Low-Dose SARS-CoV-2 S-Trimer with an Emulsion Adjuvant Induced Th1-Biased Protective Immunity.

During the sustained COVID-19 pandemic, global mass vaccination to achieve herd immunity can prevent further viral spread and mutation. A protein subunit vaccine that is safe, effective, stable, has few storage restrictions, and involves a liable manufacturing process would be advantageous to distribute around the world. Here, we designed and produced a recombinant spike (S)-Trimer that is maintained in a prefusion state and exhibits a high ACE2 binding affinity. Rodents received different doses of S-Trimer (0.5, 5, or 20 µg) antigen formulated with aluminum hydroxide (Alum) or an emulsion-type adjuvant (SWE), or no adjuvant. After two vaccinations, the antibody response, T-cell responses, and number of follicular helper T-cells (Tfh) or germinal center (GC) B cells were assessed in mice; the protective efficacy was evaluated on a Syrian hamster infection model. The mouse studies demonstrated that adjuvating the S-Trimer with SWE induced a potent humoral immune response and Th1-biased cellular immune responses (in low dose) that were superior to those induced by Alum. In the Syrian hamster studies, when S-Trimer was adjuvanted with SWE, higher levels of neutralizing antibodies were induced against live SARS-CoV-2 from the original lineage and against the emergence of variants (Beta or Delta) with a slightly decreased potency. In addition, the SWE adjuvant demonstrated a dose-sparing effect; thus, a lower dose of S-Trimer as an antigen (0.5 µg) can induce comparable antisera and provide complete protection from viral infection. These data support the utility of SWE as an adjuvant to enhance the immunogenicity of the S-Trimer vaccine, which is feasible for further clinical testing.

Monoclonal antibody targeting the conserved region of the SARS-CoV-2 spike protein to overcome viral variants.

Most therapeutic mAbs target the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2. Unfortunately, the RBD is a hot spot for mutations in SARS-CoV-2 variants, which will lead to loss of the neutralizing function of current therapeutic mAbs. Universal mAbs for different variants are necessary. We identified mAbs that recognized the S2 region of the spike protein, which is identical in different variants. The mAbs could neutralize SARS-CoV-2 infection and protect animals from SARS-CoV-2 challenge. After cloning the variable region of the light chain and heavy chain, the variable region sequences were humanized to select a high-affinity humanized mAb, hMab5.17. hMab5.17 protected animals from SARS-CoV-2 challenge and neutralized SARS-CoV-2 variant infection. We further identified the linear epitope of the mAb, which is not mutated in any variant of concern. These data suggest that a mAb recognizing the S2 region of the spike protein will be a potential universal therapeutic mAb for COVID-19.

Effect of Non-lockdown Social Distancing and Testing-Contact Tracing During a COVID-19 Outbreak in Daegu, South Korea, February to April 2020: A Modeling Study.

OBJECTIVE: In Spring 2020, South Korea applied non-lockdown social distancing (avoiding mass gathering and non-essential social engagement, without restricting the movement of people who were not patients or contacts), testing-and-isolation (testing), and tracing-and-quarantine the contacts (contact tracing) to successfully control the first large-scale COVID-19 outbreak outside China. However, the relative contributions of these two interventions remain uncertain. METHODS: We constructed an SEIR model of SARS-CoV-2 transmission (disproportionately through superspreading events) and fit the model to outbreak data in Daegu, South Korea, from February to April 2020. We assessed the effect of non-lockdown social distancing (population-wide control measures) and/or testing-contact tracing (individual-specific control measures), alone or combined, in terms of the basic reproductive number (R0) and the trajectory of the epidemic. RESULTS: The point estimate for baseline R0 is 3.6 (sensitivity analyses range: 2.3 to 5.6). Combined interventions of non-lockdown social distancing and testing-contact tracing can suppress R0 to less than one and rapidly contain the epidemic, even under the worst scenario with a high baseline R0 of 5.6. In contrast, either intervention alone will fail to suppress R0. Non-lockdown social distancing alone just postpones the peak of the epidemic, while testing-contact tracing alone only flattens the curve but does not contain the outbreak. CONCLUSIONS: To successfully control a large-scale COVID-19 outbreak, both non-lockdown social distancing and testing-contact tracing must be implemented. The two interventions are synergistic.

Legal and ethical issues of COVID-19 "Digital Contact Tracing" measures in Taiwan

Objectives: COVID-19 has posed unprecedented challenges to governments and civil society worldwide. Before effective treatments and vaccines become available, nonpharmaceutical interventions (NPIs), including digital contact tracing technologies, are critical for delaying or controlling the spread of COVID-19. This paper investigates the practices, discussions, and legal and ethical issues of the contact tracing measures imposed in Taiwan during the COVID-19 pandemic. Methods: By analyzing official documents from the Ministry of Health and Welfare website, media reports, legal regulations, international organizations' ethical guidelines, and research on contact tracing measures, this paper categorically presents the applications, effectiveness, and legal and ethical concerns of these measures in Taiwan. Results: Although the rates of confirmed cases and deaths from COVID-19 are low in Taiwan, the Electronic Fence of Surveillance, a digital contact tracing measure implemented by the National Health Command Center, was found to lack legal certainty. Some proactive deployments by public and private organizations that have used location-based services, the National Health Insurance system, and the center's data on of the digital footprints of confirmed cases do not meet ethical and scientific validity standards. Oversight mechanisms have not been established, and public reflection has not been addressed. Conclusions: This paper argues that the choice of upholding individual privacy rights versus performing digital contact tracing is not binary. To make digital technologies part of measures against COVID-19, and future public health crises, it is crucial to include diverse experts not only of information technology and biomedicine, but also of epidemiology, public health, law, ethics, and social sciences, as well as civil organizations in the design, application, oversight, and evaluation of new public health technologies.