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The content of IgA, IgM, IgG and the level of specific antibodies in the blood serum of patients with bronchopulmonary diseases after a course of immunotherapy with polycomponent vaccine B[symbol: see text]-4 was studied. A rise in the concentration of IgM due to the synthesis of specific antibodies to Proteus vulgaris, Escherichia coli and Klebsiella pneumoniae was found to occur. The examination of sick children revealed that a high proportion of them (54%) showed a pronounced decrease in the level of IgA. The use of the preparation made it possible to enhance the level of IgA.

In regulating vaccines, the US Food and Drug Administration (FDA) is governed by the Code of Federal Regulations. These regulations serve as the framework for product characterization, as well as preclinical and clinical testing strategies. Novel vaccine approaches such as combination vaccines, vectored vaccines, new adjuvants, and novel delivery systems pose unique regulatory challenges for the FDA. If US licensure is sought, communication with the FDA throughout the clinical development of a product is essential to identify and implement the appropriate strategies for demonstrating the safety and effectiveness of a new product.

To improve the immunogenicity of melanoma self-antigens, we used a novel strategy of nonviral genetic vaccination coupled with muscle electroporation. Electroporation-enhanced immunization with plasmids encoding either human gp100 or mouse TRP-2 antigens induced only partial rejection of B16 melanoma challenge. However, immunization with a combination of these two antigens caused tumor rejection in 100% of the immunized mice. Splenocytes from combination-immunized animals killed syngeneic targets loaded with peptides derived from both gp100 and TRP-2. Immune cell depletion experiments identified CD8+ T lymphocytes as the primary effectors of antitumor immunity. Most importantly, polyimmunization led to the generation of a therapeutic immune response that significantly improved the mean survival time of mice bearing established lung metastases. These results validated the usefulness of electroporation-enhanced, nonviral genetic immunization for the active immunotherapy of cancer and indicated that using a combination of different tumor antigens may be a decisive strategy for a successful therapeutic vaccination.

An open randomized trial involving 301 subjects was conducted in order to compare the reactogenicity and immunogenicity of a new measles, mumps and rubella (MMR) vaccine, SB MMR, with those of a commercial MMR vaccine, Merck MMR, when given as a second dose to children at 11-12 y of age. All subjects had previously received Merck MMR in the first year of life. In initially seronegative subjects, all subjects receiving the Merck MMR vaccine had seroconverted with respect to measles (10/10 subjects), mumps (38/38) and rubella (4/4). Of the subjects receiving SB MMR, 6/7 seroconverted with respect to measles, 29/31 with respect to mumps and 3/3 with respect to rubella. No difference was seen in seroconversion rates or geometric mean values (GMVs) between groups. In initially seropositive subjects, a higher anti-mumps immune response rate was observed in the SB MMR group (59.3%) compared with the Merck MMR group (24.1%). Higher post-vaccination anti-mumps and anti-rubella GMVs were observed in the group receiving SB MMR (p < 0.007), whereas higher anti-measles GMVs were observed in the Merck MMR group (p = 0.0013). There was a lower (p = 0.013) incidence of pain at the injection site in subjects receiving SB MMR (20.1%) compared with Merck MMR (33.3%). Incidences of systemic reactions were similar between groups.

Acute otitis media (AOM) is the most frequent bacterial infection in childhood. Because of the high morbidity, the costs of AOM and growing concern about increasing resistance of pneumococci, the most common bacterial cause of AOM, prevention of AOM is important. Vaccination with the recently developed pneumococcal conjugate vaccines leads to a reduction in the number of AOM cases caused by the serotypes present in the vaccine, but the reduction in overall AOM incidence is below 10%. In particular the children with recurrent episodes of AOM may benefit more from these pneumococcal conjugate vaccines.

