Safety, tolerability and immunogenicity of concomitant injections in separate locations of M-M-R II, VARIVAX and TETRAMUNE in healthy children vs. concomitant injections of M-M-R II and TETRAMUNE followed six weeks later by VARIVAX.

OBJECTIVES AND STUDY DESIGN: The primary objectives of this study were to compare immunologic responses, antibody persistence, safety and varicella breakthrough rates when VARIVAX (varicella vaccine) is given at the same time as M-M-R II (measles, mumps, rubella vaccine) and TETRAMUNE (conjugate Haemophilus influenzae type b, diphtheria, tetanus and whole cell pertussis vaccine) at separate injection sites (Group A) vs. VARIVAX given 6 weeks after M-M-R II and TETRAMUNE (Group B). Six hundred nine healthy children, 12 to 23 months of age, were randomized to one of two treatment (immunization) groups (Group A and Group B). Blood for antibody titers was drawn on the day of immunization, 6 weeks after each injection and 1 year later. Local and systemic adverse reactions were recorded. Exposure and cases of varicella were documented through a 1-year follow-up period. RESULTS: Measles, mumps and rubella seroconversion rates and geometric mean titers (GMTs) were similar for both treatment groups. Varicella seroconversion rates were also similar between groups. However, varicella GMTs and percent with a varicella-protective level [> or =5.0 glycoprotein (gp) enzyme-linked immunosorbent assay (ELISA) units] did not meet the prespecified criteria for similarity were lower for Group A (GMT 10.5; 82.8% > or =5.0 gp ELISA units) than for Group B (GMT 14.5; 91.2% > or =5.0 gp ELISA units). The GMTs between groups for other antibodies were similar. At the 1-year follow-up antibody titers were comparable in both groups and breakthrough varicella cases appeared generally similar. There were fewer local adverse events (AEs) at the VARIVAX injection sites (9.8% and 2.9%, Group A and B, respectively) than at the TETRAMUNE sites (27.9% and 24.0%). Systemic AEs were not statistically different when M-M-R II was administered alone (8.6%) or concomitantly with VARIVAX (8.9%). When VARIVAX was given alone AEs were 1.8%. The rate of fever > or =102 degrees F after M-M-R II and TETRAMUNE administered together was 10.7% on Days 0 to 3 and 23.7% on Days 7 to 21. When VARIVAX was administered alone, the rate of fever was 5.4% on Days 0 to 3 (P = 0.018) and 10.8% on Days 7 to 21 (P<0.001). CONCLUSION: Because the varicella titers were comparable and varicella breakthrough rates generally similar at 1 year in both groups, we expect that the concomitant administration of VARIVAX with M-M-R II and TETRAMUNE has clinical effectiveness similar to that with VARIVAX 6 weeks after the administration of these other two vaccines. VARIVAX appears to be less reactogenic than M-M-R II and TETRAMUNE.

Antibody persistence after primary measles-mumps-rubella vaccine and response to a second dose given at four to six vs. eleven to thirteen years.

BACKGROUND: Since 1989 the American Academy of Pediatrics and the ACIP have recommended a second dose of measles-mumps-rubella vaccine (M-M-R-II) at either school entry or age 11 to 13 years. Unfortunately few studies are available to compare responses to vaccine at the two ages. We performed a prospective trial to determine the persistence of antibody to measles, mumps and rubella vaccination in two age groups and the response to a second dose given at either 4 to 6 or 11 to 13 years. METHODS: Thirty-eight children 4 to 6 years old and 57 children 11 to 13 years old were given a second dose of M-M-R-II as they presented for yearly examinations. All had received the first dose at > or = 15 months of age. Measles and rubella antibody were measured by enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody (NT) assay, and mumps antibody was measured by an ELISA method only. An IgM-ELISA antibody assay for measles was used in selected children. Prevaccination and 3- to 4-week post-vaccination sera were obtained. Measles ELISA, measles-neutralizing antibody (NT) and rubella-neutralizing antibody (NT) assays were performed in all children. Seventy-nine of the 95 children had sufficient sera for repeat measles tests, as well as mumps and rubella ELISA determinations. RESULTS: Before the second dose ELISA seropositivity rates for measles and mumps were not significantly different between the two groups. Rubella ELISA seropositivity was 67% in 11- to 13-year-olds, compared with 90% in 4- to 6-year-olds (P < 0.01), suggestive of waning immunity. Rubella NT seropositivity was also lower in 11- to 13-year-olds than in 4- to 6-year-olds (63% vs. 100%, P < 0.01). After revaccination, 100% of the children become seropositive for all 3 antibodies. We performed measles IgM-ELISA testing on all 17 measles-seronegative children, as well as 15 seropositive children and 19 children who were 1 month postvaccination with the first M-M-R-II at 15 months. The purpose was to determine whether the seronegative children were primary or secondary failures. Five of the 17 children with undetectable pre-second dose antibody made IgM measles antibody after revaccination, suggesting that they were primary vaccine failures. CONCLUSIONS: Because all children became seropositive after revaccination, the age of administration can be based on the convenience of vaccine scheduling. However, in view of the apparent decline in rubella antibodies at 11 to 13 years, future studies of rubella vaccination should address the issue of whether earlier boosting leads to greater susceptibility at the time of reproductive age.

