Nanoparticle-based Vaccine Research Articles

Polymeric nanoparticle-based nanovaccines for cancer immunotherapy.

Therapeutic cancer vaccines, which are designed to amplify tumor-specific T cell responses, have been envisioned as one of the most powerful tools for effective cancer immunotherapy. However, increasing the potency, quality and durability of the vaccine response remains a big challenge. In recent years, materials-based delivery systems focusing on the co-delivery of antigens and adjuvants to enhance cancer vaccination therapy have attracted increasing interest. Among various materials, polymeric nanoparticles (NPs) with different physicochemical properties which can incorporate multiple immunological cues are of great interest. In this review, the recent progress in the design and construction of both ex vivo subunit and in situ cancer vaccines using polymeric NPs is summarized. Especially, we will focus on how these NPs improve the adjuvanticity of vaccines. The design principles of polymeric NPs for ex vivo subunit cancer vaccines and in situ cancer vaccination are also discussed. Finally, we want to briefly discuss molecular chaperones in cancer immunity and the applications of our unique self-assembly mixed shell polymeric micelle-based nanochaperones for cancer vaccines.

Nanoparticle vaccines can be designed to induce pDC support of mDCs for increased antigen display.

Cancer vaccine immunotherapy facilitates the immune system's recognition of tumor-associated antigens, and the biomolecular design of these vaccines using nanoparticles is one important approach towards obtaining strong anti-tumor responses. Following activation of dendritic cells (DCs), a robust CD8+ T cell-mediated adaptive immune response is critical for tumor elimination. While the role of efficient antigen-presenting myeloid DCs (mDCs) is conventionally attributed towards vaccine efficacy, participation by highly cytokine-producing plasmacytoid DCs (pDCs) is less understood and is often overlooked. We examined vaccines based on the E2 protein nanoparticle platform that delivered encapsulated TLR9 agonist bacterial-like DNA (CpG1826 or CpG1018) or TLR7 agonist viral ssRNA to determine their efficacy over free agonists in activating both mDCs and pDCs for antigen presentation. Although mDCs were only activated by nanoparticle-encapsulated TLR9 agonists, pDCs were activated by all the individually tested constructs, and CpG1826 was shown to induce pDC cytokine production. Transfer of secreted factors from pDCs that were stimulated with a vaccine formulation comprising peptide antigen and CpG1826 enhanced mDC display of the antigen, particularly when delivered in nanoparticles. Only when treated with nanoparticle-conjugated vaccine could pDCs secrete factors to induce antigen display on naïve mDCs. These results reveal that pDCs can aid mDCs, highlighting the importance of activating both pDCs and mDCs in designing effective cancer vaccines, and demonstrate the advantage of using nanoparticle-based vaccine delivery.

Instigation of the epoch of nanovaccines in cancer immunotherapy.

Cancer is an unprecedented proliferation of cells leading to abnormalities in differentiation and maturation. Treatment of primary and metastatic cancer is challenging. In addition to surgery, chemotherapy and radiation therapies have been conventionally used; however, they suffer from severe toxicity and non-specificity. Immunotherapy, the science of programming the body's own defense system against cancer has gained tremendous attention in the last few decades. However, partial immunogenic stimulation, premature degradation and inability to activate dendritic and helper T cells has resulted in limited clinical success. The era of nanomedicine has brought about several breakthroughs in various pharmaceutical and biomedical fields. Hereby, we review and discuss the interplay of tumor microenvironment (TME) and the immunological cascade and how they can be employed to develop nanoparticle-based cancer vaccines and immunotherapies. Nanoparticles composed of lipids, polymers and inorganic materials contain useful properties suitable for vaccine development. Proteinaceous vaccines derived from mammalian viruses, bacteriophages and plant viruses also have unique advantages due to their immunomodulation capabilities. This review accounts for all such considerations. Additionally, we explore how attributes of nanotechnology can be utilized to develop successful nanomedicine-based vaccines for cancer therapy. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Nanomaterials-based vaccines to target intracellular bacterial pathogens.