The correlates of long-term protection from measles infection are poorly understood. We followed the development of measles-specific antibody and lymphoproliferative (LP) responses in 60 children for 6 months after MMR vaccination. Prevaccine plaque reduction neutralization antibody (PRN Ab) values were low (mean+/-SEM 9.9+/-1. 1). Ninety-three percent (56/60) had excellent PRN values at 6 months (PRN 1816+/-207). Prevaccine LP activity was also low (stimulation index (SI)=1.4+/-0.1) but increased rapidly (SI 10. 7+/-4.5 at 2-3 weeks; p<0.05). However, only 61% (37/60) of the children had both significant cellular and antibody responses (SI>/=3 and PRN>/=120: Ab(hi)CMI(hi)). One child had a strong LP response (SI=6.7) despite little antibody production (PRN=19 at 6 months: Ab(lo)CMI(hi)). We also conducted a cross-sectional study in a separate group of 87 children 5-13 years after MMR vaccination. PRN values >/=120 were present in most children at 5-8 (n=28) and 9-13 years (n=59) after vaccination (PRN 550+/-120 and 360+/-60, respectively) but a significant minority had either undetected or 'subprotective' values (29 and 34%, respectively). LP responses (SI>/=3) were detectable in 19/28 (66%) and 36/59 (56%) of the children 5-8 and 9-13 years after vaccination (SI 11.4+/-2.4 and 7. 75+/-1.9, respectively). Almost two thirds (18/28) of the children in the cross-sectional study with low or absent antibody titers (PRN 41+/-6) had strong LP responses to measles antigens (SI 6.8+/-1.3). These data suggest that LP responses may be better sustained than antibody titers in some children. The susceptibility of Ab(lo)CMI(hi) children to infection and the value of the early LP response for predicting the durability of immunity remain to be determined.

The immunogenicity and protective efficacy afforded by intramuscular inoculation of plasmid DNA encoding equine herpesvirus 1 (EHV-1) glycoprotein D (gD) followed by EHV-1 gD expressed by a recombinant baculovirus was assessed in a murine model of EHV-1 respiratory infection. Compared with mice inoculated with DNA or protein only, mice inoculated with the combination of gD DNA and protein had enhanced ELISA and neutralizing antibody titres to EHV-1 and had accelerated clearance of virus from lungs following challenge infection. The enhanced protective effects of this consecutive immunization were also evident in mice which had a previous infection with EHV-1 and had pre-existing antibodies. The T-helper 1 (Th1) type of immune response induced by EHV-1 gD DNA was maintained after the protein boost, despite the gD protein alone appearing to direct a Th2 response.

The humoral immune response after primary and re-vaccination confirmed the high immunogenicity of the combined vaccines used: "MMR-Vax(R)", "Pluserix(R)" and "Triviraten(R)". The investigation of paired serum samples of prevaccinal seronegative infants (n90-100% for all three components with the exception of the mumps component of "Triviraten(R)" (38%). However, by additional methods (plaque neutralisation test, immunofluorescence test) mumps antibodies could be detected in 93.4% of infants having received vaccine "Triviraten(R)". The mean values of antibody activities against the three components did not differ significantly after vaccination with "MMR-Vax(R)" and "Pluserix(R)". However, after vaccination with "Triviraten(R)" the mean antibody values were significantly lower (P<0.01) against the measles strain "Edmonston-Zagreb" and especially lower (2-20 times) against the mumps virus strain "Rubini". Revaccination of pre-vaccinal seropositive schoolchildren and adolescents (n=676) with "MMR-Vax(R)" and "Pluserix(R)" produced no different results. The rate of vaccinees responding with a booster reaction reached 68.4% for measles and mumps, but only 8.6% for rubella. A booster reaction could be observed in 100% of those vaccinees who had antibodies at a low level, also in the case of naturally acquired immunity. The low-level range for antibodies against measles was defined as 0.15<0. 40 IU/ml, mumps 1:230

The results of prolonged observations on children with frequent acute respiratory diseases (ARD), subject to immunoprophylaxis with the use of polycomponent vaccine (VP-4), prepared from the antigens of opportunistic microorganisms, are presented. The vaccine was introduced to 30 children in 3 intranasal administrations and 6-8 oral administrations. The morbidity rate of the children was registered and their clinical status was evaluated for a year after the introduction of vaccine VP-4. As revealed in these observations, the frequency of ARD cases among the immunized children decreased 3 times or more in comparison with that among the same children, registered during a year prior to the introduction of the vaccine. In addition to a decrease in the frequency of ARD cases, a decrease in their duration and in the number of antibiotic administrations, as well as in the necessity of hospitalization, were also registered.

