Poster Presentation 13th Australian Peptide Conference 2019

Development of novel self-adjuvanting peptide-based subunit vaccine against herpes simplex virus-2 (#137)

Viet Tram Duong 1 , Sahra Bashiri 1 , Mariusz Skwarczynski 1 , Istvan Toth 2 3 4
  1. University of Queensland, School of Chemistry and Molecular Biosciences, St. Lucia, QLD 4072, Australia
  2. The University of Queensland, School of Pharmacy, Woolloongabba, QLD 4102, Australia
  3. University of Queensland, School of Chemistry and Molecular Biosciences, St. Lucia, QLD 4072, Australia
  4. The University of Queensland, Institute for Molecular Bioscience, St Lucia, QLD 4072, Australia

Herpes simplex virus-2 (HSV-2) infection, the main cause of genital herpes, is prevalent globally. Infection with the virus is lifelong and incurable. Approximately 417 million people worldwide had the infection in 2012. While current antiviral treatment can alleviate the symptoms severity and frequency, they cannot cure the infection completely. This puts more pressure into finding an effective vaccine that can prevent the virus from establishing lifelong latency or recurrent reactivation. Peptide based vaccine employs minimal microbial component and aims to develop long lasting immunity against the pathogen [1]. The HSV-2 envelope glycoproteins bear many important antigens and are responsible for virus adsorption and penetration into host cells. Both humoral and cellular responses play crucial roles in antiviral immunity against HSV-2 [2, 3]. In this study, we have developed four peptide based vaccine candidates that consist of three components: a) a B or  cytotoxic T cell epitope derived from HSV-2 glycoproteins gB, gC and gD; b) a universal CD4+ T-helper epitope; c) a lipid core peptide system [4], in attempt to develop self-adjuvanting vaccine. The peptide vaccines were synthesized using Boc-microwave solid phase peptide synthesis (SPPS). The vaccine candidates were analysed using ESI-MS and analytical RP-HPLC. Purification of the crude peptides were performed on RP-HPLC using C4 column. The  final products have high purity (>98%). Finally, the four compounds were able to self-assemble into nanoparticles with sizes range from 10-1000nm, which are expected to have influence on their biological activities.

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  2. Milligan, G.N., D.I. Bernstein, and N. Bourne, T Lymphocytes Are Required for Protection of the Vaginal Mucosae and Sensory Ganglia of Immune Mice Against Reinfection with Herpes Simplex Virus Type 2.The Journal of Immunology, 1998. 160(12): p. 6093.
  3. Harandi, A.M., et al., Differential roles of B cells and IFN-γ-secreting CD4+ T cells in innate and adaptive immune control of genital herpes simplex virus type 2 infection in mice.2001. 82(4): p. 845-853.
  4. Bartlett, S., M. Skwarczynski, and I. Toth, Lipids as Activators of Innate Immunity in Peptide Vaccine Delivery Current Medicinal Chemistry, 2018. 25: p. 1-14.