A team of scientists at Texas Biomedical Research Institute received a grant from the National Institutes of Health worth almost 3.4 million dollars to develop a Papillomavirus-based HIV vaccine that offers protection simultaneously against HIV and HPV transmission. The awarded work is entitled “A trans-complementing Papillomavirus for AIDS Vaccine,” and could be translated into an efficient vaccine against Human Immunodeficiency Virus (HIV).
The study led by Dr. Marie-Claire Gauduin, an associate scientist in the Virology and Immunology Department, is being developed in Rhesus macaques with rhesus (Rh)PV and monkey HIV or Simian Immunodeficiency virus (SIV). The devised strategy consists of triggering virus-specific immune responses at the site of infection of both HPV and HIV, i.e. in the genital mucosa, with a recombinant rhesus papillomavirus (rRhPV). The immune response triggered against the viral antigens should elicit a life-long immunity against HIV infection at its primary site of transmission, the genitalia.
Dr. Marie-Claire Gauduin noted, “This strategy would represent the first attempt to immunize animals with a trans-complementing live attenuated RhPV-SIV vector virus replicating at the major port of entry of SIV/HIV and RhPV/HPV, which is the mucosa. The study will also explore the feasibility of such vaccine delivery platforms to stimulate the mucosal (adaptive and/or innate) immune responses to restrict viral entry.”
The study involves two stages — in the first stage of the research, the team is developing a hybrid virus to express the SIV antigens for long periods. In the second stage, the team will evaluate the hybrid virus induced immune response and determine the protective response of the hybrid vaccine when challenged with a wild-type SIV virus. Since HIV infection for the most part spreads through mucosa, the team will use epithelial cells or skin stem cells as the vehicle to deliver hybrid virus and activate the immune system.
Dr. Marie-Claire Gauduin added, “What’s exciting about this is that if we can place the vector vaccine in just the right layer of the mucosa, it will promote antibody production and anti-SIV central memory CD8+ T cell expansion at the site of infection for a prolonged period of time, initiating the immune system, preventing HIV infection and/or propagation and generate immediate protection. In addition, we will generate anti-SIV cell expansion within the vaginal and rectal mucosa. Remember, skin grows out and sheds creating new layers of skin. As it does this, we hope to create an antibody response memory in the mucosal layer so that as skin regenerates, future layers retain this immune response. In other words, this novel HIV vaccine strategy will use the host epithelial stem cells as mucosal ‘delivery systems’ to ‘carry’ viral antigen and keep the immune response in alert at site of viral infection.”
The study findings will be applied to develop a vaccine to prevent transmission of the Human Immunodeficiency Virus (HIV), the causing agent of Acquired Immunodeficiency Syndrome (AIDS).
“The development of an effective vaccine that restricts viral replication at mucosal portals of entry remains our best hope for controlling the HIV pandemic,” Gaudin concluded.