BKV and JCV vaccine development

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

Two distinct polyomaviruses, called BKV and JCV, chronically infect the human urinary tract. Most healthy adults are stably infected with both viruses and occasionally shed infectious virions in the urine. Although BKV and JCV aren't known to cause overt symptoms in healthy individuals, each of the two viruses can cause severe pathology in immunocompromised individuals. Most notably, BKV causes acute kidney damage in up to 10% of kidney transplant recipients. In AIDS patients and patients taking certain immunosuppressive drugs, JCV can cause a fatal brain disease called progressive multifocal leukoencephalopathy (PML). Our group has recently demonstrated a causal relationship between BKV/JCV infection and the development of bladder cancer among transplant patients. It is conceivable these viruses cause a fraction of bladder and other cancers in the general population. Our goal for this project is to develop preventive vaccines that might protect at-risk patients against BKV associated nephropathy (BKVN) or PML. The vaccines would draw on the same approach that led to the current highly successful vaccines against human papillomaviruses - specifically, the BKV or JCV vaccine would consist of recombinant virus-like particles (VLPs) composed solely of the viral major capsid protein VP1. The VLP vaccine would be aimed at eliciting antibody responses capable of neutralizing the infectivity of BKV or JCV virions. Recent clinical trial results using BKV-neutralizing antibodies to treat BKV nephropathy confirm that this approach is likely to be effective. During FY25, we have continued to support an industry partner that is developing a traditional intramuscular vaccine against BKV and JCV. As part of this support work, we explored the possibility of producing VLPs using brewer's yeast. This work was successful and it led to the surprising discovery that simply feeding VLP yeast to mice can induce BKV and JCV neutralizing antibody responses at titers that correlate with protection against nephropathy in human subjects. We are currently preparing manuscripts covering the exciting discovery and hope to have them submitted by the end of FY25.