Nucleic acid vaccine candidates encapsulated with mesoporous silica nanoparticles against MERS-CoV.

Middle East respiratory coronavirus (MERS-CoV) is a newly emergent, highly pathogenic coronavirus that is associated with 34% mortality rate. MERS-CoV remains listed as priority pathogen by the WHO. Since its discovery in 2012 and despite the efforts to develop coronaviruses vaccines to fight against SARS-CoV-2, there are currently no MERS-CoV vaccine that has been approved. Therefore, there is high demand to continue on the development of prophylactic vaccines against MERS-CoV. Current advancements in vaccine developments can be adapted for the development of improved MERS-CoV vaccines candidates. Nucleic acid-based vaccines, including pDNA and mRNA, are relatively new class of vaccine platforms. In this work, we developed pDNA and mRNA vaccine candidates expressing S.FL gene of MERS-CoV. Further, we synthesized a silane functionalized hierarchical aluminosilicate to encapsulate each vaccine candidates. We tested the nucleic acid vaccine candidates in mice and evaluated humoral antibodies response. Interestingly, we determined that the non-encapsulated, codon optimized S.FL pDNA vaccine candidate elicited the highest level of antibody responses against S.FL and S1 of MERS-CoV. Encapsulation of mRNA with nanoporous aluminosilicate increased the humoral antibody responses, whereas encapsulation of pDNA did not. These findings suggests that MERS-CoV S.FL pDNA vaccine candidate induced the highest level of humoral responses. This study will enhance further optimization of nanosilica as potential carrier for mRNA vaccines. In conclusion, this study suggests MERS-CoV pDNA vaccine candidate as a suitable vaccine platform for further pivotal preclinical testings.

hCoronavirusesDB: an integrated bioinformatics resource for human coronaviruses.

In the twenty-first century, three new human coronaviruses have been identified with known zoonotic origins: severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, and Middle East respiratory syndrome coronavirus (MERS-CoV). SARS-CoV-2 was identified in November 2019 and is associated with an ongoing pandemic. Molecular surveillance and monitoring studies are essential for containing viral outbreaks, epidemics, and pandemics. In addition, the development and deployment of bioinformatics resources for highly pathogenic human coronaviruses are crucial for understanding the genetic and immunogenic landscape associated with these viruses. Here, we introduce an open-access, integrated resource for SARS-CoV, SARS-CoV-2, and MERS-CoV: the Human Coronaviruses Database and Analysis Resource (hCoronavirusesDB; http://hcoronaviruses.net/), which include nucleotide and protein sequence data obtained for these viruses. The database also offers a user-friendly search interface coupled with bioinformatics analytics and visualization tools. In addition, hCoronavirusesDB contains curated, experimentally validated B cell and T cell epitope data for these viruses. This resource can assist with the molecular surveillance necessary to trace virus circulation and contribute to microevolutionary studies. This application can also serve as a valuable resource for the development of rationally designed pan-coronavirus diagnostic tools, vaccines, and therapeutic agents. Database URL:http://hcoronaviruses.net/.

Immunogenicity of Multiple Doses of pDNA Vaccines against SARS-CoV-2.

Since its identification in Wuhan, China, in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has resulted in 46 million cases and more than one million deaths worldwide, as of 30 October 2020. Limited data exist on the magnitude and durability of antibodies generated by natural infection with SARS-CoV-2 and whether they can provide long-lasting immunity from reinfection. Vaccination has proven the most effective measure for controlling and preventing pandemics and, thus, development of a vaccine against COVID-19 is a top priority. However, the doses required to induce effective, long-lasting antibody responses against SARS-CoV-2 remain undetermined. Here, we present the development of SARS-CoV-2 vaccine candidates encoding the viral spike (S) gene, generated using plasmid (p)DNA technology, and we demonstrate the eliciting of S-specific antibodies in mice after three and four doses. The magnitude of binding and neutralizing antibody responses with three doses of synthetic, codon-optimized, full-length S (S.opt.FL) vaccine is comparable to that generated after four doses, suggesting that three doses are sufficient to elicit robust immune responses. Conversely, four doses of S1.opt pDNA vaccine, containing the S globular head, are required to elicit high levels of neutralizing antibodies. Furthermore, the S.opt.FL pDNA vaccine induces the highest serum levels of interferon (IFN)-γ, a marker for activation of cellular immune responses. Overall, our data show that three doses of S.FL pDNA vaccine elicit potent neutralizing antibody responses, with preclinical data that support the immunogenicity of these COVID-19 vaccine candidates and provide justification for further translational studies.

Mumps Vaccines: Current Challenges and Future Prospects.

Five decades have passed since the first mumps vaccine was licensed. Over this period, a resurgence of mumps infections has been recorded worldwide. Although global mumps infections have been controlled through vaccination, outbreaks are still on the rise, including in populations with high vaccination coverage. Several epidemiological studies suggest that this infectious virus continues to be a worldwide public health threat. The development and deployment of an improved, prophylactic mumps vaccine that provides long-lasting protection is indeed a priority. The purpose of this review is to provide an immuno-biological perspective on mumps vaccines. Here, we review the virology of mumps, licensed mumps vaccines, and the typical immune responses elicited following mumps vaccination. Furthermore, we discuss the limitations and challenges of the currently licensed mumps vaccines and provide strategies for the development of an improved mumps vaccine.

Quantum dots encapsulated with curcumin inhibit the growth of colon cancer, breast cancer and bacterial cells.

