Molecular Biology Of Varicella Zoster Virus Infection

National Institute Of Allergy And Infectious Diseases

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Linked publications & trials

Abstract

Varicella-zoster virus (VZV) establishes latency in human sensory and cranial nerve ganglia during primary infection (varicella), and the virus can reactivate and cause zoster after primary infection. At present, one zoster vaccine is licensed and available for use in the United States. The recombinant zoster vaccine (RZV) consists of recombinant VZV glycoprotein E formulated in AS01B adjuvant. RZV was approved by the Food and Drug Administration for the prevention of herpes zoster in adults aged 50 years and in October 2017 the Advisory Committee on Immunization Practices recommended RZV for use in immunocompetent adults aged 50 years. At present, it is unknown if patients with chronic lymphocytic leukemia (CLL) who have never been treated for their disease or who are receiving Bruton tyrosine kinase inhibitors, which interfere with B cell signaling pathways and may affect antibody responses, can respond well to RZV or other vaccines. In FY 2021 we reported the results of two open-label, single-arm clinical trials in which we measured immune responses against RZV (a vaccine that boosts the immune responses to a virus that persons are already infected with) and against a recombinant hepatitis B vaccine (a vaccine that induces an immune response to a virus that persons have not been infected with) in persons with CLL who had not been treated or who were on a Bruton tyrosine kinase inhibitor. The antibody response to RZV did not differ significantly (p=0.2) between persons with CLL who were on a Bruton tyrosine kinase inhibitor (41.5% of persons responded, defined as >4-fold increase in antibody titer to VZV glycoprotein E) and those with CLL who had not been treated with a Bruton tyrosine kinase inhibitor (59.1% of persons responded). In contrast, only 3.8% of persons with CLL vaccinated with the hepatitis B who had been treated with a Bruton tyrosine kinase inhibitor responded to the vaccine (defined as >10 mIU/ml of antibody to hepatitis B surface antigen) compared to 28% of those with CLL not on the inhibitor (P = .017). Thus, the antibody response to RZV was not affected by treatment with a Bruton tyrosine kinase inhibitor in patients with CLL, while the response to the hepatitis B vaccine was markedly reduced.