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Correspondence to Author: Pamila Kranca Bosengarten, 

Research Group Pharmaceutical Biotechnology, Faculty of Applied Natural Sciences, TH Koln - University of Applied Sciences, Germany.

Abstract :
: Developing a preventive vaccination is hampered most by the sequence variety of HIV-1. Trialists are currently testing Mosaic (Mos) antigens, which are made up of artificially scrambled epitopes from different strains of HIV-1 (NCT03964415). The Mosaico vaccine includes vectors that mediate gene transfer and production of the membrane-anchored Env-variant Mos2S.Env in addition to adenovirus vectors encoding variations of the Mos.Gag-Pol and soluble Mos.Env proteins. Therefore, we investigated whether the production of viruslike particles (VLPs) is mediated by the expression of mosaic Gag. The Mos1.Gag- and Mos2.Gag-VLP-formation was easily identified using electron microscopy and Western blot analysis. Co-expression of Mos2S. Env and both mosaic Gag variants resulted in the integration of Env into Gag-formed VLPs. Mos2S.Env-decorated VLPs were shown to display the corresponding neutralization-sensitive target epitopes when a panel of broadly neutralizing antibodies (bNAbs) was used in a VLP-capture test. This provides fresh insights for developing HIV vaccines in the future.

KEYWORDS:
Vaccine development ,Mosaic HIV-1 antigens p55-gag viruslike particles, Broadly neutralizing antibodies, PiggyBac transposon vectors, Suspension cell lines

RESULTS:It is vitally necessary to create a preventive vaccination in order to fight the HIV/AIDS epidemic. A perfect vaccination would stimulate humoral as well as cellular immunity. However, the development of a vaccine is severely hampered by the great genetic heterogeneity of HIV-1 (Gaschen et al., 2002; Ndung’u and Weiss, 2012). To reduce the number of infected cells and, consequently, the viral load, a robust T cell response— especially one that involves CD8+ cytotoxic T lymphocytes (CTLs)—must be triggered (Kiepiela et al., 2007; Janes et al., 2017; Collins et al., 2020). Furthermore, in order to prevent virus cell entrance, a strong vaccination must stimulate the production of broadly neutralizing antibodies (bNAbs) against neutralization-sensitive epitopes found in the viral envelope glycoproteins (Env) (Zolla-Pazner et al., 2014;
So-called mosaic (Mos) HIV antigens, which are composed of artificially shuffled epitope sequences coming from several HIV variations, were created to increase coverage of potential T and B cell epitopes originating from diverse HIV variants (Fischer et al., 2007). When rhesus macaques were vaccinated with an adenovirus vector containing the antigen-encoding genes Mos.Gag, Mos.Pol, and Mos.Env, the results showed that the antigen-specific T cell responses were more extensive and varied than when utilizing consensus or naturally occurring sequences (Barouch et al., 2010). These results served as the foundation for the ongoing Mosaico clinical trial (NCT03964415). In addition to soluble Env proteins acting as booster vaccine subunit components, the The adenovirus vector components Ad26.Mos1.Gag-Pol, Ad26.Mos2.Gag-Pol, Ad26.Mos1.Env, and Ad26.Mos2S.Env are part of the Ad26. Mos4 tetravalent vaccination (Ad26.Mos4) for HIV (Baden et al., 2020). Mos2S.Env, also known as C4D7, is membraneanchored because it possesses a transmembrane region, in contrast to the soluble Mos1.Env. When compared to its fulllength counterpart, the shortened cytoplasmic tail (CT) of Mos2S.Env was demonstrated to enhance surface expression (Langedijk et al., 2019, 2021).

Citation:

Pamila Kranca Bosengarten vaccine components facilitate the production of virus-like particles (VLPs) and the presentation of envelope proteins that reveal broadly neutralizing epitopes. The Journal of Virology 2024.