Development of novel immunization approaches to combat a growing list of emerging and ancient infectious agents is a global health priority. Intensive efforts over the last several decades have identified alternative approaches to improve upon traditional vaccines that are based on live, attenuated agents, or formulations of inactivated agents with adjuvants. Rapid advances in RNA-based and other delivery systems for immunization have recently revolutionized the potential to protect populations from viral pathogens, such as SARS-CoV-2. Similar efforts to combat bacterial pathogens, especially species with an intracellular niche, have lagged significantly. In the past decade, advances in nanotechnology have yielded a variety of new antigen/adjuvant carrier systems for use in vaccine development against infectious viruses and bacteria. The tunable properties of nanomaterial-based vaccines allow for balancing immunogenicity and safety which is a key hurdle in traditional antigen and adjuvant formulations. In this review, we discuss several novel nanoparticle-based vaccine platforms that show promise for use against intracellular bacteria as demonstrated by the feasibility of construction, enhanced antigen presentation, induction of cell mediated and humoral immune responses, and improved survival outcomes in in vivo models.

Nanoparticle-Based Bivalent Swine Influenza Virus Vaccine Induces Enhanced Immunity and Effective Protection against Drifted H1N1 and H3N2 Viruses in Mice.

Swine influenza virus (SIV) circulates worldwide, posing substantial economic loss and disease burden to humans and animals. Vaccination remains the most effective way to prevent SIV infection and transmission. In this study, we evaluated the protective efficacy of a recombinant, baculovirus-insect cell system-expressed bivalent nanoparticle SIV vaccine in mice challenged with drifted swine influenza H1N1 and H3N2 viruses. After a prime-boost immunization, the bivalent nanoparticle vaccine (BNV) induced high levels of hemagglutination inhibition (HAI) antibodies, virus-neutralization (VN) antibodies, and antigen-specific IgG antibodies in mice, as well as more efficient cytokine levels. The MF59 and CPG1 adjuvant could significantly promote both humoral and cellular immunity of BNV. The MF59 adjuvant showed a balanced Th1/Th2 immune response, and the CPG1 adjuvant tended to show a Th1-favored response. The BALB/c challenge test showed that BNV could significantly reduce lung viral loads and feces viral shedding, and showed fewer lung pathological lesions than those in PBS and inactivated vaccine groups. These results suggest that this novel bivalent nanoparticle swine influenza vaccine can be used as an efficacious vaccine candidate to induce robust immunity and provide broad protection against drifted subtypes in mice. Immune efficacy in pigs needs to be further evaluated.

An ambient-temperature stable nanoparticle-based vaccine for nasal application that confers long-lasting immunogenicity to carried antigens.

Polyhedrins are viral proteins present in a large family of baculoviruses that form occlusion bodies (polyhedra). These structures protect the virus particles from the outside environment until they are ingested by susceptible insects. Occluded viruses can sustain inclement weather for long periods of time. Therefore, the polyhedra is a natural preservative that keeps the viral structure intact at ambient temperature for years. In a previous study we identified the first 110 amino acids from polyhedrin (PH(1-110)) as a good candidate to carry antigens of interest. As a proof of concept, we produced a fusion protein with PH(1-110) and the green fluorescent protein (PH(1-110)GFP). The fusion protein associates spontaneously during its synthesis resulting in the formation of nanoparticles. Nasal immunization with these nanoparticles and in the absence of any adjuvant, results in a robust immune response with the production of IgG immunoglobulins that remained elevated for months and that selectively recognize the GFP but not PH(1-110). These results indicate that PH(1-110) is poorly immunogenic but capable of enhancing the immune response to GFP.

Nanovaccines to combat virus-related diseases.

The invention and application of vaccines have made tremendous contributions to fight against pandemics for human beings. However, current vaccines still have shortcomings such as insufficient cellular immunity, the lack of cross-protection, and the risk of antibody-dependent enhancement (ADE). Thus, the prevention and control of pandemic viruses including Ebola Virus, human immunodeficiency virus (HIV), Influenza A viruses, Zika, and current SARS-CoV-2 are still extremely challenging. Nanoparticles with unique physical, chemical, and biological properties, hold promising potentials for the development of ideal vaccines against these viral infections. Moreover, the approval of the first nanoparticle-based mRNA vaccine BNT162b has established historic milestones that greatly inspired the clinical translation of nanovaccines. Given the safety and extensive application of subunit vaccines, and the rapid rise of mRNA vaccines, this review mainly focuses on these two vaccine strategies and provides an overview of the nanoparticle-based vaccine delivery platforms to tackle the current and next global health challenges. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Role of Nanomaterials in COVID-19 Prevention, Diagnostics, Therapeutics, and Vaccine Development

Facing the deadly pandemic caused by the SARS-CoV-2 virus all over the globe, it is crucial to devote efforts to fighting and preventing this infectious virus. Nanomaterials have gained much attention after the approval of lipid nanoparticle-based COVID-19 vaccines by the United States Food and Drug Administration (USFDA). In light of increasing demands for utilizing nanomaterials in the management of COVID-19, this comprehensive review focuses on the role of nanomaterials in the prevention, diagnostics, therapeutics, and vaccine development of COVID-19. First, we highlight the variety of nanomaterials usage in the prevention of COVID-19. We discuss the advantages of nanomaterials as well as their uses in the production of diagnostic tools and treatment methods. Finally, we review the role of nanomaterials in COVID-19 vaccine development. This review offers direction for creating products based on nanomaterials to combat COVID-19.

