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An investigational tetravalent combined measles, mumps, rubella, and varicella vaccine and measles-mumps-rubella and varicella vaccines at separate injection sites given at the same visit were evaluated with respect to safety and cell-mediated and humoral immune responses at 6 weeks and 1 year after vaccination. Varicella seroconversion rates and lymphocyte proliferation responses were 100% for both vaccine groups at 6 weeks and 1 year. However, the antibody titer to varicella was lower in the combined vaccine group at 6 weeks, but there was no statistical difference in cell-mediated immune responses. One-year geometric mean titers were not statistically different. Seroconversion rates for measles, mumps, and rubella were 100% for both vaccine at 6 weeks and 1 year. Long-term follow-up of these immune responses is planned.

Administration of two doses of hepatitis A (HA) vaccine to childrenor = 2 years of age has been shown to be protective. The present study assessed whether HA vaccine can be administered as early as 6 months of age and whether it can be administered concomitantly with a hexavalent (HV) vaccine at this age.In an open label, randomized, parallel group study, the liquid HV vaccine (HEXAVAC) (diphtheria, tetanus, 2-component acellular pertussis, inactivated poliomyelitis vaccine, Haemophilus influenzae type b conjugated to tetanus protein and hepatitis B) was administered at 2, 4, 6, and 12 months of age to all children. HA vaccine (VAQTA) was given at 7 and 13 months in the separate administration group (Group 1) and at 6 and 12 months in the concomitant administration group (Group 2). Serum samples were obtained at 2, 7, 12, and 14 months in Group 1 and at 2, 7, 12, and 13 months in Group 2. The primary immunogenicity outcomes were the seroconversion rates for HA 1 month after the second dose of HA vaccine in initially seronegative subjects, and the seroconversion rates for each HV antigen 1 month after the third dose of the HV vaccine (both at 7 months of age).HA seropositivity rates 1 month after the second dose were 100% in both groups, regardless of initial serostatus. The responses to each HV antigen 1 month after the third dose were similar in both groups. The vaccines were generally well tolerated in both groups regardless of vaccine(s) administered.A schedule of two doses of HA vaccine, 6 months apart beginning at 6 months of age is highly immunogenic and well tolerated when administered alone or concomitantly with HV vaccine at 6 and 12 months of age.

Pain at the injection site is one of the most commonly-reported local reactions associated with administration of a vaccine, but it has not been quantified by a validated instrument for pain measurement. We conducted a randomised, double-blind clinical trial to evaluate the measurement characteristics of two commonly-used pain questionnaires, the McGill Present Pain Intensity (PPI) and the Brief Pain Inventory (BPI) Current Pain Question, in the assessment of intramuscular injection-site pain associated with vaccine administration. The PPI measures pain on a scale of 0 (no pain) to 5 (excruciating pain) and the BPI measures pain on a scale of 0 (no pain) to 10 (pain as bad as you can imagine).Two hundred healthy adults were randomised to one of the five regimens: tetanus and diphtheria toxoids adsorbed (Td), aluminum hydroxide adjuvant (alum), physiological saline, or one of the two licensed hepatitis A vaccines, VAQTA, or HAVRIX. Pain assessment was made at eight time-points over a 2-day period after injection.The differences in the time-averaged pain (+/- standard deviation) on the PPI were statistically significant between Td (0.58+/-0.59) and either saline (0.14+/-0.23) (p0.005) or alum (0.22+/-0.35) (p0.01). Reported time-averaged pain were significantly lower for VAQTA than HAVRIX (p = 0.028). Similar differences were observed for the BPI.Both instruments have sufficient discriminative validity to distinguish between different levels of injection-site pain in adults.

To determine the safety and immunogenicity of concurrent administration of measles-mumps-rubella-varicella vaccine (MMRV) and PedvaxHIB (Haemophilus influenzae type b conjugate vaccine) vs. M-M-R II and PedvaxHIB followed by an optional dose of VARIVAX 6 weeks later.Healthy children, 12 to 18 months of age, were randomly assigned to two groups to receive (1) MMRV and PedvaxHIB given concurrently or (2) M-M-R II and PedvaxHIB followed by an optional dose of VARIVAX 6 weeks later.The study group included 294 healthy children, ages 12 to 18 months, with a negative history of measles, mumps, rubella and varicella.The seroconversion rate and magnitude of antibody responses when MMRV was given concurrently with PedvaxHIB compared with the antibody responses when VARIVAX was given 6 weeks after M-M-R II and PedvaxHIB.Healthy children, 12 to 18 months of age, who received MMRV and PedvaxHIB concurrently showed immune responses similar to those in the control group who received M-M-RII vaccine with PedvaxHIB followed by VARIVAX 6 weeks later. Antibody titers for varicella were significantly lower when MMRV was administered than when varicella vaccine was given separately (0.712-fold difference, P = 0.028). No vaccine-related serious adverse reactions were reported, and no clinically significant differences were seen in the safety profiles of the two treatment groups.There were no statistically significant differences in the seroconversion rates between the two treatment groups for any of the antigens tested at 6 weeks and 1 year. Significantly lower geometric mean titers for varicella were noted in the group who received MMRV compared to VARIVAX given alone. Six-week seroconversion rates, persistence of immune responses at 1 year and the frequency of local and systemic reactions were comparable when MMRV was administered with PedvaxHIB compared with M-M-R II and PedvaxHIB followed by VARIVAX 6 weeks later.

