A multivalent polyomavirus vaccine elicits durable neutralizing antibody responses in macaques

Area of Science:

• Virology
• Immunology
• Transplant Medicine

Background:

• Kidney transplants are vital, but engrafted organs face risks from polyomaviruses like BKPyV and JCPyV.
• Polyomavirus-associated nephropathy (PyVAN) is a significant cause of graft loss, often detected via BKPyV viremia.
• Current management involves reducing immunosuppression, increasing rejection risk; high neutralizing antibodies may offer protection.

Purpose of the Study:

• To evaluate the immunogenicity and safety of a multivalent virus-like particle (VLP) vaccine against BKPyV and JCPyV.
• To determine if VLP vaccination can induce protective levels of neutralizing antibodies against these viruses.

Main Methods:

• Production of VLPs for BKPyV genotypes I, II, IV, and JCPyV genotype 2 in insect cells.
• Immunization of rhesus macaques with single-genotype or multivalent VLP vaccines.
• Measurement of antibody titers and neutralizing antibody responses over time.
• Monitoring for vaccine-related adverse events.

Main Results:

• All vaccinated macaques developed robust neutralizing antibody titers above the proposed protective threshold.
• A booster inoculation significantly increased antibody titers, which remained elevated for nearly two years.
• No adverse events were observed, indicating a favorable safety profile for the VLP vaccine.
• Multivalent VLP immunogens performed comparably to single-genotype vaccines.

Conclusions:

• BK/JC VLP vaccines are immunogenic and safe in a preclinical non-human primate model.
• These findings support the development of a multivalent VLP vaccine for kidney transplant recipients to prevent PyVAN.
• A clinical trial is warranted to assess the efficacy of this VLP vaccine in preventing PyVAN in transplant patients.