Understanding and combating COVID-19 using the biology and chemistry of SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Symptoms of COVID-19 can range from asymptomatic to severe, which could lead to fatality. Like other pathogenic viruses, the infection of SARS-CoV-2 relies on binding its spike glycoprotein to the host receptor angiotensin-converting enzyme 2 (ACE 2). Molecular studies suggested that there is a high affinity between the spike glycoprotein and ACE 2 that might arise due to their hydrophobic interaction. This property is mainly responsible for making this virus highly infectious. Apart from this, the transmissibility of the virus, prolonged viability in certain circumstances, and rapid mutations also contributed to the current pandemic situation. Nanotechnology provides potential alternative solutions to combat COVID-19 with the development of i. nanomaterial-based COVID-19 detection technology, ii. nanomaterial-based disinfectants, iii. nanoparticle-based vaccines, and iv. nanoparticle-based drug delivery. Hence, this review provides diverse insight into understanding COVID-19.

Lipid nanoparticle-based mRNA vaccines in cancers: Current advances and future prospects

Messenger RNA (mRNA) vaccines constitute an emerging therapeutic method with the advantages of high safety and efficiency as well as easy synthesis; thus, they have been widely used in various human diseases, especially in malignant cancers. However, the mRNA vaccine technology has some limitations, such as instability and low transitive efficiency in vivo, which greatly restrict its application. The development of nanotechnology in the biomedical field offers new strategies and prospects for the early diagnosis and treatment of human cancers. Recent studies have demonstrated that Lipid nanoparticle (LNP)-based mRNA vaccines can address the poor preservation and targeted inaccuracy of mRNA vaccines. As an emerging cancer therapy, mRNA vaccines potentially have broad future applications. Unlike other treatments, cancer mRNA vaccines provide specific, safe, and tolerable treatments. Preclinical studies have used personalized vaccines to demonstrate the anti-tumor effect of mRNA vaccines in the treatment of various solid tumors, including colorectal and lung cancer, using these in a new era of therapeutic cancer vaccines. In this review, we have summarized the latest applications and progress of LNP-based mRNA vaccines in cancers, and discussed the prospects and limitations of these fields, thereby providing novel strategies for the targeted therapy of cancers.

Vaccination with a structure-based stabilized version of malarial antigen Pfs48/45 elicits ultra-potent transmission-blocking antibody responses

SummaryMalaria transmission-blocking vaccines (TBVs) aim to elicit human antibodies that inhibit sporogonic development of Plasmodium falciparum in mosquitoes, thereby preventing onward transmission. Pfs48/45 is a leading clinical TBV candidate antigen and is recognized by the most potent transmission-blocking monoclonal antibody (mAb) yet described; still, clinical development of Pfs48/45 antigens has been hindered, largely by its poor biochemical characteristics. Here, we used structure-based computational approaches to design Pfs48/45 antigens stabilized in the conformation recognized by the most potently inhibitory mAb, achieving >25°C higher thermostability compared with the wild-type protein. Antibodies elicited in mice immunized with these engineered antigens displayed on liposome-based or protein nanoparticle-based vaccine platforms exhibited 1–2 orders of magnitude superior transmission-reducing activity, compared with immunogens bearing the wild-type antigen, driven by improved antibody quality. Our data provide the founding principles for using molecular stabilization solely from antibody structure-function information to drive improved immune responses against a parasitic vaccine target.

Monitoring Anti-PEG Antibodies Level upon Repeated Lipid Nanoparticle-Based COVID-19 Vaccine Administration.

PEGylated lipids are one of the four constituents of lipid nanoparticle mRNA COVID-19 vaccines. Therefore, various concerns have been raised on the generation of anti-PEG antibodies and their potential role in inducing hypersensitivity reactions following vaccination or in reducing vaccine efficacy due to anti-carrier immunity. Here, we assess the prevalence of anti-PEG antibodies, in a cohort of vaccinated individuals, and give an overview of their time evolution after repeated vaccine administrations. Results indicate that, in our cohort, the presence of PEG in the formulation did not influence the level of anti-Spike antibodies generated upon vaccination and was not related to any reported, serious adverse effects. The time-course analysis of anti-PEG IgG showed no significant booster effect after each dose, whereas for IgM a significant increase in antibody levels was detected after the first and third dose. Data suggest that the presence of PEG in the formulation does not affect safety or efficacy of lipid-nanoparticle-based COVID-19 vaccines.