Safety and immunogenicity of one vs. two injections of Oka/Merck varicella vaccine in healthy children.

OBJECTIVE: To compare the safety and immunogenicity of a one- vs. two-dose regimen of Oka/Merck varicella vaccine in approximately 2000 healthy children 12 months to 12 years of age. METHODOLOGY: Subjects with a negative history of varicella were randomized to receive either one or two injections of the vaccine given 3 months apart and were followed for clinical reactions and serologic response (glycoprotein-based enzyme-linked immunosorbent assay). RESULTS: Both one- and two-dose vaccine regimens were generally well-tolerated. The incidences of varicelliform rash and fever were less frequent after the second injection. However, a slight increase in the incidence of injection site reactions was noted after the second injection; these were generally mild. Seroconversion rates by glycoprotein-based enzyme-linked immunosorbent assay were 98.2% (1700 of 1731) after one injection and 99.9% (717 of 718) after two injections. A significant (P < 0.001) boost in geometric mean titers was observed in children who received a second injection of vaccine 3 months after the first injection. Of the children who seroconverted at 6 weeks postregimen (one or two doses as assigned), 99.8% (528 of 529) of the one-dose group and 99.8% (473 of 474) of the two-dose group maintained antibody to varicella at 1 year with geometric mean titers of 19.5 and 31.2, respectively. CONCLUSIONS: Administration of a one- or two-dose regimen of the live Oka/Merck varicella vaccine (VARIVAX) is immunogenic and is generally well-tolerated in healthy children 1 to 12 years old. Antibody to varicella persists in > 99% of vaccinees 1 year after vaccination regardless of a one- or two-dose regimen. Long-term follow-up studies of this cohort of children may determine whether a two-dose regimen offers superior protection against chickenpox.

Safety, tolerability, and immunogenicity of two regimens of Oka/Merck varicella vaccine (Varivax) in healthy adolescents and adults. Oka/Merck Varicella Vaccine Study Group.

A multicenter clinical trial was conducted among 757 healthy adolescents and adults, 13-54 years, to compare two regimens of Oka/Merck varicella vaccine with respect to safety, tolerability, and immunogenicity. Participants were randomized to receive two injections of vaccine either four or eight weeks apart and were followed for clinical reactions and serologic response. The two vaccine regimens were equally well tolerated. The seroconversion rates (gpELISA) four weeks after injection 1 and 2 were 72 and 99%, respectively, for those who received vaccine four weeks apart and 78 and 99%, respectively, for those who received vaccine eight weeks apart. The differences in seroconversion rates were not statistically significant. However, delaying the second dose to eight weeks resulted in a higher antibody titer one month after the second injection. Administration of a two-dose regimen of varicella vaccine to susceptible adolescents and adults is well tolerated and highly immunogenic.

Low incidence of adverse experiences after measles or measles-rubella mass revaccination at a college campus.

A postvaccination questionnaire and review of student and employee clinic visits were carried out at Notre Dame University in the spring of 1990 after mass campus revaccination with measles or measles-rubella vaccines in the autumn of 1989, in order to assess the incidence of adverse experiences after revaccination. Rates of adverse experiences (AE), which included chiefly local injection site discomfort and flu-like symptoms, among respondents were 6.6% and 13.4%, male and female students, respectively, and 9.3% and 25%, male and female employees, respectively. Rates of joint-related complaints (4%) were lower than reported after primary vaccination, particularly in young adult women. AEs in general, and joint reaction rates in particular, were generally mild and transient, and only 0.23% resulted in a clinic visit. Revaccination of prior vaccinees appears to be associated with relatively low AE rates.