Comparative performance of between-population vaccine allocation strategies with applications for emerging pandemics.

Vaccine allocation decisions during emerging pandemics have proven to be challenging due to competing ethical, practical, and political considerations. Complicating decision making, policy makers need to consider vaccine allocation strategies that balance needs both within and between populations. When vaccine stockpiles are limited, doses should be allocated in locations to maximize their impact. Using a susceptible-exposed-infectious-recovered (SEIR) model we examine optimal vaccine allocation decisions across two populations considering the impact of characteristics of the population (e.g., size, underlying immunity, heterogeneous risk structure, interaction), vaccine (e.g., vaccine efficacy), pathogen (e.g., transmissibility), and delivery (e.g., varying speed and timing of rollout). Across a wide range of characteristics considered, we find that vaccine allocation proportional to population size (i.e., pro-rata allocation) performs either better or comparably to nonproportional allocation strategies in minimizing the cumulative number of infections. These results may argue in favor of sharing of vaccines between locations in the context of an epidemic caused by an emerging pathogen, where many epidemiologic characteristics may not be known.

Novel case of Candida auris in the Veterans Health Administration and in the state of South Carolina.

The emerging pathogen Candida auris poses major infection prevention challenges as the organism can remain on surfaces for unknown timeframes and can cause severe illness. These challenges are exacerbated in the health care environment with potential spread to a vulnerable population. This report describes the Columbia Veterans Administration Health Care System's encounter with this significant pathogen beginning in October 2020 during the COVID19 pandemic.

Rapid and reliable inactivation protocols for the diagnostics of emerging viruses: The example of SARS-CoV-2 and monkeypox virus.

The emergence and sustained transmission of novel pathogens are exerting an increasing demand on the diagnostics sector worldwide, as seen with the ongoing severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic and the more recent public health concern of monkeypox virus (MPXV) since May 2022. Appropriate and reliable viral inactivation measures are needed to ensure the safety of personnel handling these infectious samples. In the present study, seven commercialized diagnosis buffers, heat (56°C and 60°C), and sodium dodecyl sulfate detergent (2.0%, 1.0%, and 0.5% final concentrations) were tested against infectious SARS-CoV-2 and MPXV culture isolates on Vero cell culture. Cytopathic effects were observed up to 7 days postinoculation and viral load evolution was measured by semiquantitative polymerase chain reaction. The World Health Organization recommends an infectious titer reduction of at least 4 log10 . As such, the data show efficacious SARS-CoV-2 inactivation by all investigated methods, with >6.0 log10 reduction. MPXV inactivation was also validated with all investigated methods with 6.9 log10 reductions, although some commercial buffers required a longer incubation period to yield complete inactivation. These results are valuable for facilities, notably those without biosafety level-3 capabilities, that need to implement rapid and reliable protocols common against both SARS-CoV-2 and MPXV.

Nanopore Genome Sequencing and Variant Analysis of the Susceptible Candida auris Strain L1537/2020, Salvador, Brazil.

Candida auris has been reported worldwide, but only in December 2020, the first strain from a COVID-19 patient in Brazil was isolated. Here, we describe the genome sequence of this susceptible C. auris strain and performed variant analysis of the genetic relatedness with strains from other geographic localities.

Vaccinomics: a future avenue for vaccine development against emerging pathogens.

INTRODUCTION: Vaccines are a major achievement in medical sciences, but the development of more effective vaccines against infectious diseases is essential for prevention and control of emerging pathogens worldwide. The application of omics technologies has advanced vaccinology through the characterization of host-vector-pathogen molecular interactions and the identification of candidate protective antigens. However, major challenges such as host immunity, pathogen and environmental factors, vaccine efficacy and safety need to be addressed. Vaccinomics provides a platform to address these challenges and improve vaccine efficacy and safety. AREAS COVERED: In this review, we summarize current information on vaccinomics and propose quantum vaccinomics approaches to further advance vaccine development through the identification and combination of antigen protective epitopes, the immunological quantum. The COVID-19 pandemic caused by SARS-CoV-2 is an example of emerging infectious diseases with global impact on human health. EXPERT OPINION: Vaccines are required for the effective and environmentally sustainable intervention for the control of emerging infectious diseases worldwide. Recent advances in vaccinomics provide a platform to address challenges in improving vaccine efficacy and implementation. As proposed here, quantum vaccinomics will contribute to vaccine development, efficacy, and safety by facilitating antigen combinations to target pathogen infection and transmission in emerging infectious diseases.

Genome Editing Technologies as Cellular Defense Against Viral Pathogens.

Viral infectious diseases are significant threats to the welfare of world populations. Besides the widespread acute viral infections (e.g., dengue fever) and chronic infections [e.g., those by the human immunodeficiency virus (HIV) and hepatitis B virus (HBV)], emerging viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pose great challenges to the world. Genome editing technologies, including clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) proteins, zinc-finger nucleases (ZFNs), and transcription activator-like effector nucleases (TALENs), have played essential roles in the study of new treatment for viral infectious diseases in cell lines, animal models, and clinical trials. Genome editing tools have been used to eliminate latent infections and provide resistance to new infections. Increasing evidence has shown that genome editing-based antiviral strategy is simple to design and can be quickly adapted to combat infections by a wide spectrum of viral pathogens, including the emerging coronaviruses. Here we review the development and applications of genome editing technologies for preventing or eliminating infections caused by HIV, HBV, HPV, HSV, and SARS-CoV-2, and discuss how the latest advances could enlighten further development of genome editing into a novel therapy for viral infectious diseases.

