Texas Biomed scientists awarded NIH grant to develop potential HPV-based HIV vaccine

Scientists at Texas Biomedical Research Institute have begun work on a nearly $3.4 million study funded by the National Institutes of Health over the next four years to create an attenuated, or weakened, virus that is a hybrid of the papilloma virus and the human immunodeficiency virus, with the potential to jumpstart a body's immune response to develop antibodies against both viruses. This study is being done in Rhesus macaques using a form of the rhesus (Rh)PV and monkey HIV or Simian Immunodeficiency virus (SIV).

Dr. Marie-Claire Gauduin, an associate scientist in the Virology and Immunology Department, is leading this effort to develop and test a potential Human papillomavirus (HPV)-based HIV vaccine in monkeys that uses a new strategy integrating a recombinant rhesus papillomavirus (rRhPV) to induce virus-specific immune responses at mucosal genital sites to protect against both HIV and HPV transmission.

"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," Gauduin said. "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."

According to Dr. Gauduin, an ideal vaccine should provide life-long immunity against HIV infection at the site of transmission using viral antigens (or special regions or genes encoding for viral antigens that elicit an immune response) and should focus that immune response at the site of primary replication of HIV, which is the mucosa.

The first step in the study will be to create the hybrid virus that leads to long-term expression of SIV antigens. The second part of the study will investigate the nature of the immune response to the virus followed by investigation of the protective efficacy of the hybrid vaccine when challenged with actual SIV virus.

Nearly 80 percent of HIV infection is spread through mucosa. Gauduin's strategy will use the host's epithelial or skin stem cells as a mucosal delivery system to carry the hybrid virus throughout the mucosal site of infection and keep the immune response on alert.

"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," Gauduin said.

She added, "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."

Currently there is no efficient vaccine developed to prevent transmission of the Human Immunodeficiency Virus (HIV), the agent responsible for Acquired Immunodeficiency Syndrome (AIDS).

According to Gauduin, "The development of an effective vaccine that restricts viral replication at mucosal portals of entry remains our best hope for controlling the HIV pandemic."