The age-related dysregulation and decline of the immune system—collectively termed “immunosenescence”—has been generally associated with an increased susceptibility to infectious pathogens and poor vaccine responses in older adults. While numerous studies have reported on the clinical outcomes of infected or vaccinated individuals, our understanding of the mechanisms governing the onset of immunosenescence and its effects on adaptive immunity remains incomplete. Age-dependent differences in T and B lymphocyte populations and functions have been well-defined, yet studies that demonstrate direct associations between immune cell function and clinical outcomes in older individuals are lacking. Despite these knowledge gaps, research has progressed in the development of vaccine and adjuvant formulations tailored for older adults in order to boost protective immunity and overcome immunosenescence. In this review, we will discuss the development of vaccines for older adults in light of our current understanding—or lack thereof—of the aging immune system. We highlight the functional changes that are known to occur in the adaptive immune system with age, followed by a discussion of current, clinically relevant pathogens that disproportionately affect older adults and are the central focus of vaccine research efforts for the aging population. We conclude with an outlook on personalized vaccine development for older adults and areas in need of further study in order to improve our fundamental understanding of adaptive immunosenescence.

This article provides a review of studies evaluating the role of host (and viral) genetics (including variation in HLA genes) in the immune response to coronaviruses, as well as the clinical outcome of coronavirus‐mediated disease. The initial sections focus on seasonal coronaviruses, SARS‐CoV, and MERS‐CoV. We then examine the state of the knowledge regarding genetic polymorphisms and SARS‐CoV‐2 and COVID‐19. The article concludes by discussing research areas with current knowledge gaps and proposes several avenues for future scientific exploration in order to develop new insights into the immunology of SARS‐CoV‐2.

In the midst of the severe acute respiratory syndrome coronavirus 2 pandemic and its attendant morbidity and mortality, safe and efficacious vaccines are needed that induce protective and long-lived immune responses. More than 120 vaccine candidates worldwide are in various preclinical and phase 1 to 3 clinical trials that include inactivated, live-attenuated, viral-vectored replicating and nonreplicating, protein-and peptide-based, and nucleic acid approaches. Vaccines will be necessary both for individual protection and for the safe development of population-level herd immunity. Publicprivate partnership collaborative efforts, such as the Accelerating COVID-19 Therapeutic Interventions and Vaccines mechanism, are key to rapidly identifying safe and effective vaccine candidates as quickly and efficiently as possible. In this article, we review the major vaccine approaches being taken and issues that must be resolved in the quest for vaccines to prevent coronavirus disease 2019. For this study, we scanned the PubMed database from 1963 to 2020 for all publications using the following search terms in various combinations: SARS, MERS, COVID-19, SARS-CoV-2, vaccine, clinical trial, coronavirus, pandemic, and vaccine development. We also did a Web search for these same terms. In addition, we examined the World Health Organization, Centers for Disease Control and Prevention, and other public health authority websites. We excluded abstracts and all articles that were not written in English.

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A novel coronavirus (SARS-CoV-2) emerged from China in late 2019 and rapidly spread across the globe, infecting millions of people and generating societal disruption on a level not seen since the 1918 influenza pandemic. A safe and effective vaccine is desperately needed to prevent the continued spread of SARS-CoV-2; yet, rational vaccine design efforts are currently hampered by the lack of knowledge regarding viral epitopes targeted during an immune response, and the need for more in-depth knowledge on betacoronavirus immunology. to that end, we developed a computational workflow using a series of open-source algorithms and webtools to analyze the proteome of SARS-CoV-2 and identify putative T cell and B cell epitopes. Utilizing a set of stringent selection criteria to filter peptide epitopes, we identified 41 T cell epitopes (5 HLA class I, 36 HLA class II) and 6 B cell epitopes that could serve as promising targets for peptide-based vaccine development against this emerging global pathogen. To our knowledge, this is the first study to comprehensively analyze all 10 (structural, non-structural and accessory) proteins from SARS-CoV-2 using predictive algorithms to identify potential targets for vaccine development. In December 2019, public health officials in Wuhan, China, reported the first case of severe respiratory disease attributed to infection with the novel coronavirus SARS-CoV-2 1. Since its emergence, SARS-CoV-2 has spread rapidly via human-to-human transmission 2 , threatening to overwhelm healthcare systems around the world and resulting in the declaration of a pandemic by the World Health Organization 3. The disease caused by the virus (COVID-19) is characterized by fever, pneumonia, and other respiratory and inflammatory symptoms that can result in severe inflammation of lung tissue and ultimately death-particularly among older adults or individuals with underlying comorbidities 4-6. As of this writing, the SARS-CoV-2 pandemic has resulted in 4 million confirmed cases of COVID-19 and over 280,000 deaths worldwide 7. SARS-CoV-2 is the third pathogenic coronavirus to cross the species barrier into humans in the past two decades, preceded by severe acute respiratory syndrome coronavirus (SARS-CoV) 8,9 and Middle-East respiratory syndrome coronavirus (MERS-CoV) 10. All three of these viruses belong to the β-coronavirus genus and have either been confirmed (SARS-CoV) or suggested (MERS-CoV, SARS-CoV-2) to originate in bats, with transmission to humans occurring through intermediary animal hosts 11-14. While previous zoonotic spillovers of coronaviruses have been marked by high case fatality rates (~ 10% for SARS-CoV; ~ 34% for MERS-CoV), widespread transmission of disease has been relatively limited (8,098 cases of SARS; 2,494 cases of MERS) 15. In contrast, SARS-CoV-2 is estimated to have a lower case fatality rate (~ 2 to 4%) but is far more infectious and has achieved worldwide spread in a matter of months 16. As the number of COVID-19 cases continues to grow, there is an urgent need for a safe and ef...

