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Prime-Boost Rotavirus Vaccine Regimens Are Highly Effective
Published in Lijuan Yuan, Vaccine Efficacy Evaluation, 2022
The protection rates conferred by one of the combined regimens (AttHRV1x/VLP+ISCOM 2xIN) were superior over all the vaccine groups and only slightly lower than that conferred by a prior VirHRV infection (Azevedo et al., 2010; Gonzalez et al., 2004). In evaluating the AttHRV1x/VLP+ISCOM2xIN regimen, Gn pigs were given one oral immunization with Wa AttHRV (5 × 107FFU) and two IN immunizations with 2/6 VLPs at a dose of 250 µg, 100 µg, or 25µg. The dose of ISCOM adjuvant was 1,250 µg per dose. Control pigs received one oral immunization with diluent and two IN immunizations with ISCOM matrix. Two regimens using only IN route were also tested in Gn pigs: 1) one IN dose of Wa AttHRV followed by two IN doses of 250 µg of 2/6VLP and 1,250 µg of ICOM (AttHRV1xIN/VLP+ISCOM2xIN), and 2) three IN doses of AttHRV (AttHRV3xIN). Because lymphocytes sensitized in the nasal lymphoid tissue (NALT) can relocate to distant effector sites through the common mucosal immune system, the respiratory tract was explored as an immunization route to improve rotavirus vaccine efficacy. In addition, AttHRV was found to replicate in nasopharyngeal epithelial cells in Gn pigs (Azevedo et al., 2005) and respiratory symptoms and rotavirus shedding in nasopharyngeal secretions of humans have been reported (Lewis et al., 1979; Nigro and Midulla, 1983; Thi Kha Tu et al., 2020).
Vaccine Adjuvants in Immunotoxicology
Published in Mesut Karahan, Synthetic Peptide Vaccine Models, 2021
Immune-stimulating complexes (ISCOM) are registered liposome adjuvants which contain saponin. The stability and small size of the ISCOM matrices help them remain in the circulation for a long time (Eratalay and Öner 2001). It was shown in several animal models that ISCOM induced both humoral (TH2 induction) and cellular immune response (TH1 induction), and potential cellular responses (such as CT) (Bengtsson, Morein, and Osterhaus 2011; Gül and Dikmen-Yurdakök 2019). A cell-mediated immune response is essential for effective vaccination against intracellular pathogens and chronic infections. ISCOMs can effectively stimulate both CD4+ and CD8+ T cell responses. The technology used leads to an increase in efficiency by decreasing the antigen dose and long-term immune responses (Gül and Dikmen-Yurdakök 2019). Within the scope of ISCOM, saponin-based ISCOMATRIX, which forms spontaneously then saponin, cholesterol, and phospholipid are mixed under controlled conditions, was developed as a versatile helper system which can increase both B cell and T cell responses. It is a system used to decrease the level of the dose administered and to stimulate the immune system (Gül and Dikmen-Yurdakök 2019; Pearse and Drane 2005). It has been reported that the most common adverse event was pain after administration (Pearse and Drane 2005).
Antigen Delivery Systems Used to Induce Immunomodulation
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
M. Zahirul I. Khan, Ian G. Tucker, Joan P. Opdebeeck
Research carried out on experimental models demonstrated that the ISCOM complex is a potent adjuvant when used to deliver various synthetic [106], purified [103], or subunit [104,105] antigens and can induce protective immunity in animals against lethal challenge. The ISCOMs can induce both a humoral response and CMI against the antigen and have the potential for vaccine formulation against viral infections [104]. They are also effective when used to deliver antigens via the oral route [105,107], The uptake of ISCOMs and their transportation to lymphoid tissues are relatively fast [101], and they can cross cell membranes [108], which may be the main factors contributing to the high immune responses obtained in some experiments, but their exact mechanism of action is not clearly understood and requires more investigation [101]. The toxicity issues of the saponin derivative Quil A, which is not approved for human use, are also a matter of concern, although the quantities of Quil A required in ISCOMs are often 5%–10% of the concentration of the incorporated antigen. This amount is sufficient to potentiate a 10-fold increase of the immune response over that obtained with the antigen administered via other systems [102,103,109].
Combined adjuvant-delivery system for new generation vaccine antigens: alliance has its own advantage
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Monika Kaurav, Jitender Madan, M. S. Sudheesh, Ravi Shankar Pandey
ISCOM vaccines were reported to have improved efficacy in several animal studies when saponin-adjuvanted ISCOM vaccines were formulated with parainfluenza-3, rabies and measles viruses. Favorably, ISCOM vaccines protect the adjuvant action of the saponin, while eradicating its haemolytic action risks. They likewise required considerably less amount of antigen and adjuvant to incite immunity in the host than the basic blend of free antigen and saponins [52]. The antigen-adjuvant combination in ISCOMs increased efficacy with improved safety along with reducing antigen production costs have made this vaccine technology highly attractive. Additionally, matrix component alone (ISCOMATRIX adjuvant; the saponin-containing molecule grid detailed without antigen) was likewise exhibited to be a potent adjuvant when physically admixed with free antigen. Several antigens have been tried with ISCOM and ISCOMATRIX adjuvants to develop the robust delivery system. Some are under clinical trials such as HSV (Phase II trial completed) [53], HPV (Phase I trial completed) [54], Influenza (Phase I trial completed NCT00868218), Melanoma (Phase II trial completed NCT00518206) (Table 4). ISCOMATRIX virosomal vaccine provides strong immune responses along with excellent safety profile while tested along with influenza (H5N1).