Immunogenicity of a Lived-Attenuated Japanese Encephalitis Vaccine in Children after Hematopoietic Stem Cell Transplantation

Japanese encephalitis (JE) virus is one of the most widespread causes of viral encephalitis in Asia and western pacific.  JE causes long-term neurological morbidities and mortality.  National implementation of JE vaccine effectively reduces incidences of JE in Asian countries.  A live-attenuated JE vaccine (SA 14-14-2) has lesser   local reaction and milder systemic side effects compared to inactivated JE vaccine.  Since antibody (Ab) titers to vaccine-preventable diseases decline after hematopoietic stem cell transplantation (HSCT), therefore reimmunization recommendations have been developed for post HSCT survivors.  However, there has been no recommendation for revaccination of JE vaccine in post HSCT recipients.  This study aimed to measure the immunogenic response to the live-attenuated JE vaccine (SA 14-14-2) in post HSCT recipients.  We enrolled patients who underwent allogeneic HSCT at least 2 years, discontinued immunosuppressive agents at least 6 months, and had no evidence of chronic GVHD.  The live-attenuated JE vaccine (SA 14-14-2) was administered to the patients.  JE neutralizing Ab titers were measured before JE vaccination, then at 1^st, 3^rd, 6^th, and 12^th months after vaccination by a plaque reduction neutralizing test.  Patients with Ab titer less than 10 at 3^rd month received a second injection at 6^th month.  Then, the JE titers were tested at 7^th, 9^th, 12^th, and 18^th months.  Side effects of the JE vaccine were recorded by vaccine card supplied to parents or guardians.  A total of 28 patients (M:F = 11:17) with a median age of 13 years (4-21 years) participated in the study.  The median time from HSCT was 4.13 years (2.1-9.8 years).  The underlying diseases were thalassemia (50%) and hematologic malignancies (50%).  Ten patients (36%) had Ab in the preventive range before vaccination (group 1).  Nine of 18 patients (50%) seroconverted at 3^rd month after single JE vaccination (group 2) but only 3 of them had sustained protective Ab levels at 12^th month.  Nine patients remained absence of JE Ab after the 1^st injection (group 3).  Seven of these 9 patients (78%) seroconverted at 3^rd month after 2^nd JE vaccine injection which all of them could sustain the protective Ab levels at 12^th month.  There was no difference of lymphocyte subset (CD4, 8, 16/56, and 19) between these 3 groups.  There was no incidence of systemic reaction reported in this cohort.  In conclusion, post HSCT survivors had low seroconversion rate after single dose of the live-attenuated JE vaccine (SA 14-14-2).  Post HSCT survivors living in or traveling to the JE endemic countries may require at least 2 doses of the JE vaccine to ensure the protective Ab level.