New Generation Vaccines for COVID-19 Based on Peptide, Viral Vector, Artificial Antigen Presenting Cell, DNA or mRNA

At present, effective vaccines have been developed as the most successful approaches for preventing widespread infectious disease. The global efforts are focusing with the aim of eliminating and overcoming the Coronavirus Disease 2019 (COVID-19) and are developing vaccines from the date it was announced as a pandemic disease. In this study, PubMed, Embase, Cochrane Library, Clinicaltrial.gov, WHO reports, Science Direct, Scopus, Google Scholar, and Springer databases were searched for finding the relevant studies about the COVID-19 vaccines. This article provides an overview of multiple vaccines that have been manufactured from December 2020 up to April 2021 and also offers a perspective on their efficacy, safety, advantages, and limitations. Currently, there are several categories of COVID-19 vaccines based on Protein Subunit (PS), Inactivated Virus (IV), Virus Like Particle (VLP), Live Attenuated Virus (LAV), Viral Vector (replicating) (VVr) and Viral Vector (non-replicating) (VVnr) in progress or finalized as indicated by the WHO reporting of April 1, 2020.

Tailored Nanoparticles as Vaccine Components

Nanoparticles are components of many vaccines, helping to make them more stable and immunogenic. They protect antigens—or the genetic material encoding them—from degradation, target them to particular tissues or cells, promote their uptake into antigen-presenting cells, and activate the immune response (in the form of adjuvants). Nanoparticles come in many different kinds, some with uniform composition and some with elaborate core-and-shell structures, including lipid membranes. The antigen is usually retained inside, and the surface can be functionalized by targeting or activating proteins and carbohydrates. This minireview provides a general introductory overview to vaccination and a survey of nanoparticles, their types, production, characteristics, and individual applications in vaccines, and finally, a brief look into the world of artificial antigen-presenting cells.

Design of antigen synthesis and identification of its artificial antigen for zearalenone

Background: study aimed to modify the ZEN molecule and conjugate the carrier protein to prepare a complete antigen. To lay the foundation for the preparation of ZEN monoclonal antibodies. Methods: The carbonyl group at the 7 position of ZEN molecule was modified by deuteration reaction. The immunogen and antigen were synthesized by EDC method and mixed acid anhydride method, and the complete antigen was identified by UV, IR and electrophoresis. Antisera were obtained after immunization of animals, and an antiserum was designed by ELISA. Results: The immunogens were identified by UV, IR and electrophoresis, ZEN-BSA was successfully synthesized. The ratio of ZEN-BAS to ZEN was calculated to be 1 : 13. When the antibody serum was detected, the titer of the antibody reached 1:(6.4×103). Conclusion: This study demonstrated that the OAE method is preferable in preparing the ZEN. These findings lay the material and technical foundation for the preparation of anti-ZEN monoclonal antibody

Design of Hapten Synthesis and Antibody Characterization of G-group Aflatoxins

Food and feed contamination with Aflatoxins pose a serious threat to human health and animal husbandry development and has caused widespread concern, among them, G-group Aflatoxins as the main pollutant has attracted more and more attention. In order to establish a rapid, sensitive, specific and efficient immunoassay method for G-group aflatoxins, this study aimed to designed to synthesize 3 immunogens and coating antigens and identified by UV and SDS-PAGE. Then used to immunize Balb/c mice with prepared of three immunogen the titers were determined by indirect ELISA and the sensitivity was determined by competitive indirect ELISA (icELISA), the specificity was assessed by the cross-reaction test (CR). The results of UV and SDS-PAGE showed that the three immunogens and the corresponding coated antigens were successfully synthesized and the best one was SA method among three synthesis methods of G-group AF artificial antigen and its conjugation ratio of AFG1 to BSA was about 5.64∶1. The immune efficacy of SA method was the best, its AFG1 pAb had high titers of 1∶(6.4×103) by indirect ELISA, a good sensitivity with the 50 % inhibition concentration(IC50) of 13.6 μg/kg－1 to AFG1 by blocking ELISA and a high CR to AFG2 of 82.19 %, it showed high specificity for other aflatoxins. The experimental results not only obtained the ideal G group aflatoxin antibody, but also established a substance and technology foundation for G group aflatoxin immunization methods, and can be referenced in the similar tests.