Heptamethine cyanines are broadly used for a range of near-infrared imaging applications. As with many fluorophores, these molecules are prone to forming nonemissive aggregates upon biomolecule conjugation. Prior work has focused on persulfonation strategies, which only partially address these issues. Here, we report a new set of peripheral substituents, short polyethylene glycol chains on the indolenine nitrogens and a substituted alkyl ether at the C4′ position, that provide exceptionally aggregation-resistant fluorophores. These symmetrical molecules are net-neutral, can be prepared in a concise sequence, and exhibit no evidence of H-aggregation even at high labeling density when appended to monoclonal antibodies or virus-like particles. The resulting fluorophore–biomolecule conjugates exhibit exceptionally bright in vitro and in vivo signals when compared to a conventional persulfonated heptamethine cyanine. Overall, these efforts provide a new class of heptamethine cyanines with significant utility for complex labeling applications.

28A novel coronavirus (SARS-CoV-2) emerged from China in late 2019 and rapidly spread across 29 the globe, infecting millions of people and generating societal disruption on a level not seen since the 30 1918 influenza pandemic. A safe and effective vaccine is desperately needed to prevent the continued 31 spread of SARS-CoV-2; yet, rational vaccine design efforts are currently hampered by the lack of 32 knowledge regarding viral epitopes targeted during an immune response, and the need for more in-depth 33 knowledge on betacoronavirus immunology. To that end, we developed a computational workflow using 34a series of open-source algorithms and webtools to analyze the proteome of SARS-CoV-2 and identify 35 putative T cell and B cell epitopes. Using increasingly stringent selection criteria to select peptides with 36 significant HLA promiscuity and predicted antigenicity, we identified 41 potential T cell epitopes (5 HLA 37 class I, 36 HLA class II) and 6 potential B cell epitopes, respectively. Docking analysis and binding 38 predictions demonstrated enrichment for peptide binding to HLA-B (class I) and HLA-DRB1 (class II) 39 molecules. Overlays of predicted B cell epitopes with the structure of the viral spike (S) glycoprotein 40 revealed that 4 of 6 epitopes were located in the receptor-binding domain of the S protein. To our 41 knowledge, this is the first study to comprehensively analyze all 10 (structural, non-structural and 42 accessory) proteins from SARS-CoV-2 using predictive algorithms to identify potential targets for 43 vaccine development. 44 Significance Statement: 47The novel coronavirus SARS-CoV-2 recently emerged from China, rapidly spreading and ushering in a 48 global pandemic. Despite intensive research efforts, our knowledge of SARS-CoV-2 immunology and the 49 proteins targeted by the immune response remains relatively limited, making it difficult to rationally 50 design candidate vaccines. We employed a suite of bioinformatic tools, computational algorithms, and 51 structural modeling to comprehensively analyze the entire SARS-CoV-2 proteome for potential T cell and 52 B cell epitopes. Utilizing a set of stringent selection criteria to filter peptide epitopes, we identified 41 T 53 cell epitopes (5 HLA class I, 36 HLA class II) and 6 B cell epitopes that could serve as promising targets 54 for peptide-based vaccine development against this emerging global pathogen. 55 56 57 58 157

Near-IR fluorescent Qβ virus-like particles (VLPs) were produced in a high yield by packaging highly red-shifted monomeric and dimeric versions of biliverdin-dependent fluorescent proteins within the capsid shell. The simple addition of biliverdin hydrochloride to the medium during or after Escherichia coli protein expression was enough to produce fully matured encapsidated fluorophores. The packaged near-IR proteins exhibited identical photochemical properties to their nonencapsidated analogues but were far more stable toward heat, chaotropeinduced denaturation, and proteolysis. Noninvasive in vivo imaging showed the VLPs to traffic primarily to the liver after systemic injection in mice, revealing that the particles were easily detected by a standard instrument. ■ MATERIALS AND METHODSCloning, Production, and Purification of Qβ-Packaged NIR FPs. Bicistronic plasmids coding for co-expression of both Qβ CP and