness. Here, we show that coronaviruses with completely rewired transcription regulatory networks (TRNs) are effective vaccines against SARS-CoV. The TRN-rewired viruses are attenuated and protect against lethal SARS-CoV challenge. While a 3-nt rewired TRN reverts via second-site mutation upon serial passage, a 7-nt rewired TRN is more stable, suggesting that a more extensively rewired TRN might be essential for avoiding growth selection. In summary, rewiring the TRN is a feasible strategy for limiting reversion in an effective live-attenuated coronavirus vaccine candidate that is potentially portable across the Nidovirales order. Copyright 2018, The Author(s).
    • Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo

      Luke, T.; Coleman, C.M.; Frieman, M.B. (American Association for the Advancement of Science, 2016)
      As of 13 November 2015, 1618 laboratory-confirmed human cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, including 579 deaths, had been reported to the World Health Organization. No specific preventive or therapeutic agent of proven value against MERS-CoV is currently available. Public Health England and the International Severe Acute Respiratory and Emerging Infection Consortium identified passive immunotherapy with neutralizing antibodies as a treatment approach that warrants priority study. Two experimental MERS-CoV vaccines were used to vaccinate two groups of transchromosomic (Tc) bovines that were genetically modified to produce large quantities of fully human polyclonal immunoglobulin G (IgG) antibodies. Vaccination with a clade A ?-irradiated whole killed virion vaccine (Jordan strain) or a clade B spike protein nanoparticle vaccine (Al-Hasa strain) resulted in Tc bovine sera with high enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody titers in vitro. Two purified Tc bovine human IgG immunoglobulins (Tc hIgG), SAB-300 (produced after Jordan strain vaccination) and SAB-301 (produced after Al-Hasa strain vaccination), also had high ELISA and neutralizing antibody titers without antibody- dependent enhancement in vitro. SAB-301 was selected for in vivo and preclinical studies. Administration of single doses of SAB-301 12 hours before or 24 and 48 hours after MERS-CoV infection (Erasmus Medical Center 2012 strain) of Ad5-hDPP4 receptor-transduced mice rapidly resulted in viral lung titers near or below the limit of detection. Tc bovines, combined with the ability to quickly produce Tc hIgG and develop in vitro assays and animal model(s), potentially offer a platform to rapidly produce a therapeutic to prevent and/or treat MERSCoV infection and/or other emerging infectious diseases.