Nanoparticles Engineered as Artificial Antigen-Presenting Cells Induce Human CD4+ and CD8+ Tregs That Are Functional in Humanized Mice

Artificial antigen-presenting cells (aAPCs) are synthetic versions of naturally occurring antigen-presenting cells (APCs) that, similar to natural APCs, promote efficient T effector cell responses in vitro. This report describes a method to produce acellular tolerogenic aAPCs made of biodegradable poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) and encapsulating IL-2 and TGF-β for a paracrine release to T cells. We document that these aAPCs can induce both human CD4+ and CD8+ T cells to become FoxP3+ T regulatory cells (Tregs). The aAPC NP-expanded human Tregs are functional in vitro and can modulate systemic autoimmunity in vivo in humanized NSG mice. These findings establish a proof-of-concept to use PLGA NPs as aAPCs for the induction of human Tregs in vitro and in vivo, highlighting the immunotherapeutic potential of this targeted approach to repair IL-2 and/or TGF-β defects documented in certain autoimmune diseases such as systemic lupus erythematosus.

A phase 1 study of RTX-321, an engineered red blood cell as an artificial antigen-presenting cell expressing HLA-A*02 with the HPV-16 E7 peptide and 4-1BB ligand with membrane-bound IL-12 for the treatment of HPV 16-positive cancers.

TPS2664 Background: High-risk strains of HPV (HPV 16/18) have been associated with the development of multiple cancers, and the associated viral antigens are validated targets from immunotherapy approaches. We engineered red blood cells into allogeneic, off-the-shelf, artificial antigen-presenting cells (aAPCs) that express a human papillomavirus (HPV) 16 E7 peptide bound to human leukocyte antigen (HLA)-A*02:01, the costimulatory molecule 4-1BB ligand (L), and the cytokine interleukin (IL)-12 on the cell surface. This aAPC, RTX-321, activated HPV specific T-cells and promoted effector function in vitro. In animal models using a murine surrogate system, this aAPC approach resulted in robust antigen-specific T-cell expansion, NK cell expansion, tumor control, memory formation and antigen spreading, which led to a broad and robust antitumor immune response . The presence of 4-1BBL and IL-12 induced minimal toxicities in these models due to restriction of the biodistribution of the aAPC to the vasculature and spleen. RTX-321 is a potential in vivo cellular immunotherapy for treating HPV 16-positive cancers including cervical, head and neck and anal cancers. Methods: The RTX-321-01 study is a phase 1 multi-center, dose-escalation study of RTX-321 administered intravenously every 3 weeks in HLA-A*02:01-positive patients with relapsed or refractory HPV 16-positive cancers of the cervix or anal canal, or squamous cell cancers of the head and neck (HNSCC). Patients with cervical cancer or HNSCC will undergo testing for the presence of the HPV 16 virus or provide confirmation from archival tumor tissue prior to enrollment. Patients with anal cancer will not be required to have prospective determination of HPV 16-positive status prior to enrollment given the high incidence in this indication (approximately 80-85 percent of anal cancers). Approximately 18 patients will be enrolled across dose level cohorts to identify the recommended phase 2 dose (RP2D) of RTX-321, followed by RP2D expansion cohorts in specific indications. The starting dose is 1 billion (1x109) cells administered intravenously every 3 weeks (Q3W) and the dose will escalate by half-log increments, following a Bayesian logarithmic regression model (BLRM) with overdose control. Translational studies will investigate the activation and expansion of HPV16 E7 antigen-specific responses as well as broad innate and adaptive responses in multiple peripheral blood samples over the first 3 cycles of therapy as well as in optional paired tumor biopsies. At this time, the study is open and enrolling patients in the first dose escalation cohort (NCT04672980). Clinical trial information: NCT04672980.