Previous studies have suggested that infant vaccinations may reduce the risk of subsequent childhood leukaemia. Vaccination histories were compared in 439 children (ages 0-14) diagnosed with acute lymphoblastic leukaemia (ALL) in nine Midwestern and Mid-Atlantic states (USA) between 1 January 1989 and 30 June 1993 and 439 controls selected by random-digit dialing and individually matched to cases on age, race and telephone exchange. Among matched pairs, similar proportions of cases and controls had received at least one dose of oral poliovirus (98%), diphtheria-tetanus-pertussis (97%), and measles-mumps-rubella (90%) vaccines. Only 47% of cases and 53% of controls had received any Haemophilus influenzae type b (Hib) vaccine (relative risk (RR) = 0.73; 95% confidence interval (CI) 0.50-1.06). Although similar proportions of cases (12%) and controls (11%) received the polysaccharide Hib vaccine (RR = 1.13; 95% CI 0.64-1.98), more controls (41%) than cases (35%) received the conjugate Hib vaccine (RR = 0.57; 95% CI 0.36-0.89). Although we found no relationship between most infant vaccinations and subsequent risk of childhood ALL, our findings suggest that infants receiving the conjugate Hib vaccine may be at reduced risk of subsequent childhood acute lymphoblastic leukemia. Further studies are needed to confirm this association and, if confirmed, to elucidate the underlying mechanism.

Cases of invasive Haemophilus influenzae type b disease in Alaskan children quickly dropped 10-fold after widespread vaccination with a conjugate vaccine (PRP-OMP) began in 1991. However, reemergence of invasive disease in 1996-97 soon followed a change to a combination diphtheria-tetanus toxoid-pertussis/H. influenzae type b vaccine which incorporates a different conjugate vaccine (HbOC). Previously unrecognized persistence of H. influenzae type b carriage in rural Alaska, coupled with characteristics of the immune response to HbOC, are the likely explanations for disease reemergence. The current vaccine recommendation--PRP-OMP for the first dose, followed by HbOC to complete the vaccination series--appears to protect Alaskan infants even in the face of continuing carriage and transmission. Successful control of invasive H. influenzae type b disease in Alaskan children will require not only appropriate immunization, but also continuing surveillance for both disease and carriage, identification of factors associated with carriage, and investigation into the feasibility of using vaccination plus antimicrobial drugs to eliminate this pathogen.

The live attenuated vaccine strains Vibrio cholerae CVD 103-HgR and Salmonella typhi Ty21a can be combined into an oral bivalent vaccine without compromising the immunogenicity of the individual vaccine strains. Seroconversion rates of 87 to 94% for Inaba vibriocidal antibodies and 72 to 91% for anti-S. typhi lipopolysaccharide antibodies (IgG or IgA) were reported in healthy European volunteers receiving a bivalent CVD 103-HgR/Ty21a vaccine-based schedule (bivalent vaccine on day 1 and monovalent Ty21a vaccine on days 3 and 5). The immunogenicity of bivalent CVD 103-HgR/Ty21a vaccine is not adversely affected by concomitant administration of mefloquine, yellow fever vaccine or oral polio vaccine. Chloroquine may reduce the immunogenicity of the CVD 103-HgR component and proguanil may reduce the immunogenicity of the Ty21a component. Bivalent CVD 103-HgR/Ty21a vaccine does not adversely affect the immunogenicity of the yellow fever YF 17D vaccine. The type, incidence and severity of adverse events seen in individuals receiving bivalent CVD 103-HgR/Ty21a vaccine-based schedules are similar to those that occur with the monovalent vaccines.

