HIV is a virus that can attack the human immune system. It takes the important CD4+ T lymphocytes in the human immune system as the main target of attack, and destroys these cells in large quantities, causing the human body to lose its immune function.
Structure of wild type HIV-1. (Cervera L, et al., 2019)
Genome of HIV-1
HIV is an enveloped virus that belongs to lentiviruses (a subgroup of the retrovirus family) whose genome consists of two similar single-stranded RNA molecules and several viral proteins packaged within a capsid. Two types of HIV have been identified, HIV-1 and HIV-2, based on genetic characteristics and viral antigens. HIV-1 and its subtypes are the main types of viruses responsible for the global AIDS pandemic. The HIV-1 genome includes 9 functional genes: 3 structural genes (gag, pol, env), 2 regulatory genes (tat, rev) and 4 accessory genes (vif, vpu, vpr, nef), some of which are in different have overlapping sequences on the frame.
Schematic representation of HIV-1 genome with its 9 coding genes. (Cervera L, et al., 2019)
Challenges of HIV Vaccine
The failure of HIV vaccine immunization is primarily due to the extraordinary genetic diversity of HIV-1, and more specifically the env glycoprotein, which is a target of neutralizing antibodies, with a high level of variability, approximately 1-10 mutations per genome replication cycle. HIV-1 has developed a unique set of mechanisms to evade neutralizing antibodies, enabling both hosts to generate HIV mutants that escape neutralizing antibodies (nAbs). Therefore, an ideal HIV-1 vaccine candidate should elicit a balanced immune response, can bind high titers of nAbs, additional antibody-dependent cell cytotoxicity (ADCC) and phagocytic activity.
Plant-produced HIV VLP Vaccine
The advantages shown by VLP as an HIV-1 vaccine are as follows.
Can trigger a strong immune response.
Non-infectious due to lack of genetic material.
Surface exposure of native env trimeric proteins is necessary for the induction of neutralizing antibody production.
Granular properties promote VLP uptake by antigen presenting cells (APCs), resulting in strong cellular responses against gag and env.
The optimal production process for HIV-1 VLPs should be cost-effective, high-yield, scalable, and provide VLPs with the correct structure and immunogenicity. Plants offer an interesting alternative for VLP production, and their hosts include N. benthamiana, alfalfa, A. thaliana, rice, potato, and soybean, among others. As a platform for VLP production, plants do not need expensive equipment and production measures, and are easy to be produced on a large scale. In addition, the risk of plant infection by pathogens of human origin is minimal, and the vaccine produced is particularly suitable for oral administration.
Plant-made HIV vaccines. (Tremouillaux-Guiller J, et al., 2020)