Perspectives on passive antibody therapy and peptide-based vaccines against emerging pathogens like SARS-CoV-2.

The current epidemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is raising awareness of the need to act faster when dealing with new pathogens. Exposure to an emerging pathogen generates an antibody response that can be used for preventing and treating the infection. These antibodies might have a high specificity to a target, few side effects, and are useful in the absence of an effective vaccine for treating immunocompromised individuals. The approved antibodies against the receptor-binding domain (RBD) of the viral spike protein of SARS-CoV-2 (e.g., regdanvimab, bamlanivimab, etesevimab, and casirivimab/imdevimab) have been selected from the antibody repertoire of B cells from convalescent patients using flow cytometry, next-generation sequencing, and phage display. This encourages use of these techniques especially phage display, because it does not require expensive types of equipment and can be performed on the lab bench, thereby making it suitable for labs with limited resources. Also, the antibodies in blood samples from convalescent patients can be used to screen pre-made peptide libraries to identify epitopes for vaccine development. Different types of vaccines against SARS-CoV-2 have been developed, including inactivated virus vaccines, mRNA-based vaccines, non-replicating vector vaccines, and protein subunits. mRNA vaccines have numerous advantages over existing vaccines, such as efficacy, ease of manufacture, safety, and cost-effectiveness. Additionally, epitope vaccination may constitute an attractive strategy to induce high levels of antibodies against a pathogen and phages might be used as immunogenic carriers of such peptides. This is a point worth considering further, as phage-based vaccines have been shown to be safe in clinical trials and phages are easy to produce and tolerate high temperatures. In conclusion, identification of the antibody repertoire of recovering patients, and the epitopes they recognize, should be an attractive alternative option for developing therapeutic and prophylactic antibodies and vaccines against emerging pathogens.

Toolkit for Quickly Generating and Characterizing Molecular Probes Specific for SARS-CoV-2 Nucleocapsid as a Primer for Future Coronavirus Pandemic Preparedness.

Generating and characterizing immunoreagents to enable studies of novel emerging viruses is an area where ensembles of synthetic genes, recombinant antibody pipelines, and modular antibody-reporter fusion proteins can respond rapidly. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread through the global population causing widespread morbidity, mortality, and socioeconomic chaos. Using SARS-CoV-2 as our model and starting with a gBlocks encoded nucleocapsid (N) gene, we purified recombinant protein from E. coli, to serve as bait for selecting semisynthetic nanobodies from our Nomad single-pot library. Clones were isolated in days and first fused to Gaussia luciferase to determine EC50 in the tens of nM range, and second fused to the ascorbate peroxidase derivative APEX2 for sensitive detection of SARS-CoV-2 infected cells. To generate inherently fluorescent immunoreagents, we introduce novel periplasmic sdAb fusions made with mNeonGreen and mScarlet-I, which were produced at milligram amounts. The fluorescent fusion proteins enabled concise visualization of SARS-CoV-2 N in the cytoplasm but not in the nucleus 24 h post infection, akin to the distribution of SARS-CoV N, thereby validating these useful imaging tools. SdAb reactivity appeared specific to SARS-CoV-2 with very much weaker binding to SARS-CoV, and no noticeable cross-reactivity to a panel of overexpressed human codon optimized N proteins from other CoV. High periplasmic expression levels and in silico immortalization of the nanobody constructs guarantees a cost-effective and reliable source of SARS-CoV-2 immunoreagents. Our proof-of-principle study should be applicable to known and newly emerging CoV to broaden the tools available for their analysis and help safeguard human health in a more proactive than reactive manner.

Mass Spectrometry Techniques in Emerging Pathogens Studies: COVID-19 Perspectives.

As corona virus disease 2019 (COVID-19) is a rapidly growing public health crisis across the world, our knowledge of meaningful diagnostic tests and treatment for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is still evolving. This novel coronavirus disease COVID-19 can be diagnosed using RT-PCR, but inadequate access to reagents, equipment, and a nonspecific target has slowed disease detection and management. Precision medicine, individualized patient care, requires suitable diagnostics approaches to tackle the challenging aspects of viral outbreaks where many tests are needed in a rapid and deployable approach. Mass spectrometry (MS)-based technologies such as proteomics, glycomics, lipidomics, and metabolomics have been applied in disease outbreaks for identification of infectious disease agents such as virus and bacteria and the molecular phenomena associated with pathogenesis. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/MS) is widely used in clinical diagnostics in the United States and Europe for bacterial pathogen identification. Paper spray ionization mass spectrometry (PSI-MS), a rapid ambient MS technique, has recently open a new opportunity for future clinical investigation to diagnose pathogens. Ultra-high-pressure liquid chromatography coupled high-resolution mass spectrometry (UHPLC-HRMS)-based metabolomics and lipidomics have been employed in large-scale biomedical research to discriminate infectious pathogens and uncover biomarkers associated with pathogenesis. PCR-MS has emerged as a new technology with the capability to directly identify known pathogens from the clinical specimens and the potential to identify genetic evidence of undiscovered pathogens. Moreover, miniaturized MS offers possible applications with relatively fast, highly sensitive, and potentially portable ways to analyze for viral compounds. However, beneficial aspects of these rapidly growing MS technologies in pandemics like COVID-19 outbreaks has been limited. Hence, this perspective gives a brief of the existing knowledge, current challenges, and opportunities for MS-based techniques as a promising avenue in studying emerging pathogen outbreaks such as COVID-19.