Recent papers examining the expected persistence of anti-hepatitis A virus antibody following vaccination with inactivated hepatitis A vaccine have estimated that geometric mean antibody levels will remain above cut-off levels for 10-30 years. However, the methodology used in these papers did not take into account any estimates of variability between subjects. In this paper data from the persistence of antibody after the administration of another vaccine, VAQTA (hepatitis A vaccine, inactivated; MSD), were used to develop further models of antibody decay. Using individual subject estimates instead of group means allowed the estimation of time to negativity for various percentiles of the population (including the median), and the construction of confidence intervals on estimates of time to negativity. Data from studies of subjects who seroreverted to negativity, and subsequently received a booster dose, were also considered to show that subjects who lose detectable antibody are likely to remain protected from hepatitis A disease by persistent immune memory and rapid anamnestic response soon after exposure to hepatitis A virus. The estimates of duration of protection suggest that VAQTA will provide protection for many years, first through presence of antibody and further through an anamnestic response based on persistent immune memory.

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.

A total of 3303 healthy children and adolescents, aged 12 months to 17 years, were vaccinated with one of five production lots of a live attenuated varicella vaccine (VARIVAX) containing 1000 to 1625 plaque-forming units per dose. The vaccine was generally well tolerated. Ninety-six percent (2381/2475) of vaccinees responded to vaccination by producing antibody as measured by a glycoprotein-based enzyme-linked immunosorbent assay; 99% (569/576) of those tested maintained antibody at 1 year following vaccination. The incidence of varicella following household exposure in vaccinees was approximately 12%; household contact historically results in 87% infection. Nearly all of the vaccinees who had varicella after vaccination had a clinically modified disease.

A clinical trial among 137 healthy children, ages 1 to 12 years, was conducted with four different doses (4,350, 870, 435, and 43 plaque-forming units [pfu]) of live Oka/Merck varicella vaccine to evaluate clinical reactions and selected laboratory parameters and to determine the minimum effective dose and induction time of antibody. The vaccine was well tolerated with no significant difference in the rate of reported symptoms by dose. The frequency of varicellalike rash was 3% (4/137); all rashes were mild. Serum aminotransferase values were essentially unchanged after vaccination. Minor variations found in platelet counts after vaccination were not associated with any bleeding, bruising, or clotting. Among initially seronegative children who received doses of 435 pfu or greater, 94% assayed at two weeks and 100% assayed at four or six weeks seroconverted. The geometric mean titers were similar for all four doses at six weeks. IgG and IgA responses were demonstrated with no relation to the vaccine dose.

Oka strain varicella vaccine generally has been well tolerated by children with acute lymphocytic leukaemia (ALL) in remission and has induced protection against disease caused by wild-type varicella virus. At the end of 1985, four extensive vaccine-associated rashes were reported among children on maintenance chemotherapy. Steroid therapy in the week before vaccination or in the week following vaccination was significantly associated with rash in a retrospective analysis (odds ratio = 3.84, p = 0.0006). These findings were confirmed prospectively (OR = 2.38, p less than 0.05, one-sided) in a second smaller group of children with ALL on maintenance therapy who received varicella vaccination after the end of the data collection for the initial study but before the relationship between rash and steroids was discovered. As a result of these studies, investigators have been asked to withhold steroids for 1 week before vaccination and to delay resumption of steroid therapy for at least 2 weeks after vaccination. These results should serve as a caution that vaccination of these children should be undertaken only with full knowledge of their therapeutic regimen and a thorough clinical understanding of the competing risks of varicella, vaccination and modification of the child's chemotherapy.

To determine the need for immunization of health workers with antibody to hepatitis B surface antigen (anti-HBs) as their only serologic marker of previous hepatitis B exposure, we studied the level, persistence, and immunologic specificity of isolated anti-HBs in 46 persons identified during screening for hepatitis B vaccine. We rescreened these persons 1 year later, administered a single dose of hepatitis B vaccine, and determined the anti-HBs level at 1, 2, and 8 weeks after vaccination. Isolated anti-HBs levels were low and antibody did not persist; 22 subjects tested had lost detectable anti-HBs within 19 months even though immunologic specificity was shown in vitro in 34. Anamnestic responses suggesting previous exposure and immunity were seen in only 10 subjects; 5 of these subjects had moderate-level, persistent anti-HBs. Although some persons with naturally acquired, isolated anti-HBs may be protected from hepatitis B, the immunologic specificity and protective value of anti-HBs, especially when levels are low, remain questionable.