To evaluate the priming effect, immunogenicity and safety of an Haemophilus influenzae type b (Hib) tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-acellular (two component) pertussis (DTaP) combination vaccine, a randomized, comparative study was conducted in two centers, one in Belgium and one in Turkey. A total of 410 healthy infants, 160 in Belgium and 250 in Turkey, randomly received DTaP and PRP-T vaccines in one of three fashions. One group (N = 138) received DTaP and PRP-T vaccines reconstituted immediately prior to injection at 3, 4 and 5 months of age, and are referred to as the combined, short schedule group (Co-S). A second group (N = 135) received DTaP + PRP-T simultaneously but injected at different sites according to the same schedule, and are referred to as the associated, short schedule group (As-S). The third group (N = 137) also received DTaP + PRP-T at separate sites, but at 2, 4 and 6 months, and are referred to as the associated, long schedule group (As-L). The As-L group allowed for serological bridging with a Senegalese two-component pertussis vaccine efficacy trial, using the same batch of DTaP vaccine. Children of both short-schedule groups (Co-S and As-S) received, at the age of 12-14 months, a booster dose of DTaP vaccine associated with unconjugated PRP vaccine. Mixing of the vaccines did not affect the immune response to the antigens included in the DTaP vaccine. The immune response to Hib capsular polysaccharide, however, was significantly lower after combined administration (Co-S group) than after associated (As-S group) administration (P < 0.0001), with a similar trend among both countries (GMTs, 1.78 microg/ml and 6.19 microg/ml in Belgium, and 5.02 microg/ml and 11.67 microg/ml in Turkey). Booster vaccination with the unconjugated PRP induced a vigorous and similar anamnestic response in both groups. Belgian infants showed a significantly lower immune response to all antigens than Turkish infants (P < or = 0.001 for all antigens), with a similar trend among each study group. In all groups, the incidence of adverse events was lower than that usually reported after DTwP(whole-cell) vaccine. Higher rates of systemic reactions were observed in the Belgian population, possibly due to differences in reporting practice. Our results indicate (1) that the combination vaccine, DTaP//PRP-T, represents an important improvement over the existing uncombined vaccines; (2) that immunogenicity studies should include at least one booster injection to evaluate priming effects by combined vaccines; and (3) that it is feasible and valuable to co-randomize combination vaccine studies in sufficiently different geographical areas and child populations.

In 1997 83,558 cases of mumps were reported and attack rate of 216.3/100,000 was two times higher than in the previous year. Four percent of cases were admitted to hospitals (3,327) and the percentage of hospitalised children ranged from 0.3% in Chełm voivodeship to 12.9% in Konin voivodeship. Mostly affected were children in the age group 5 to 9 years old in which attack rates ranged from 1,602 to 2,293 per 100,000. Patients in this age group constituted 59% of total number of mumps. MMR vaccine is still not included into the national programme of immunization; instead monovalent measles vaccine is used. MMR vaccine is used on voluntary basis.

Hepatitis B (HB) vaccine has been included in the national immunization programmes of more than 90 countries world-wide. Its combination with DTP (diphtheria-tetanus-pertussis) and other childhood vaccines will lower administration costs, simplify vaccine administration and improve the logistics of vaccine delivery. It is believed that the combined vaccines will increase acceptance and vaccine coverage. The immunogenicity and reactogenicity of the various components should not differ when given separately or together. The combined vaccines DTP + HB, DT + HB, HA + HB, HB + Hib have already been developed and used in several countries and DTP + HB + IPV and DTP + HB + IPV + Hib combined vaccines are currently under development. Further studies are necessary to devise appropriate schedules adjusted to the epidemiological situations of each geographic region.

The serological response to MMR vaccine was evaluated in 109 9-month-old infants having no history of measles vaccination, and in 98 15-month-old children who had received monocomponent measles immunisation at 9 months. The combined vaccine contained Schwarz, Urabe Am9, and Wistar RA 27/3 live attenuated virus strains. Preimmunisation antibody levels were extremely low for the 9-month-old children, indicating that maternally-transmitted antibodies do not persist at this age. In the case of mumps, preimmunisation antibody levels were significantly higher in the 15-month-old than in the 9-month-old group. A difference between groups in terms of postimmunisation antibody titres was observed only for rubella, with titres being significantly higher in the older group. Seroconversion rates were high in both groups and no serious events attributable to vaccination were observed. The MMR vaccine can thus be administered to children as young as 9 months of age. Evidence for the efficacy of a two-dose schedule, i.e. at 9 and 15 months, is presented.

