Nanovaccines against Viral Infectious Diseases.

Infectious diseases have always been regarded as one of the greatest global threats for the last century. The current ongoing COVID-19 pandemic caused by SARS-CoV-2 is living proof that the world is still threatened by emerging infectious diseases. Morbidity and mortality rates of diseases caused by Coronavirus have inflicted devastating social and economic outcomes. Undoubtedly, vaccination is the most effective method of eradicating infections and infectious diseases that have been eradicated by vaccinations, including Smallpox and Polio. To date, next-generation vaccine candidates with novel platforms are being approved for emergency use, such as the mRNA and viral vectored vaccines against SARS-CoV-2. Nanoparticle based vaccines are the perfect candidates as they demonstrated targeted antigen delivery, improved antigen presentation, and sustained antigen release while providing self-adjuvanting functions to stimulate potent immune responses. In this review, we discussed most of the recent nanovaccines that have found success in immunization and challenge studies in animal models in comparison with their naked vaccine counterparts. Nanovaccines that are currently in clinical trials are also reviewed.

Development of Next Generation Vaccines against SARS-CoV-2 and Variants of Concern.

SARS-CoV-2 has caused the COVID-19 pandemic, with over 673 million infections and 6.85 million deaths globally. Novel mRNA and viral-vectored vaccines were developed and licensed for global immunizations under emergency approval. They have demonstrated good safety and high protective efficacy against the SARS-CoV-2 Wuhan strain. However, the emergence of highly infectious and transmissible variants of concern (VOCs) such as Omicron was associated with considerable reductions in the protective efficacy of the current vaccines. The development of next-generation vaccines that could confer broad protection against both the SARS-CoV-2 Wuhan strain and VOCs is urgently needed. A bivalent mRNA vaccine encoding the Spike proteins of both the SARS-CoV-2 Wuhan strain and the Omicron variant has been constructed and approved by the US FDA. However, mRNA vaccines are associated with instability and require an extremely low temperature (-80 °C) for storage and transportation. They also require complex synthesis and multiple chromatographic purifications. Peptide-based next-generation vaccines could be developed by relying on in silico predictions to identify peptides specifying highly conserved B, CD4+ and CD8+ T cell epitopes to elicit broad and long-lasting immune protection. These epitopes were validated in animal models and in early phase clinical trials to demonstrate immunogenicity and safety. Next-generation peptide vaccine formulations could be developed to incorporate only naked peptides, but they are costly to synthesize and production would generate extensive chemical waste. Continual production of recombinant peptides specifying immunogenic B and T cell epitopes could be achieved in hosts such as E. coli or yeast. However, recombinant protein/peptide vaccines require purification before administration. The DNA vaccine might serve as the most effective next-generation vaccine for low-income countries, since it does not require an extremely low temperature for storage or need extensive chromatographic purification. The construction of recombinant plasmids carrying genes specifying highly conserved B and T cell epitopes meant that vaccine candidates representing highly conserved antigenic regions could be rapidly developed. Poor immunogenicity of DNA vaccines could be overcome by the incorporation of chemical or molecular adjuvants and the development of nanoparticles for effective delivery.

Antiviral peptides against SARS-CoV-2: therapeutic targets, mechanistic antiviral activity, and efficient delivery.

The global pandemic of COVID-19 is a serious public health concern. Over 625 million confirmed cases and more than 6 million deaths have been recorded worldwide. Although several vaccines and antiviral medications have been developed, their efficacy is limited by the emerging new SARS-CoV-2 strains. Peptide-based therapeutics is a fast-growing class of new drugs and have unique advantages over large proteins and small molecules. Antiviral peptides (AVPs) are short polycationic antivirals with broad-spectrum effects, which have been shown to exert both prophylactic and therapeutic actions against reported coronaviruses. The potential therapeutic targets of AVPs are located either on the virus (e.g., E-protein and S-protein) to prohibit viral binding or host cells, particularly, those present on the cell surface (e.g., ACE2 and TMPRSS2). Despite AVPs having promising antiviral effects, their efficacy is limited by low bioavailability. Thus, nanoformulation is a prerequisite for prolonged bioavailability and efficient delivery. This review aimed to present an insight into the therapeutic AVP targets on both virus and host cells by discussing their antiviral activities and associated molecular mechanisms. Besides, it described the technique for discovering and developing possible AVPs based on their targets, as well as the significance of using nanotechnology for their efficient delivery against SARS-CoV-2.

Development of virus-like particles-based vaccines against coronaviruses.

Severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the most impactful coronaviruses in human history, especially the latter, which brings revolutionary changes to human vaccinology. Due to its high infectivity, the virus spreads rapidly throughout the world and was declared a pandemic in March 2020. A vaccine would normally take more than 10 years to be developed. As such, there is no vaccine available for SARS-CoV and MERS-CoV. Currently, 10 vaccines have been approved for emergency use by World Health Organization (WHO) against SARS-CoV-2. Virus-like particle (VLP)s are nanoparticles resembling the native virus but devoid of the viral genome. Due to their self-adjuvanting properties, VLPs have been explored extensively for vaccine development. However, none of the approved vaccines against SARS-CoV-2 was based on VLP and only 4% of the vaccine candidates in clinical trials were based on VLPs. In the current review, we focused on discussing the major advances in the development of VLP-based vaccine candidates against the SARS-CoV, MERS-CoV, and SARS-CoV-2, including those in clinical and pre-clinical studies, to give a comprehensive overview of the VLP-based vaccines against the coronaviruses.

