Search Content

Matching Items (2)

Filtering by

All Subjects: VLP
Creators: Hogue, Brenda

Biological and immunological characterization of plant-produced HIV-1 Gag/dgp41 virus-like particles

Description

Anti-retroviral drugs and AIDS prevention programs have helped to decrease the rate of new HIV-1 infections in some communities, however, a prophylactic vaccine is still needed to control the epidemic world-wide. Despite over two decades of research, a vaccine against HIV-1 remains elusive, although recent clinical trials have shown promising results. Recent successes have focused on highly conserved, mucosally-targeted antigens within HIV-1 such as the membrane proximal external region (MPER) of the envelope protein, gp41. MPER has been shown to play critical roles in the viral mucosal transmission, though this peptide is not immunogenic on its own. Gag is a structural protein configuring the enveloped virus particles, and has been suggested to constitute a target of the cellular immunity potentially controlling the viral load. It was hypothesized that HIV-1 enveloped virus-like particles (VLPs) consisting of Gag and a deconstructed form of gp41 comprising the MPER, transmembrane, and cytoplasmic domains (dgp41) could be expressed in plants. Plant-optimized HIV-1 genes were constructed and expressed in Nicotiana benthamiana by stable transformation, or transiently using a tobacco mosaic virus-based expression system or a combination of both. Results of biophysical, biochemical and electron microscopy characterization demonstrated that plant cells could support not only the formation of HIV-1 Gag VLPs, but also the accumulation of VLPs that incorporated dgp41. These particles were purified and utilized in mice immunization experiments. Prime-boost strategies combining systemic and mucosal priming with systemic boosting using two different vaccine candidates (VLPs and CTB-MPR - a fusion of MPER and the B-subunit of cholera toxin) were administered to BALB/c mice. Serum antibody responses against both the Gag and gp41 antigens could be elicited in mice systemically primed with VLPs and these responses could be recalled following systemic boosting with VLPs. In addition, mucosal priming with VLPs allowed for a robust boosting response against Gag and gp41 when boosted with either candidate. Functional assays of these antibodies are in progress to test the antibodies' effectiveness in neutralizing and preventing mucosal transmission of HIV-1. This immunogenicity of plant-based Gag/dgp41 VLPs represents an important milestone on the road towards a broadly-efficacious and inexpensive subunit vaccine against HIV-1.

ContributorsKessans, Sarah (Author) / Mor, Tsafrir S (Thesis advisor) / Matoba, Nobuyuki (Committee member) / Mason, Hugh (Committee member) / Hogue, Brenda (Committee member) / Fromme, Petra (Committee member) / Arizona State University (Publisher)

Created2011

The Potential of Virus-Like Particles (VLPs) as an Effective Vaccine Candidate for the COVID-19 Vaccine: Review

Description

Virus-like particles (VLPs) are optimum candidates for creating vaccines, as they are highly flexible, adaptable, safe, and similar to the structural proteins of the target cells. The COVID 19 pandemic has increased the need to create effective and safe vaccines that can be mass produced to stop the spread of COVID-19. Till now, various types of vaccine platforms have been utilized to create COVID-19 vaccines, each with unique characteristics and techniques. It is essential to use robust vaccine platforms that can deliver optimum results in a short period of time, with minimal risks. The structural proteins found in SARS-CoV-2, such as Spike (S) protein have been widely targeted to induce antibody response, also called a humoral response, which is a part of acquired immunity. The other structural proteins such as M (membrane) and E (envelope) can also be used as targets for antibodies. The S2 and glycoprotein (S full) can be used to induce an efficient IgG response. Therefore, the incorporation of structural proteins into VLPs can prove to be useful. Furthermore, double mosaic VLPs employs double epitopes, which can effectively cover the distances between the S proteins, thus optimizing the B cell activation process. This review describes the various developments that have taken place in the field of VLPs and more specifically, with regards to developing VLP vaccines against the SARS-CoV-2 virus.

ContributorsSharma, Anjali (Author) / Hogue, Brenda (Thesis director) / Li, Yize (Committee member) / Barrett, The Honors College (Contributor) / College of Health Solutions (Contributor)

Created2022-05