![]() In this study, we analyzed the influence of VLPs dosing and immunization regimens on the immunogenicity of ZIKV VLPs. ![]() Furthermore, it was shown that the formulation of ZIKV VLPs with various adjuvants (e.g., aluminum hydroxide, squalene-based oil-in-water nanoemulsion) resulted in an increase in neutralizing antibody titers in comparison to nonadjuvanted VLPs when administered in a two-dose regimen via the intramuscular route. The dosage of VLPs used in these studies ranged from 1 to 25 μg of total protein content. The immunogenic potential of ZIKV VLPs has been demonstrated in animal models, and it was shown that compared to inactivated virus, these structures are more immunogenic ( 17, 18). Additionally, capsid protein (C) may be added to the VLPs construct to facilitate production however, this strategy requires coexpression with viral protease to cleave the C protein from prM and E proteins. However, the level of VLPs secretion may be low, and therefore different strategies, such as exchanging the signal sequence of prM protein or the transmembrane domains of E protein to analogous regions of Japanese encephalitis virus (JEV), have been used ( 15, 16). Naturally, two envelope glycoproteins of ZIKV, prM and E, are able to assemble into VLPs and are further secreted to the cell culture medium when expressed together in eukaryotic cells ( 14). Virus-like particles (VLPs) are among the strategies for developing vaccine antigens. Recent studies have shown new ZIKV African strains have emerged in mosquitoes and primates, and these strains are genetically different from pandemic strains by 15% in addition, these strains are more infectious and pathogenic to fetuses ( 10 – 12). Although the overall number of ZIKV infections is now declining e.g., in 2020 in Brazil, there were over 3,500 confirmed cases versus 215,000 in 2016, ZIKV is still actively circulating in Latin America and Asia ( 9). One of the latest reports described new cases of active vector transmission of ZIKV in France ( 7, 8). The geographical range of mosquitoes is still expanding due to climate changes, and there are new reports of active transmission of flaviviruses, e.g., West Nile virus, Usutu virus, dengue virus, and Zika virus ( 6). mosquitoes, although ZIKV can also be transmitted via other routes, i.e., blood transfusion, from mother to child, and via sexual contact. To date, 89 countries have reported Zika virus transmission caused by the spread of Aedes spp. Importantly, the epidemic was followed by a striking increase in the cases of microcephaly in newborns ( 4, 5). In Brazil, the number of ZIKV cases was estimated to be more than 1,300,000 (World Health Organization, 2016). Then, ZIKV quickly spread through the Pacific region to South America in 2015 to 2016, causing an epidemic in those regions. For many years, ZIKV infections were sporadic, then the first large outbreaks occurred in 2007 in the region of Micronesia and in 2013 in French Polynesia, at which time ZIKV was first connected with the neurological disorder Guillain-Barré syndrome ( 2, 3). Zika virus (ZIKV) is a mosquito-borne human pathogen that was discovered in 1947 in West Africa ( 1). ![]() In summary, this is the first report showing the influence of vaccination schedules and adjuvants on the immunogenicity of ZIKV virus-like particles. Sera from mice immunized using an increasing dosing schedule also showed higher neutralization activity against both Zika strains (H/PAN/2016/BEI-259634, a pandemic strain belonging to Asian lineage, and MR766, a reference strain from African lineage). It has been shown that the increasing dosing regimen generates a significantly higher titer of antibodies however, the adjuvant type does not affect this process. These modifications improved the formation of the glycoprotein E dimer. Novel recombinant VLPs (F2A) were designed by introducing the optimized signal sequence of prM protein and by adding a self-cleavage peptide 2A between proteins prM and E. The aim of this study was to produce a potential anti-Zika virus vaccine candidate based on virus-like particles (VLPs) in mammalian cells and to analyze the role of dosing regimen and adjuvant type on the immunogenicity of the obtained antigen. Although different types of vaccine antigens have been investigated, there is still no approved vaccine that prevents ZIKV. Due to the risk of fetuses developing microcephaly, ZIKV is a serious problem for pregnant women. Zika virus (ZIKV) is a reemerging mosquito-borne flavivirus that causes febrile illness and is also linked to Guillain-Barré syndrome as well as to microcephaly in newborns. ![]()
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