A long-term prospective study of varicella vaccine in healthy children.

Abstract

Studies in Japan and the United States have shown that varicella vaccine is both safe and efficacious. In 1984, we undertook a 10-year prospective study using a research lot of Oka/Merck varicella vaccine to assess antibody persistence and breakthrough chickenpox rates. In 1987, we began a similar prospective study with lots made in production facilities that ended after 6 years because many children were given a second dose. The purpose of this study is to report humoral antibody persistence and breakthrough chickenpox rates after 6 to 10 years of prospective follow-up. One hundred forty-three seronegative children received a research lot (950 plaque-forming units/dose) with 97.9% seroconversion by an assay for fluorescent antibody to membrane antigen (FAMA). One hundred thirty-eight children received production lots (1145 to 3265 plaque-forming units/dose) with 93.5% seroconversion. Yearly chickenpox exposure surveys were completed by phone, and children were seen by a study nurse whenever chickenpox was suspected. A subset in each group had serum collected every 2 years and tested for FAMA antibody. In the research group there have been 25 cases of chickenpox in 137 seroconverters in a period of more than 10 years (yearly rate of 1.7%). In the production lot group there have been 22 cases of chickenpox in 129 seroconverters in a 6-year period (yearly rate of 2.8%). In the research group the median titer rose from 1:16 to 1:64 between 1 and 10 years. In the production group, the median titer did not change between 1, 2, and 4 years. Median antibody titers were compared between the research and production groups at 1, 2, and 4 years and did not differ. The rate of development of modified chickenpox has not increased with time since vaccination, and neither has the case severity. Children with FAMA titers </=8 at 6-weeks' postvaccination were four times more likely to develop chickenpox than those with titers >/=64. 1) Modified chickenpox has occurred in approximately 2% to 3% of vaccinees per year, regardless of the vaccine lot given. 2) FAMA titers have risen between 1 and 10 years in research lot recipients and remained the same in production lot recipients. 3) The likelihood of modified chickenpox developing is inversely related to the 6-week postvaccination FAMA titer.