A nanoparticle-based COVID-19 vaccine candidate elicits broad neutralizing antibodies and protects against SARS-CoV-2 infection

A vaccine candidate to SARS-CoV-2 was constructed by coupling the viral receptor binding domain (RBD) to the surface of the papaya mosaic virus (PapMV) nanoparticle (nano) to generate the RBD-PapMV vaccine. Immunization of mice with the coupled RBD-PapMV vaccine enhanced the antibody titers and the T-cell mediated immune response directed to the RBD antigen as compared to immunization with the non-coupled vaccine formulation (RBD + PapMV nano). Anti-RBD antibodies, generated in vaccinated animals, neutralized SARS-CoV-2 infection in vitro against the ancestral, Delta and the Omicron variants. At last, immunization of mice susceptible to the infection by SARS-CoV-2 (K18-hACE2 transgenic mice) with the RBD-PapMV vaccine induced protection to the ancestral SARS-CoV-2 infectious challenge. The induction of the broad neutralization against SARS-CoV-2 variants induced by the RBD-PapMV vaccine demonstrate the potential of the PapMV vaccine platform in the development of efficient vaccines against viral respiratory infections.

A mRNA Vaccine Encoding for a RBD 60-mer Nanoparticle Elicits Neutralizing Antibodies and Protective Immunity Against the SARS-CoV-2 Delta Variant in Transgenic K18-hACE2 Mice.

Two years into the COVID-19 pandemic there is still a need for vaccines to effectively control the spread of novel SARS-CoV-2 variants and associated cases of severe disease. Here we report a messenger RNA vaccine directly encoding for a nanoparticle displaying 60 receptor binding domains (RBDs) of SARS-CoV-2 that acts as a highly effective antigen. A construct encoding the RBD of the Delta variant elicits robust neutralizing antibody response, and also provides protective immunity against the Delta variant in a widely used transgenic mouse model. We ultimately find that the proposed mRNA RBD nanoparticle-based vaccine provides a flexible platform for rapid development and will likely be of great value in combatting current and future SARS-CoV-2 variants of concern.

