Drugs that help slow down and control the infection caused by the human immuodeficiency virus (HIV) are an important therapeutic modality. However, preventing the spread of this deadly disease through the development of prophylactic vaccines is essential for disease elimination. Yet, attempts thus far at creating an effective HIV vaccine have been met with limited success. Now, new research, led by investigators at the University of Copenhagen, paves the way for vaccines that, as opposed to conventional methods, boosts the parts of the immune system attacking the viral genes, which are the least active during the infection. Findings from the new study were published recently in EbioMedicine in an article entitled “Mucosal Vaccination with Heterologous Viral Vectored Vaccine Targeting Subdominant SIV Accessory Antigens Strongly Inhibits Early Viral Replication.”
Traditional vaccines typically cause a strong stimulation of the parts of the immune system, that are most responsive to the specific virus. But the reaction to the vaccine and the infection is often so intense that the immune system loses momentum and consequently is not able to completely eliminate the virus. Researchers have therefore designed a vaccine that boosts the cells of the immune system responsible for the less exposed parts of the virus. As a result, the cells can distribute the workload and retain the defense against the virus attack for a longer period of time. This gives the immune system time to build a more efficient defense, which may then defeat the remaining virus.
“We're presenting an entirely new vaccine solution,” explained senior study investigator Peter Holst, Ph.D., associate professor in the department of immunology and microbiology at the University of Copenhagen. “Our vaccine supports the work of the immune system in developing an effective combating mechanism against the virus, rather than immediately combating the toughest parts of the virus. In combination with other vaccines, this approach can prove to have a highly efficient effect.”
Previous studies by Dr. Holst and his colleagues caused them to develop this new vaccine strategy, which generates so-called strong immune responses against weak immunostimulatory parts of viruses. The investigator's research initially focused on experiments in mice, with the current study looking at the control of simian immunodeficiency virus (SIV) in monkeys.
“We immunized rhesus macaques intramuscularly and rectally using a heterologous adenovirus vectored SIV vaccine regimen encoding normally weakly immunogenic tat, vif, rev and vpr antigens fused to the MHC class II associated invariant chain,” the authors wrote. “Immunizations induced broad T cell responses in all vaccines. Following up to 10 repeated low-dose intrarectal challenges, vaccines suppressed early viral replication (P = 0.01) and prevented the peak viremia in 5/6 animals. Despite consistently undetectable viremia in 2 out of 6 vaccines, all animals showed evidence of infection-induced immune responses indicating that infection had taken place. Vaccines, with and without detectable viremia better preserved their rectal CD4+ T cell population and had reduced immune hyperactivation as measured by naïve T cell depletion, Ki-67 and PD-1 expression on T cells.”
SIV is a chronic infectious disease and a highly realistic representation of HIV. The results from the research team are a major step toward developing a vaccine against HIV and other chronic infections.
“The next phase of our work is to build virus control in all infected animals and later in humans,” Dr. Holst concluded. “We're convinced that it's possible to identify further improvements in our experiments and thus achieve a well-functioning vaccine, initially against HIV, but also against other chronic infections.”