Comparison of One-versus Two-dose Varicella Vaccines

This study was undertaken to compare the immunogenicity and reactogenicity of two vaccines based on the attenuated Oka-strain of Varicella zoster virus (VZV), in adolescents and young adults. One hundred and eighty-six subjects, aged 13 to 29 years, were randomized to one of two groups to receive a oneor a two-dose VZV vaccine. Preand post-vaccination blood samples were assayed for VZV-specific IgG. Solicited local and general symptoms, as well as unsolicited symptoms, were recorded post-vaccination. Seroconversion rates were 94.9% in the one-dose, and 100% in the two-dose, regimen. The two-dose vaccine elicited significantly higher geometric mean antibody titer, 392.5 vs 86.8 pfu. Transient local injection site pain was the most frequently-reported symptom per dose in both groups (one dose: 48.9%; two-dose: 32.8%). The two-dose vaccine regimen afforded the advantage of higher antibody titers and potential increased protection from disease, without significantly increased reactogenicity. Academy of Pediatrics and the Advisory Committee for Immunization Practices (ACIP) have included varicella immunization into the routine schedule. Their recommendations for the VZV vaccine in the USA include universal use of one dose in children aged 12 months to 12 years and two doses 4-8 weeks apart in susceptible adolescent and adult populations (ACIP, 1999; Committee on Infectious Diseases, 2000), a recommendation supported by the Centers for Disease Control (Centers for Disease Control and Prevention, 1996; White, 1997). Other countries in which routine childhood vaccination has been adopted include Canada, Japan, Korea, and Uruguay. Although Finland is the only European country to date that has adopted a universal childhood vaccination policy, the European Working Group on Varicella Vaccination (EuroVar) has proposed an immunization strategy consistent with that of the ACIP (Rentier, 2000). Mathematical modeling, using a range of values for vaccine efficacy at different rates of vaccine coverage, suggest that routine immunization of pre-school children would greatly reduce the number of primary varicella cases (Halloran et al, 1994a,b; Halloran, 1996). The World Health Organization (2001) advises that routine childhood immunization be considered in countries where this disease is a relatively important public health and socioeconomic problem, where the vaccine is affordable, and where high SOUTHEAST ASIAN J TROP MED PUBLIC HEALTH 698 Vol 35 No. 3 September 2004 85%-90% and sustained vaccine coverage can be achieved. In addition, immunization of adolescents and adults without a history of varicella, and in particular those at increased risk of contracting and spreading infection, is recommended. This study was undertaken to assess the immunogenicity and reactogenicity of a oneand a two-dose schedule of two VZV vaccines (both Okastrain) in susceptible adolescents and young adults. MATERIALS AND METHODS One hundred and eighty-six teenagers and young adults (aged 13 to 29) were enrolled into this open prospective study, conducted at Khon Kaen University, Khon Kaen, Thailand. The study was approved by the institutional ethics review board and was conducted according to the Declaration of Helsinki and Good Clinical Practice guidelines effective at study initiation. Written informed consent in the local language was obtained from the subjects or parents or guardians (dependent upon the age of the subject) prior to entry into the trial. Subjects were excluded if they had received previous vaccination against varicella, had a clear history of clinical varicella/zoster infection, prevaccination serum-positive for varicella antibody, as determined by enzyme linked immunosorbent assay (ELISA), or had known exposure to varicella/zoster within four weeks prior to study vaccination. Other exclusion criteria were acute or chronic disease, chronic drug therapy, immunosuppressive therapy or receipt of immunoglobulins or blood products within three months prior to vaccination, history of allergic disease, confirmed or suspected immunodeficient conditions, chronic alcohol consumption and/or intravenous drug abuse. Pregnant or lactating females, or females of childbearing potential who were not using contraceptive precautions, were not included in the study. Eligible subjects were randomized into one of two groups to receive either Biken Institute (Biken) vaccine which consists of a single dose, according to its prescribing information, or GlaxoSmithKline Biologicals’ (GSK) vaccine which is recommended as a two-dose schedule in subjects ≥13 years of age (with a six-week interval between the two vaccinations). Biken vaccine (distributed by Aventis Pasteur) has a potency of not less than 10 plaque-forming units (pfu) per dose. VarilrixTM produced by GSK contains ≥10 pfu/dose. Both vaccines were reconstituted before use with the diluent provided by the manufacturer and administered subcutaneously into the non-dominant upper arm. Preand post-vaccination blood samples were assayed for varicella zoster (VZV)-specific IgG, using a commercial indirect immunofluorescence (IIF) technique (VirgoTM by Pharmacia). Samples that showed no fluorescence or barely visible fluorescence at the 1:4 starting dilution were considered seronegative. Seroconversion was defined as the appearance of antibodies in the serum of subjects who were initially seronegative (ie IIF titer ≥1:4 in the serum of a subject who was previously seronegative). Local injection site symptoms (pain, redness, and swelling) were solicited on the day of vaccination and for three subsequent days. All vaccinees were followed for 42 days after vaccination for the occurrence of general symptoms (fever defined as axillary temperature ≥37.5°C and rash/exanthem). Subjects were asked to record temperature daily and any other findings on diary cards, and to contact the investigator immediately if they developed any rash at the injection site or generalized rash, if they were exposed to anyone with varicella/zoster, or if they felt any symptom they thought was serious or required medical attention. Any post-vaccination rash was evaluated and its relationship to vaccination determined by the investigator. The sample size was determined based upon the expected ability to accrue seronegative adults. Fisher’s exact test was used to compare seroconversion rates and the incidence of symptoms. Wilcoxon’s test was used to compare geometric mean titers (GMT) of anti-VZV, which were calculated using log transformation of positive titers and taking the antilog of the mean of the transformed titers. Alpha was 0.05.