State of the Art Nanotechnology to Combat Current COVID-19 Outbreak

COVID-19 has lately emerged as the most severe pandemics of the 20 century, with lethal consequences and ahigher rate of propagation. More than 6.3 million individuals have died around the world as of this writing (June 10, 2022), while around 11.9 billion people have been vaccinated worldwide by June 06, 2022.1 Since noeffective drug against COVID-19 has been approved to date, it highlights the crucial need for developing newertherapeutic targets, vaccines, and antibodies to eliminate COVID-19 viral load and associated side effects.2Though, delivering these agents in a tailored manner that avoids off-targeting and excessive drug absorption isextremely difficult. It is commonly known that nanotechnology-based drug delivery systems improveconventional therapies, up till now, their application in viral infections remains underdeveloped andunderutilized, as seen by the COVID-19 epidemic.3 Nanotechnology enhances the pharmacological propertiesof drug by allowing the use of nano-systems such as organic (micelles, liposomes, polymers) and inorganic(metallic, quantum dots, carbon nano-tubes) nanoparticles for encapsulation. Nanotechnology has the highpotential to combat against COVID-19 in a number of ways, for instance, prevention of viral contamination byspraying and developing personal protective equipment (PPE), as well as developing appropriate antiviraldisinfectants.4 Numerous nanocarriers have been used for drug delivery to address issues such as inadequatesolubility, permeability, and target ability, all of which contribute to drug molecules failing to exert the desiredtherapeutic impact.5 To identify COVID-19 infection or immune response, various nanomaterials can beemployed as extremely accurate and sensitive nano-based biosensors.6 A nanotechnology research group atUniversity of Georgia developed a rapid test based on optical sensors designed for COVID-19 detection inAugust 2020. In March 2022, they filed a patent application on rapid COVID-19 detection, using an optical nanosensor, developed based on human angiotensin-converting enzyme 2 protein (ACE2) functionalized silvernanotriangle arrays.7 Nanomedicine possess several characteristics that can be used to accurately transporttherapeutic agents to the target cells, and the specific ligand conjugated nanoparticle connects with epitopes ofthe virus, causing the virus to be inactivated and unable to enter the cells. As a result, nanomedicine-basedtechniques that target COVID-19 binding, entry, replication, and budding can be used to neutralize theinfection.8 A number of products based on nanotechnology, like nano-silver is on the market currently due totheir ability to combat viruses. Remdesivir is one of nanomedicine's greatest accomplishments in themanagement of COVID-19 infection. Furthermore, plasmonic nanoparticles (silver, gold and their hybridnanostructures) have anti-infective properties against COVID-19 and have been useful in the development ofdiagnostic assays. For this reason, nanomedicine has shown to be critical in combating the COVID-19 epidemic.5Several nanocarriers have been explored in designing and delivering vaccines such as lipid nanoparticles beable to deliver mRNA into the cytoplasm which directly translate in to the target protein.9 In 2020, UK regulatorsapproved the COVID-19 mRNA encapsulated lipid nanoparticles based vaccine created by Pfizer and BioNTechfor emergency use, followed by authorization of Moderna's vaccine.10 Recently, both of these nanoparticlebased vaccines have been fully approved by the FDA.11 The licensing of the COVID-19 mRNA vaccines wasunquestionably a huge milestone in nanotechnology. Currently ten innovative technologies based on lipidnanoparticles are in clinical pipelines for COVID-19 vaccines.11In conclusion, nanoparticles may play a vital role in COVID-19 pathogenesis at several phases during viral entry.Nano-encapsulated drugs may also be more effective at triggering intracellular pathways that produceirreversible virus damage and limit viral transcription, translation, and reproduction.Going forward, nanoparticle-based vaccines will play mounting role in enhancing vaccination outcomes againstCOVID-19. Scholars may use state-of-the-art nanomedicine as a platform to examine their involvement inmanaging the COVID-19 pandemic with greater efficacy.How to cite this: Awan UA, Saeed RF, Naeem M, Mumtaz S, Qazi AS. State of the Art Nanotechnology to Combat Current COVID-19 Outbreak. Life and Science. 2022; 3(3): 141-142.doi: http://doi.org/10.37185/LnS.1.1.229

Nanoparticles as Physically- and Biochemically-Tuned Drug Formulations for Cancers Therapy.

Simple SummaryConventional antitumor drugs have limitations, including poor water solubility and lack of targeting capability, with consequent non-specific distribution, systemic toxicity, and low therapeutic index. Nanotechnology promises to overcome these drawbacks by exploiting the physical properties of diverse nanocarriers that can be linked to moieties with binding selectivity for cancer cells. The use of nanoparticles as therapeutic formulations allows a targeted delivery and a slow, controlled release of the drug(s), making them tunable modules for applications in precision medicine. In addition, nanoparticles are also being developed as cancer vaccines, offering an opportunity to increase both cellular and humoral immunity, thus providing a new weapon to beat cancer.Malignant tumors originate from a combination of genetic alterations, which induce activation of oncogenes and inactivation of oncosuppressor genes, ultimately resulting in uncontrolled growth and neoplastic transformation. Chemotherapy prevents the abnormal proliferation of cancer cells, but it also affects the entire cellular network in the human body with heavy side effects. For this reason, the ultimate aim of cancer therapy remains to selectively kill cancer cells while sparing their normal counterparts. Nanoparticle formulations have the potential to achieve this aim by providing optimized drug delivery to a pathological site with minimal accumulation in healthy tissues. In this review, we will first describe the characteristics of recently developed nanoparticles and how their physical properties and targeting functionalization are exploited depending on their therapeutic payload, route of delivery, and tumor type. Second, we will analyze how nanoparticles can overcome multidrug resistance based on their ability to combine different therapies and targeting moieties within a single formulation. Finally, we will discuss how the implementation of these strategies has led to the generation of nanoparticle-based cancer vaccines as cutting-edge instruments for cancer immunotherapy.

A review on the recent advances and application of vaccines against fish pathogens in aquaculture.

Globally, aquaculture has faced serious economic problems due to bacterial, viral, and various other infectious diseases of different origins. Even though such diseases are being detected and simultaneously treated with several therapeutic and prophylactic methods, the broad-spectrum activity of vaccines plays a vital role as a preventive measure in aquaculture. However, treatments like use of antibiotics and probiotics seem to be less effective when new mutant strains develop and disease causing pathogens become resistant to commonly used antibiotics. Therefore, vaccines developed by using recent advanced molecular techniques can be considered as an effective way of treating disease causing pathogens in aquatic organisms. The present review emphasizes on the current advances in technology and future outlook with reference to different types of vaccines used in the aquaculture industries. Beginning with traditional killed/inactivated and live attenuated vaccines, this work culminates in the review of modern new generation ones including recombinant, synthetic peptides, mucosal and DNA, subunit, nanoparticle-based and plant-based edible vaccines, reverse vaccinology, and monovalent and polyvalent vaccines.