A gE-negative bovine herpesvirus 1 (BHV1) vector vaccine carrying a gene coding for the G protein of bovine respiratory syncytial virus (BRSV) (BHV1/BRSV-G) induced the same high degree of protection in calves against BRSV infection and BHV1 infection as a multivalent commercial vaccine. A DNA plasmid vaccine, carrying the same gene as the BHV1/BRSV-G vaccine, significantly reduced BRSV shedding after BRSV infection compared with that in control calves, but less well than the BHV1/BRSV-G vaccine. Flow cytometric analysis showed a significant relative increase of gamma/delta+ T cells in peripheral blood after BRSV challenge-infection of the calves of the control group but not in the vaccinated groups. These results indicate that the G protein of BRSV can induce significant protection against BRSV infection in cattle, and that the BHV1/BRSV-G vaccine protects effectively against a subsequent BRSV and BHV1 infection.

In previous papers, we have shown that Escherichia coli heat-labile enterotoxin B subunit, supplemented with a trace amount of the holotoxin (LTB*) could be used as a potent adjuvant for a nasal influenza HA (haemagglutinin) vaccine in humans. The present study was designed to determine whether the effectiveness of a combined LTB*-HA vaccine could be limited by preexisting immunity to LTB and how many times the adjuvant-combined vaccine could be administered intranasally without reducing its protective efficacy in BALB/c, C3H and B10 mice. The magnitude of both nasal and serum Ab responses to HA vaccine was correlated with the degree of protection against virus infection. Higher doses of LTB*-combined vaccine were required for inducing high enough levels of anti-HA Ab responses to provide complete protection in low responder mice. Repeated pretreatments with LTB* alone (more than six times), which provided high levels of preexisting Abs to LTB, inhibited the induction of anti-HA Ab responses and reduced the protective efficacy of the adjuvant-combined vaccine. However, the LTB*-combined vaccine could be given repeatedly (about ten times) to mice without reducing the effectiveness of the adjuvant-combined vaccine. These results suggest that the LTB*-combined nasal influenza vaccine can be given to humans once every few years when an epidemic of influenza may occur.

Infection with Bordetella pertussis continues to result in widespread morbidity and mortality. Although whole cell pertussis vaccines are effective in controlling pertussis, concerns relating to adverse effects following vaccination have led to the development of a new generation of pertussis vaccines. Acellular pertussis vaccines have decreased endotoxin content and are less reactogenic than whole cell vaccines. The composition of acellular pertussis vaccines varies, resulting in differing immunogenicity. Recent studies have demonstrated that these vaccines, in general, have an efficacy similar to that of whole cell vaccines. The development of acellular pertussis vaccines is an advance that should result in less discomfort from vaccination and the potential for increased vaccine usage, resulting in the possible elimination of this disease.

Kauai physicians and District Health Office staff established a computerized tracking system in 1993 to improve immunization rates in Kauai-born infants. Comparison of 1995 and 1996 audit results of 1993- and 1994-born children showed completion rates for 9 antigens rose from 76% to 86%. Evolution and improvement of the tracking system are discussed. Recommendations for physicians are offered.

Background: Measles-mumps-rubella immunization rates among young children depend on the awareness and responsibility of parents and physicians. In order to improve immunization programmes, it is important to enhance our knowledge about attitudes of physicians in regard to MMR immunization. A random sample of 1013 general practitioners was interviewed by telephone in December 1994, with the collaboration of the BVA Institute. The large majority of French physicians (86%) have a favourable opinion about MMR immunization that they systematically propose to each child aged 12-24 months. However, barriers remain among some physicans. Favourable opinion about MMR immunization to infants was less frequent among physicians aged 41-50 years, homeopaths, those practicing in Southern France, those asking for higher payment to patients, those who are treating a small proportion of patients receiving public medical aid, those not convinced about the role of physicians in health education, those who experienced side-effects of immunization and those who are not personnally immunized against hepatitis B. Eradication of measles, mumps and rubella in France will be only achieved through a stronger and well-argumented information of physicians supported by health professional organizations.

