Immunological Characterization of Plant-Based HIV-1 Gag/Dgp41 Virus-Like Particles

Sarah A. Kessans, Mark D. Linhart, Lydia R. Meador, Jacquelyn Kilbourne, Brenda G. Hogue, Petra Fromme, Nobuyuki Matoba, Tsafrir S. Mor

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

It is widely anticipated that a prophylactic vaccine may be needed to control the HIV/AIDS epidemic worldwide. Despite over two decades of research, a vaccine against HIV-1 remains elusive, although a recent clinical trial has shown promising results. Recent studies have focused on highly conserved domains within HIV-1 such as the membrane proximal external region (MPER) of the envelope glycoprotein, gp41. MPER has been shown to play critical roles in mucosal transmission of HIV-1, though this peptide is poorly immunogenic on its own. Here we provide evidence that plant-produced HIV-1 enveloped virus-like particles (VLPs) consisting of Gag and a deconstructed form of gp41 comprising the MPER, transmembrane, and cytoplasmic domains (Dgp41) provides an effective platform to display MPER for use as an HIV vaccine candidate. 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 investigated in BALB/c mice. Serum antibody responses against both the Gag and gp41 antigens were elicited when systemically primed with VLPs. These responses could be recalled following systemic boosting with VLPs. In addition, mucosal priming with VLPs allowed for a boosting response against Gag and gp41 when boosted with either candidate. Importantly, the VLPs also induced Gag-specific CD4 and CD8 T-cell responses. This report on the immunogenicity of plant-based Gag/Dgp41 VLPs may represent an important milestone on the road towards a broadly efficacious and inexpensive subunit vaccine against HIV-1.

Original languageEnglish
Pages (from-to)e0151842
JournalPLoS One
Volume11
Issue number3
DOIs
Publication statusPublished - Jan 1 2016

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virus-like particles
Human immunodeficiency virus 1
Viruses
Virion
HIV-1
Membranes
vaccines
Vaccines
Virus-Like Particle Vaccines
virus-like particle vaccines
gag Gene Products
AIDS Vaccines
Subunit Vaccines
Membrane Fusion
cholera toxin
subunit vaccines
Cholera Toxin
T-cells
Antibody Formation
roads

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Kessans, S. A., Linhart, M. D., Meador, L. R., Kilbourne, J., Hogue, B. G., Fromme, P., ... Mor, T. S. (2016). Immunological Characterization of Plant-Based HIV-1 Gag/Dgp41 Virus-Like Particles. PLoS One, 11(3), e0151842. https://doi.org/10.1371/journal.pone.0151842

Immunological Characterization of Plant-Based HIV-1 Gag/Dgp41 Virus-Like Particles. / Kessans, Sarah A.; Linhart, Mark D.; Meador, Lydia R.; Kilbourne, Jacquelyn; Hogue, Brenda G.; Fromme, Petra; Matoba, Nobuyuki; Mor, Tsafrir S.

In: PLoS One, Vol. 11, No. 3, 01.01.2016, p. e0151842.

Research output: Contribution to journalArticle

Kessans, SA, Linhart, MD, Meador, LR, Kilbourne, J, Hogue, BG, Fromme, P, Matoba, N & Mor, TS 2016, 'Immunological Characterization of Plant-Based HIV-1 Gag/Dgp41 Virus-Like Particles', PLoS One, vol. 11, no. 3, pp. e0151842. https://doi.org/10.1371/journal.pone.0151842
Kessans, Sarah A. ; Linhart, Mark D. ; Meador, Lydia R. ; Kilbourne, Jacquelyn ; Hogue, Brenda G. ; Fromme, Petra ; Matoba, Nobuyuki ; Mor, Tsafrir S. / Immunological Characterization of Plant-Based HIV-1 Gag/Dgp41 Virus-Like Particles. In: PLoS One. 2016 ; Vol. 11, No. 3. pp. e0151842.
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