Multimodality imaging of nanoparticle-based vaccines: Shedding light on immunology.

In recent years, there have been significant innovations in the development of nanoparticle-based vaccines and vaccine delivery systems. For the purposes of both design and evaluation, these nanovaccines are imaged using the wealth of understanding established around medical imaging of nanomaterials. An important insight to the advancement of the field of nanovaccines can be given by an analysis of the design rationale of an imaging platform, as well as the significance of the information provided by imaging. Nanovaccine imaging strategies can be categorized by the imaging modality leveraged, but it is also worth understanding the superiority or convenience of a given modality over others in a given context of a particular nanovaccine. The most important imaging modalities in this endeavor are optical imaging including near-infrared fluorescence imaging (NIRF), emission tomography methods such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) with or without computed tomography (CT) or magnetic resonance (MR), the emerging magnetic particle imaging (MPI), and finally, multimodal applications of imaging which include molecular imaging with magnetic resonance imaging (MRI) and photoacoustic (PA) imaging. One finds that each of these modalities has strengths and weaknesses, but optical and PET imaging tend, in this context, to be currently the most accessible, convenient, and informative modalities. Nevertheless, an important principle is that there is not a one-size-fits-all solution, and that the specific nanovaccine in question must be compatible with a particular imaging modality. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease.

Immune-related therapeutics: an update on antiviral drugs and vaccines to tackle the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic rapidly spread globally. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, is a positive-sense single-stranded RNA virus with a reported fatality rate ranging from 1% to 7%, and people with immune-compromised conditions, children, and older adults are particularly vulnerable. Respiratory failure and cytokine storm-induced multiple organ failure are the major causes of death. This article highlights the innate and adaptive immune mechanisms of host cells activated in response to SARS-CoV-2 infection and possible therapeutic approaches against COVID-19. Some potential drugs proven to be effective for other viral diseases are under clinical trials now for use against COVID-19. Examples include inhibitors of RNA-dependent RNA polymerase (remdesivir, favipiravir, ribavirin), viral protein synthesis (ivermectin, lopinavir/ritonavir), and fusion of the viral membrane with host cells (chloroquine, hydroxychloroquine, nitazoxanide, and umifenovir). This article also presents the intellectual groundwork for the ongoing development of vaccines in preclinical and clinical trials, explaining potential candidates (live attenuated-whole virus vaccines, inactivated vaccines, subunit vaccines, DNA-based vaccines, protein-based vaccines, nanoparticle-based vaccines, virus-like particles and mRNA-based vaccines). Designing and developing an effective vaccine (both prophylactic and therapeutic) would be a long-term solution and the most effective way to eliminate the COVID-19 pandemic.

Poly (lactic-co-glycolic acid) nanoparticle-based vaccines delivery systems as a novel adjuvant for H9N2 antigen enhance immune responses

Poly (lactic-co-glycolic acid) (PLGA) nanoparticle used as vaccine adjuvants have been widely investigated due to their safety, antigen slow-release ability, and good adjuvants activity. In this study, immunopotentiator Alhagi honey polysaccharide encapsulated PLGA nanoparticles (AHPP) and assembled pickering emulsion with AHPP as shell and squalene as core (PPAS) were prepared. Characterization of AHPP and PPAS were investigated. H9N2 absorbed nanoparticles formulations were immunized to chicken, then the magnitude and kinetics of antibody and cellular immune responses were assessed. Our results showed that PPAS had rough strawberry-like surfaces, a large number of antigens could be absorbed on their surfaces through simple mixing. Adjuvant activity of PPAS showed that, PPAS/H9N2 can induce long-lasting and high HI titers, high thymus, spleen, and bursa of fabricius organ index. Moreover, chicken immunized with PPAS/H9N2 showed a mixed high differentiation of CD4+ and CD8a+ T cell, and strong Th1 and Th2-type cytokines mRNA expression. Thus, these findings demonstrated that PPAS could induce a strong and long-term cellular and humoral immune response, and has the potential to serve as an effective vaccine delivery adjuvant system for H9N2 antigen.