Novel genetic variation identified at fixed loci in ORF62 of the Oka varicella vaccine and in a case of vaccine-associated herpes zoster.

Quinlivan ML, Jensen NJ, Radford KW, Schmid DS.

Source

Division of Viral Diseases, Measles, Mumps, Rubella, and Herpesvirus Laboratory Branch, Centers for Disease Control and Prevention, Office of Infectious Diseases, National Center for Immunizations and Respiratory Diseases, Atlanta, GA 30333, USA.

Abstract

The live attenuated Oka varicella vaccine (vOka), derived from clade 2 wild type (wt) virus, pOka, is used for routine childhood immunization in several countries including the United States (US), causing dramatic declines in varicella incidence. vOka can cause varicella, establish latency and reactivate to cause herpes zoster (HZ). Three loci in varicella-zoster virus (VZV) open reading frame (ORF) 62 (106262, 107252, 108111) are used to distinguish vOka from wt VZV. A 4(th) position (105705) is also fixed for the vOka allele in nearly all vaccine batches. These 4 positions and two vOka mutations (106710 & 107599) reportedly absent from Varivax were analyzed on Varivax-derived ORF62 TOPO TA clones. The wt allele was detected at positions 105705 and 107252 on 3% and 2% of clones, respectively, but was absent at positions 106262 and 108111. Position 106710 was fixed for the wt allele whereas the vOka allele was present on 18.4% of clones at position 107599. We also evaluated the 4 vOka markers in an isolate obtained from a case of vaccine HZ. The isolate carried the vOka allele at positions 105705, 106262 and 108111. However, at position 107252 the wt allele was present. Thus, all of the ORF62 vOka markers previously regarded as fixed occur as the wt allele in a small percentage of vOka strains. Characterization of all four vOka markers in ORF62 and the Clade 2 subtype marker in ORF38 is now necessary to confirm vOka adverse events.