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Clinical Trials of COVID-19 Therapeutics and Vaccines
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Candan Hizel Perry, Havva Ö. Kılgöz, Şükrü Tüzmen
In the context of viral vector vaccine strategies, the gene of interest is incorporated into the genome of a recombinant or modified viral vector to express specific antigens as a delivery platform [8]. The gene coding for an antigen can be controlled by a specific promoter integrated into the vector and elicit both T cell and high-titer antibody responses as it mimics the natural infection even without the need of an adjuvant [8, 25]. Because of their distinct features, different types of viral vectors have been used for antigen-specific immunization strategies. Nevertheless, some viral vectors can induce low immunogenicity through pre-existing immunity [17, 25, 27]. Viral vaccine vectors can be further classified as two main groups, depending on their ability of replication in host cells: replicating viral vectors (RVV) and non-replicating viral vectors (NRVV) [19]. NRVVs are still capable of infecting/transducing host cells, promoting the expression of desired antigens [8]. At the time of writing there are 20 viral vector candidate vaccines for SARS-CoV-2 in clinical phase assessment, including 6 RVV and 14 NRVV vaccine candidates [21].
Multiple Evanescent White Dot Syndrome Following Adenovirus Vector-Based COVID-19 Vaccine (Covishield)
Published in Ocular Immunology and Inflammation, 2023
Abhilasha Baharani, Raja Rami Reddy
The proposed mechanisms for vaccine-induced uveitis are: (1) direct infection of ocular tissues with live vaccine, (2) molecular mimicry between vaccine constituents and ocular tissues resulting in cell and antibody mediated hypersensitivity reactions and (3) autoimmune reactions induced by vaccine adjuvants or additives (Schoenfeld syndrome). These are usually aluminium salts used in subunit/inactivated vaccines.16 Molecular mimicry seems to be a likely mechanism in the present case. The viral vector vaccine interacts with cell ribosomes resulting in production of translated proteins on the cell membranes which induces activation of Th cells and antibodies.3 Uveitis may result from a hypersensitivity reaction between translated proteins and ocular tissues. The “danger signals” triggered by the inflammatory mediators of the innate immune system are essential to elicit an immune response. Therefore, though inflammatory responses are the basis of vaccine induced adverse reactions, they are also vital for the development of adaptive immunity. Inflammation mediated adverse events following vaccination might potentially indicate a stronger immune response.17
The race for a COVID-19 vaccine: where are we up to?
Published in Expert Review of Vaccines, 2022
Md Kamal Hossain, Majid Hassanzadeganroudsari, Jack Feehan, Vasso Apostolopoulos
Viral vectors are a biological technology that has been used in science and medicine since the 1970s. Very recently, this platform has been used to control the Ebola outbreaks. In this technology, the genetic material (DNA) of a viral vector vaccine is carried within a harmless adenovirus, adeno-associated virus, retrovirus, and lentivirus [64]. Vaccine development using this platform has been widely explored. The genome of one virus is used to deliver the antigen of another virus in this platform. This platform has been validated for large-scale commercial production. However, it has some limitations, such as a significant variation in purification methods, leading to inaccurate purity and activity of the vaccines. This platform has been explored for a number of vaccines such as Ebola, Marburg virus, influenza, Chikungunya, Zika, Lassa mammarena virus, Human/Simian immunodeficiency virus, cancers, and many more [65–67]. Currently, approximately 59 candidates using this platform are under investigation for a COVID-19 vaccine. However, viral vectors may trigger the risk factors, including genotoxic events, e.g. inflammation, random insertion disrupting normal genes, activation of proto-oncogenes, and insertional mutagenesis [68].
Passive and active antibody studies in primates to inform HIV vaccines
Published in Expert Review of Vaccines, 2018
Ann J. Hessell, Delphine C. Malherbe, Nancy L. Haigwood
The partial efficacy of the RV144 clinical trial [28] also increased interest in the development of viral vector vaccine delivery systems. In particular, the double-stranded DNA poxvirus vectors (MVA, NYVAC, and ALVAC), which have an extensive safety record, have been used as priming agents to elicit T-cell responses. In a recent head-to-head comparison between NYVAC and ALVAC, the vaccine regimen with NYVAC was shown to induce stronger cellular and humoral immune responses [151]. Recently, a DNA–MVA–protein vaccine was shown to elicit mucosal immunity in lymph nodes (LNs) [152]. Another type of viral vectors actively pursued is adenovirus (Ad) since it is able to target mucosal sites, an important feature for HIV vaccines. Ads can infect dividing and nondividing cells and generate humoral and cellular immune responses while also accommodating large transgenes. However, the main drawback is the anti-vector immunity in particular to highly prevalent serotypes such as human Ad5, which was included in the failed STEP trial. This issue was partially resolved by using serotypes with lower prevalence such as human Ad4, Ad26, Ad35, and A48. Ad26, Ad35, and Ad48 are non-replication competent whereas Ad4 is replication competent which has the potential to better mimic natural HIV infection and to act as adjuvant. Ad26 used in an Ad prime/protein boost approach recently showed 50% protection against SIV IR challenge [153]. Another solution was to develop Ad vectors based on Ads from other species (chimpanzees and rhesus macaques), but these vectors do not replicate in humans and may not confer immunity that is as potent. There was evidence for significantly better viral control in a recent study that combined either human Ad4 or simian Ad7 expressing Gag and Env with recombinant Env protein [154].