The treatment of 17 patients having chronic obstructive bronchitis with a combined vaccine resulted in a rise in the number of T lymphocytes and T suppressors, as well as a simultaneous increase in their functional activity, in these patients. Moreover, an increase in the ingestive activity of neutrophils and in the concentration of immune complexes was registered. Treatment with the vaccine containing Staphylococcus aureus, Klebsiella pneumoniae, Proteus and Escherichia coli antigens facilitated an increase in the titers of antibodies to most antigens contained in the vaccine and in the resistance of the body to infection. Vaccinal therapy made it possible to achieve a significant prolongation of the period of remission.

Background: Because of concern about safety and efficacy, no pertussis vaccine has been included in the vaccination program in Sweden since 1979. To provide data that might permit the reintroduction of a pertussis vaccine, we conducted a placebo-controlled trial of two acellular and one whole-cell pertussis vaccines., Methods: After informed consent was obtained, 9829 children born in 1992 were randomly assigned to receive one of four vaccines: a two-component acellular diphtheria-tetanus-pertussis (DTP) vaccine (2566 children), a five-component acellular DTP vaccine (2587 children), a whole-cell DTP vaccine licensed in the United States (2102 children), or (as a control) a vaccine containing diphtheria and tetanus toxoids (DT) alone (2574 children). The vaccines were given at 2, 4, and 6 months of age, and the children were then followed for signs of pertussis for an additional 2 years (to a mean age of 21/2 years)., Results: The whole-cell vaccine was associated with significantly higher rates of protracted crying, cyanosis, fever, and local reactions than the other three vaccines. The rates of adverse events were similar for the acellular vaccines and the control DT vaccine. After three doses, the efficacy of the vaccines with respect to pertussis linked to a laboratory-confirmed case of pertussis or contact with an infected household member with paroxysmal cough for > or = 21 days was 58.9 percent for the two-component vaccine (95 percent confidence interval, 50.9 to 65.9 percent), 85.2 percent for the five-component vaccine (95 percent confidence interval, 80.6 to 88.8 percent), and 48.3 percent for the whole-cell vaccine (95 percent confidence interval, 37.0 to 57.6 percent)., Conclusions: The five-component acellular pertussis vaccine we evaluated can be recommended for general use, since it has a favorable safety profile and confers sustained protection against pertussis. The two-component acellular vaccine and the whole-cell vaccine were less efficacious.

Background: Concern about both safety and efficacy has made the use of whole-cell pertussis vaccines controversial. In some European countries, including Italy, the rate of vaccination against pertussis is low., Methods: We conducted a double-blind trial in Italy in which infants were randomly assigned to vaccination at two, four, and six months of age with an acellular pertussis vaccine together with diphtheria and tetanus toxoids (DTP); a DTP vaccine containing whole-cell pertussis (manufactured by Connaught Laboratories); or diphtheria and tetanus toxoids without pertussis (DT). The acellular DTP vaccine was either one containing filamentous hemagglutinin, pertactin, and pertussis toxin inactivated with formalin and glutaraldehyde (SmithKline Beecham) or one with filamentous hemagglutinin, pertactin, and genetically detoxified pertussis toxin (Chiron Biocine). Pertussis was defined as 21 days or more of paroxysmal cough, with infection confirmed by culture or serologic testing., Results: The efficacy of each vaccine, given in three doses, against pertussis was determined for 14,751 children over an average of 17 months, with cases included in the analysis if cough began 30 days or more after the completion of immunization. For both of the acellular DTP vaccines, the efficacy was 84 percent (95 percent confidence intervals, 76 to 89 percent for Biocine DTP and 76 to 90 percent for SmithKline DTP), whereas the efficacy of the whole-cell DTP vaccine was only 36 percent (95 percent confidence interval, 14 to 52 percent). The antibody responses were greater to the acellular vaccines than to the whole-cell vaccine. Local and systemic adverse events were significantly more frequent after the administration of the whole-cell vaccine. For the acellular vaccines, the frequency of adverse events was similar to that in the control (DT) group., Conclusions: The two acellular DTP vaccines we studied were safe, immunogenic, and efficacious against pertussis, whereas the efficacy of the whole-cell DTP vaccine was unexpectedly low.