Aim: To synthesize and examine the impact of free Eudragit® RS 100 nanoparticles (LN01), Quantum dots curcumin-loaded Eudragit RS 100 nanoparticles (LN04), and un-encapsulated curcumin nanoparticles (LN06) on cancerous and bacterial cells. Materials & methods: The LN01, LN04, LN06 were synthesized and characterized by Fourier transform infrared, ζ potential, UV-Vis spectroscopy, transmission electron microscopy and scanning electron microscopy and their biological activities were evaluated. Results: LN04 profoundly inhibited the growth of colon (HCT-116) cancerous cells (10.64% cell viability) and breast cancer (MCF-7) cells (10.32% cell viability) with compared to LN01 and LN06. Normal cells (HEK-293) did not show any inhibition after treatments. In addition, LN04 show better inhibitory action on bacterial growth compared with LN01 and LN06. Conclusion: We suggest that LN04 selectively target cancerous and bacterial cells and therefore possess potential anticancer and antibacterial capabilities.

IRAM: virus capsid database and analysis resource.

IRAM is an online, open access, comprehensive database and analysis resource for virus capsids. The database includes over 200 000 hierarchically organized capsid-associated nucleotide and amino acid sequences, as well as 193 capsids structures of high resolution (1-5 Å). Each capsid's structure includes a data file for capsid domain (PDB), capsid symmetry unit (PDB) and capsid structure information (PSF); these contain capsid structural information that is necessary to run further computational studies. Physicochemical properties analysis is implemented for calculating capsid total charge at given radii and for calculating charge distributions. This resource includes BLASTn and BLASTp tools, which can be applied to compare nucleotide and amino acid sequences. The diverse functionality of IRAM is valuable to researchers because it integrates different aspects of virus capsids via a user-friendly interface. Such data are critical for studying capsid evolution and patterns of conservation. The IRAM database can also provide initial necessary information for the design of synthetic capsids for various biotechnological applications.

MMRdb: Measles, mumps, and rubella viruses database and analysis resource.

Measles, mumps, and rubella viruses are well known human pathogens that cause mild to severe illnesses. Despite the existence of MMR vaccines since 1971, outbreaks have been largely documented even in highly vaccinated populations. There is a pressing need to develop a resource to monitor genetic and antigenic variations among these viruses. Here, we introduced MMRdb, a web central database and analysis resource for measles, mumps, and rubella viruses. Users can search viruses at gene level and obtain sequence information based on gene product, geographic location, year, or host. The MMRdb also catalogs experimentally verified B cells and T cells antigenic epitopes data. A set of computation tools such as multiple sequence alignment, Geo Chart, and sequence similarity BLAST search has been implemented in a user-friendly database. The main features of this database will assist researchers in monitoring genetics and antigenic variations, tracking geographic spread with regards of sequence information, and facilitate the development of diagnostics, vaccines, and immunotherapeutics. Database URL: http://mmrdb.org.

Large-scale analysis of B-cell epitopes of envelope: Implications for Zika vaccine and immunotherapeutic development.

Background: Cases of the re-emergence of Zika virus in 2015 were associated with severe neurologic complications, including Gillien-Barre syndrome in adults and congenital Zika syndrome in newborns. The major structural determinant of immunity to the Zika virus is the E protein. Although B-cell epitopes of Zika E protein were recently identified, data regarding epitope variations among Zika strains in pre-epidemic and epidemic periods are lacking. Methods: Here, we conducted systematic bioinformatics analyses of Zika strains isolated between 1968 and 2017. Multiple sequence alignment of E protein as well as B-cell epitopes annotations were performed. In addition, homology-based approach was utilized to construct three-dimensional structures of monomeric E glycoproteins to annotate epitope variations. Lastly, of N-glycosylation patterns and prediction of protein stability upon mutations were also investigated. Results: Our analyses indicates that epitopes recognized by human mAbs ZIKV-117, ZIKV-15, and ZIKV-119 were highly conserved, suggesting as attractive targets for the development of vaccines and immunotherapeutics directed against diverse Zika strains. In addition, the epitope recognized by ZIKV-E-2A10G6 mAb derived from immunized mice was highly conserved across Zika strains. Conclusions: Our data provide new insights regarding antigenic similarities between Zika strains circulating worldwide. These data are essential for understanding the impact of evolution on antigenic cross-reactivity between Zika lineages and strains. Further in-vitro analyses are needed to determine how mutations could impact the development of vaccines that can effectively neutralize Zika viruses.

Cross reactivity of serum antibody responses elicited by DNA vaccines expressing HA antigens from H1N1 subtype influenza vaccines in the past 30 years.

In the past three decades, ten H1 subtype influenza vaccines have been recommended for global seasonal flu vaccination. Some of them were used only for one year before being replaced by another H1 flu vaccine while others may be used for up to seven years. While the selection of a new seasonal flu vaccine was based on the escape of a new emerging virus that was not effectively protected by the existing flu formulation, there is limited information on the magnitude and breadth of cross reactivity among H1 subtype virus circulation over a long period. In the current study, HA-expressing DNA vaccines were constructed to express individual HA antigens from H1 subtype vaccines used in the past 30 y. Rabbits naïve to HA antibody responses were immunized with these HA DNA vaccines and the cross reactivity of these sera against HA antigen and related H1 viruses in the same period was studied. Our data indicate that the level of cross reactivity was different for different viral isolates and the key mutations responsible for the cross reactivity may involve only a limited number of residues. Our results provide useful information for the development of improved seasonal vaccines than can achieve broad protection against viruses within the same H1 subtype.