Two studies published in PLOS Pathogens this month shed further light on the effect of neutralizing antibodies in the steep challenge facing researchers to develop a vaccine against AIDS/HIV.
Illustration of CD4
Nabs are immune proteins that can recognize, bind to, and trigger the elimination of a virus.
Image credit: Dr. Alexandra Trkola
The search for an effective vaccine for AIDS/HIV has long been a battle for scientists and researchers around the world. Although HIV incidence has remained stable in the US at 50,000 new infections per year, the life-threatening disease continues to be a major global issue. According to the World Health Organization (WHO), an estimated 2.1 million people became newly infected with HIV globally in 2013, with an effective cure yet to be found.
Neutralizing antibodies are immune proteins that can recognize, bind to, and trigger the elimination of a virus before it can establish a chronic infection. Nabs have previously been researched as a tool against HIV and AIDs. In a study last year, scientists discovered for the first time how to create Nabs in those already infected with HIV-1.
Dr. Julia Overbaugh, from the Fred Hutchinson Cancer Research Center in Seattle, WA, and her team, focused on the role of Nabs in those “superinfected” with HIV, which is defined as those sequentially infected at least twice with HIV by different sexual partners.
Results from 21 women who were tested suggest that Nabs mount a broad and potent response against diverse HIV subtypes. It is hoped that that this particular response can be mediated at least in part by polyclonal antibodies, which can then target different aspects of the virus.
These findings follow on from the team’s previous research into the superinfected. In that study, it was discovered that those infected twice had a more potent antibody response to the virus – which inhibited the virus from replicating – compared with women who have only been infected once.
Dr. Overbaugh hopes further research can be done on those superinfected, stating further research may “provide insight to the development of a diverse Nab response with multiple epitope specificities.”
Direct cell to cell transmission more prone to mutation strains
The second study published in PLOS Pathogens focused on Nabs effect on those infected with HIV/AIDS by cell-to-cell contact. Dr. Alexandra Trkola from the University of Zurich, Switzerland, and her colleagues, developed an assay that can specifically test the potency of Nabs to prevent direct cell-to-cell transmission of HIV.
By establishing an assay system, the free virus infection is restricted, resulting in infections only occurring through cell-to-cell transmissions. Researchers were able to test whether a large selection of Nabs could prevent cell-to-cell transmission of different HIV strains.
Although Nabs showed an overall decrease in activity, losses varied substantially depending on the antibody and virus strain examined. Scientists also discovered certain Nabs still retained activity during cell-to-cell transmission for individual viruses. However, this was generally not linked to a high potency of the free virus, but instead, displayed Nabs inhibiting prior to the binding of the virus to the CD4 receptor on T cells.
Mathematical analysis showed that when the virus was transmitted via cell to cell transmission, it was substantially more prone to give rise to mutation strains that can escape immune control compared to free virus transmissions.
Dr. Trkola said:
“This highlights the importance of controlling virus replication via the cell-cell transmission pathway even if the contribution of this transmission should provide to occur to a less extent than free virus spread in infected individuals.”