The levels of antibody against measles, mumps, and rubella were determined at 5-6 years postimmunization in 468 children vaccinated with two different trivalent vaccines. The proportions of children without detectable antibody levels were 12 and 3.6% for measles (p < 0.001), 14.9 and 7% for mumps (p = 0.006), and 3.3 and 3.1% for rubella (p = 0.88), respectively, in MMR II and Trivirix recipients. A higher proportion of those vaccinated at younger ages had undetectable or low levels of measles antibody. These data indicate that a large proportion of children vaccinated under routine conditions do not have detectable measles and mumps antibody.

A two-dose vaccination program against measles, mumps, and rubella (MMR) viruses was started in Finland in 1982. In this program the trivalent MMR-II vaccine (MSD, USA) was offered to children at the ages of 14-18 months and 6 years followed by revaccination 4-5 years later. The vaccination coverage has been high (97%) and MMR infections have practically been eliminated in the Finnish population. In a serological follow-up program sequential serum samples were obtained from 254 children (127 14-18-month-old vaccinees and 127 6-year-old vaccinees) during a 9-year follow-up period. Anti-mumps virus antibody titers were determined by enzyme immunoassay using purified whole mumps viruses as the antigen. In seronegative (n = 120) 14-18-month-old vaccinees the seroconversion rate was 86% (geometric mean titer 1/1670 +/- 1/270). The antibody levels fell rapidly (significance p < 0.01) within the first year of follow-up (mean titer 1/1080 +/- 1/190), but remained relatively stable in subsequent years. After revaccination the seropositivity rate was 95% (mean titer 1/2310 +/- 1/260) and declined more slowly thereafter to 86% (mean titer 1/1510 +/- 1/210) at year 9 of follow-up. The mean antibody titer was significantly (p < 0.05) higher 4 years after the second MMR vaccination when compared with the corresponding time point after the first vaccination. In 6-year-old seronegative vaccinees the increase and decay of anti-mumps virus antibodies after the first MMR vaccination was similar to that seen in the group of younger vaccinees. A two-dose MMR vaccination protocol resulted in a high mumps immunity level in the vaccinated population.

Background: Although many whole-cell vaccines have been effective in preventing pertussis, these vaccines are difficult to standardize and can produce side effects. In Sweden, pertussis became endemic during the 1970s despite vaccination. Because of its limited efficacy, the Swedish-made whole-cell vaccine was withdrawn in 1979., Methods: To evaluate the efficacy of an acellular vaccine consisting of pertussis toxin inactivated by hydrogen peroxide (pertussis toxoid), we conducted a randomized, double-blind, placebo-controlled trial in Sweden. Infants were vaccinated with either diphtheria and tetanus toxoids alone (DT toxoids, 1726 infants) or diphtheria, tetanus, and pertussis toxoids (DTP toxoids, 1724 infants) at 3, 5, and 12 months of age., Results: There were no serious reactions. With the pertussis vaccine there were slightly more local reactions than with the DT toxoids alone, but the rates of postvaccination fever were the same. The main period of surveillance, which began 30 days after the third vaccination, continued for a median of 17.5 months. There were 312 cases of pertussis (72 in the DTP-toxoids group and 240 in the DT-toxoids group) that met the clinical criterion (paroxysmal cough lasting > or = 21 days) and laboratory criteria for pertussis as defined by the World Health Organization. The efficacy of this acellular vaccine was 71 percent (95 percent confidence interval, 63 to 78 percent). The recipients of DTP toxoids who had pertussis had cough of shorter duration than the recipients of DT toxoids, and fewer had whooping and vomiting. The vaccine efficacy after two doses was 55 percent (95 percent confidence interval, 12 to 78 percent), on the basis of 14 cases in the DTP-toxoids group and 31 in the DT-toxoids group that met the definition of the World Health Organization., Conclusions: A pharmacologically inert, acellular pertussis-toxoid vaccine that is easily standardized is safe and confers substantial protection against pertussis.