Identification of B-Cell Epitopes for Eliciting Neutralizing Antibodies against the SARS-CoV-2 Spike Protein through Bioinformatics and Monoclonal Antibody Targeting.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global public health crisis. Effective COVID-19 vaccines developed by Pfizer-BioNTech, Moderna, and Astra Zeneca have made significant impacts in controlling the COVID-19 burden, especially in reducing the transmission of SARS-CoV-2 and hospitalization incidences. In view of the emergence of new SARS-CoV-2 variants, vaccines developed against the Wuhan strain were less effective against the variants. Neutralizing antibodies produced by B cells are a critical component of adaptive immunity, particularly in neutralizing viruses by blocking virus attachment and entry into cells. Therefore, the identification of protective linear B-cell epitopes can guide epitope-based peptide designs. This study reviews the identification of SARS-CoV-2 B-cell epitopes within the spike, membrane and nucleocapsid proteins that can be incorporated as potent B-cell epitopes into peptide vaccine constructs. The bioinformatic approach offers a new in silico strategy for the mapping and identification of potential B-cell epitopes and, upon in vivo validation, would be useful for the rapid development of effective multi-epitope-based vaccines. Potent B-cell epitopes were identified from the analysis of three-dimensional structures of monoclonal antibodies in a complex with SARS-CoV-2 from literature mining. This review provides significant insights into the elicitation of potential neutralizing antibodies by potent B-cell epitopes, which could advance the development of multi-epitope peptide vaccines against SARS-CoV-2.

Immunogenicity and safety of SARS-CoV-2 vaccines in clinical trials.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were first detected in Wuhan, China in December 2019 and resulted in a worldwide pandemic in 2020. SARS-CoV-2 infections totalled more than 180 million with 3.9 million deaths as of June 24, 2021. Tremendous research efforts have resulted in the development of at least 64 vaccine candidates that have reached Phase I to III clinical trials within 14 months. The primary efficacy endpoint for a random placebo-controlled clinical trial of a COVID-19 vaccine to be approved by US FDA should confer at least 50% protection against COVID-19. Three COVID-19 vaccines (BNT162b2, mRNA-1273 and Sputnik V) in clinical Phase III trials have now achieved >90% efficacy in preventing COVID-19. Since SARS-CoV-2 is highly contagious, vaccines are expected to achieve at least 80% herd immunity in the world's population to effectively prevent SARS-CoV-2 infections. An overview of safety, immunogenicity and efficacy of the current frontrunner vaccines are reviewed.

Clinical Characteristics and Diagnostic Challenges of COVID-19: An Update From the Global Perspective.

Clinical characteristics are essential for the correct diagnosis of diseases. The current review aimed to summarize the global clinical characteristics of the COVID-19 patients systematically and identify their diagnostic challenges to help the medical practitioners properly diagnose and for better management of COVID-19 patients. We conducted a systematic search in PubMed, Web of Science, Scopus, Science Direct, and Google Scholar databases for original articles containing clinical information of COVID-19 published up to 7th May 2020. Two researchers independently searched the databases to extract eligible articles. A total of 34 studies from 8 different countries with 10889 case-patients were included for clinical characteristics. The most common clinical symptoms were cough 59.6, fever 46.9, fatigue 27.8, and dyspnea 20.23%. The prominent laboratory findings were lymphocytopenia 55.9, elevated levels of CRP 61.9, aspartate aminotransferase 53.3, LDH 40.8, ESR 72.99, serum ferritin 63, IL-6 52, and prothrombin time 35.47%, and decreased levels of platelets 17.26, eosinophils 59.0, hemoglobin 29, and albumin 38.4%. CT scan of the chest showed an abnormality in 93.50% cases with bilateral lungs 71.1%, ground-glass opacity 48%, lesion in lungs 78.3%, and enlargement of lymph node 50.7%. Common comorbidities were hypertension, diabetes, obesity, and cardiovascular diseases. The estimated median incubation period was 5.36 days, and the overall case fatality rate was 16.9% (Global case fatality outside China was 22.24%: USA 21.24%, Italy 25.61%, and others 0%; whereas the case fatality inside the Hubei Province of China was found to be 11.71%). Global features on the clinical characteristics of COVID-19 obtained from laboratory tests and CT scan results will provide useful information to the physicians to diagnose the disease and for better management of the patients as well as to address the diagnostic challenges to control the infection.

Development of multi-epitope peptide-based vaccines against SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic involving so far more than 22 million infections and 776,157 deaths. Effective vaccines are urgently needed to prevent SARS-CoV-2 infections. No vaccines have yet been approved for licensure by regulatory agencies. Even though host immune responses to SARS-CoV-2 infections are beginning to be unravelled, effective clearance of virus will depend on both humoral and cellular immunity. Additionally, the presence of Spike (S)-glycoprotein reactive CD4+ T-cells in the majority of convalescent patients is consistent with its significant role in stimulating B and CD8+ T-cells. The search for immunodominant epitopes relies on experimental evaluation of peptides representing the epitopes from overlapping peptide libraries which can be costly and labor-intensive. Recent advancements in B- and T-cell epitope predictions by bioinformatic analysis have led to epitope identifications. Assessing which peptide epitope can induce potent neutralizing antibodies and robust T-cell responses is a prerequisite for the selection of effective epitopes to be incorporated in peptide-based vaccines. This review discusses the roles of B- and T-cells in SARS-CoV-2 infections and experimental validations for the selection of B-, CD4+ and CD8+ T-cell epitopes which could lead to the construction of a multi-epitope peptide vaccine. Peptide-based vaccines are known for their low immunogenicity which could be overcome by incorporating immunostimulatory adjuvants and nanoparticles such as Poly Lactic-co-Glycolic Acid (PLGA) or chitosan.