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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Plant Sci. | doi: 10.3389/fpls.2019.01378

Production and immunogenicity of soluble plant-produced HIV-1 subtype C envelope gp140 immunogens

Emmanuel Margolin1, 2,  Rosamund Chapman1,  Ann Meyers2*, Michiel van Diepen1, Phindile Ximba1, 2, Tandile Hermanus3, 4, Carol Crowther3, 4, Brandon Weber5,  Lynn Morris3, 4,  Anna-Lise Williamson1, 6 and  Edward Rybicki2, 6
  • 1Division of Medical Virology, Faculty of Health Sciences, University of Cape Town, South Africa
  • 2Biopharming Research Unit, Department of Molecular and Cell Biology, University of Cape Town, South Africa
  • 3National Institute of Communicable Diseases (NICD), South Africa
  • 4Faculty of Health Sciences, University of the Witwatersrand, South Africa
  • 5Division of Medical Biochemistry & Structural Biology, Faculty of Health Sciences, University of Cape Town, South Africa
  • 6Institute of Infectious Diseases and Molecular Medicine (IDM), Faculty of Health Sciences, University of Cape Town, South Africa

The development of effective vaccines is urgently needed to curb the spread of human immunodeficiency virus type 1 (HIV-1). A major focal point of current HIV vaccine research is the production of soluble envelope (Env) glycoproteins which reproduce the structure of the native gp160 trimer. These antigens are produced in mammalian cells, which requires a sophisticated infrastructure for manufacture that is mostly absent in developing countries. The production of recombinant proteins in plants is an attractive alternative for the potentially cheap and scalable production of vaccine antigens, especially for developing countries. In this study we developed a transient expression system in Nicotiana benthamiana for the production of soluble HIV Env gp140 antigens based on two rationally selected virus isolates (CAP256 SU and Du151). The scalability of the platform was demonstrated and both affinity and size exclusion chromatography (SEC) were explored for recovery of the recombinant antigens. Rabbits immunised with lectin affinity-purified antigens developed high titres of binding antibodies, including against the V1V2 loop region, and neutralising antibodies against Tier 1 viruses. The removal of aggregated Env species by gel filtration resulted in the elicitation of superior binding and neutralising antibodies. Furthermore, a heterologous prime-boost regimen employing a recombinant modified vaccinia Ankara (rMVA) vaccine, followed by boosts with the SEC-purified protein, significantly improved the immunogenicity. To our knowledge this is the first study to assess the immunogenicity of a near-full length plant-derived Env vaccine immunogen.

Keywords: HIV, glycoprotein, trimer, Plants, Immunogenicity, modified vaccinia Ankara

Received: 29 May 2019; Accepted: 07 Oct 2019.

Copyright: © 2019 Margolin, Chapman, Meyers, van Diepen, Ximba, Hermanus, Crowther, Weber, Morris, Williamson and Rybicki. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Ann Meyers, Biopharming Research Unit, Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa, ann.meyers@uct.ac.za