Human immunodeficiency virus or HIV is still a disease with no cure. With the incidence rate in the United States, reported by the Centers for Disease Control and Prevention (CDC), at 38,500 diagnoses in 2015, scientists across the globe continue to work diligently to combat HIV.
A team of researchers from Duke Human Vaccine Institute has recently published their work regarding the interplay of natural killer cells (NK cells) and broadly neutralizing antibodies (bnAbs) in the journal Cell. Their efforts hope to provide insight into the development of a vaccine that can be made to protect individuals from future infection.
About half of those infected with HIV experience production of broadly neutralizing antibodies, while the other 50% do not develop bnAbs. Broadly neutralizing antibodies are naturally occurring antibodies that develop too late in ones HIV infection to provide any benefit. This is because HIV has a high mutation rate and the antibodies would no longer recognize the virus.
If administered early enough, the bnAbs show potential in the development and efficacy of a vaccine. To begin, the researchers must understand the molecular mechanisms of host control of bnAb induction. To this end, the team performed a transcriptome analysis of the blood from about 50 HIV-1 bnAb producing patients and around 50 patients with HIV-1 that do not produce bnAbs. Transcriptome analysis is a catalog of the complete set of RNA transcripts that are generated by the genome.
The scientists observed an upregulation of RAB11FIP5 gene that encodes a Rab protein associated with endosomes. NK cells had the highest expression of the gene, which is presumed to be related to dysfunction of the NK cells. NK cells are involved in the regulation of immune cells, specifically CD4+ T follicular helper cells, the cells that interact with B cells to produce antibodies.
This data suggest that NK cells and Rab11 are part of the regulation of HIV-1 bnAb development.
Barton Haynes, M.D., director of the Duke Human Vaccine Institute and senior author of the study says, “This type of immune cell wasn’t previously known to regulate bnAbs. We found a new natural killer cell pathway that appears to be important in regulating the bnAb production.”
Todd Bradley, Ph. D., a lead author of the study, states, “This is a new pathway that we hope to modulate during vaccination to generate a better HIV antibody response.”
The research team identifies future work should focus to identify the specific receptor-ligand interactions involved in triggering of NK cell lysis of CD4+ T cells. They would also like to see if blocking these interactions improves antibody responses during vaccination.