Diphtheria and tetanus antibody levels were measured before and four weeks after booster vaccination of 313 Danish military recruits participating in a clinical trial to compare aluminium hydroxide and calcium phosphate as adjuvants in diphtheria-tetanus vaccines (DT). Twenty-eight percent of the men had a diphtheria pre-vaccination content below a protective level of 0.01 IU ml-1. The calcium phosphate adsorbed vaccine showed the highest efficacy for both antigens. Adverse reactions were rare but more frequent in the calcium group than in the aluminium group. No correlation was found between pre- or post-vaccination levels and adverse reactions and both vaccines gave rise to specific IgE formation. The results show that calcium phosphate is more effective but not a safer alternative to aluminium hydroxide when compared in vaccines containing 1.0 mg ml-1 of Ca or of Al.

Objective: Following the introduction of a national measles and subsequent MMR vaccination programme, to determine the susceptibility of 3-14-year-old children to measles, mumps and rubella and to relate the results to the epidemiology of measles and the need for vaccination policy changes., Design: Cross-sectional sero-survey and trends in measles notifications and mortality., Setting: Paediatric hospital outpatient departments in Dublin., Subjects: Sera were collected from 837 children attending the clinics in 1991 and 1992., Results: The prevalence of antibodies in children aged 3-6, 7-10 and 11-14 years was 84, 83 and 95% for measles; 48, 60 and 65% for mumps; and 78, 63 and 74% for rubella, respectively. The prevalence of mumps antibodies may be underestimated. Ninety-six per cent of girls aged 13-14 years had rubella antibodies. A widespread outbreak of measles occurred in 1993. Over recent years, an increasing proportion of measles notifications were in older children., Conclusion: Given sub-optimal uptake of MMR vaccine, outbreaks of infection in pre- and primary school children are inevitable. In such circumstances, a 2-shot MMR vaccine programme with high uptake is essential to prevent a shift of disease into older age groups.

Background: In a Phase II trial, surgical adjuvant active specific immunotherapy using a live vaccinia virus-augmented allogeneic polyvalent melanoma cell lysate, vaccinia melanoma oncolysate (VMO), produced a significant disease free interval (DFI) in patients with International Union Against Cancer Stage II melanoma with positive lymph nodes. Therefore, a Phase III randomized prospective, double-blind, multiinstitutional, surgical adjuvant VMO trial was performed to determine the efficacy of VMO to increase the DFI and the overall survival in this group of patients with Stage II disease., Methods: Two hundred and fifty patients with Stage II melanoma were divided into two postsurgical groups. One group received VMO (total protein equals 2 mg/ml) and the other received the placebo of live vaccinia vaccine virus (V) (10(5.4) TCID50/ml), an adjuvant component of the VMO. Patients initially received these biologics once a week for 13 weeks and then once every 2 weeks for an additional 39 weeks or until recurrence. All surviving patients have been followed for at least 30 months., Results: Statistical analysis of survival data (n = 217) for this first interim analysis shows that there is no statistically significant (P = 0.99) increase in DFI of patients treated with VMO (n = 104) when compared with V (n = 113). The median DFI is 38.0 months for patients treated with VMO and 37.0 months for patients treated with V. At 2- and 4-year intervals, 70 and 38%, respectively, of patients treated with VMO vs. 66 and 36%, respectively, of patients treated with V were free of melanoma. The median overall survival is not available because the patients treated with VMO have not yet reached the 50% mark and the median overall survival is 45.0 months for patients treated with V. At 2- and 4-year intervals, 70 and 38%, respectively, of VMO-treated patients survived when compared with 66 and 36%, respectively, of patients treated with V. Although the overall survival of patients treated with VMO is not statistically significant (P = 0.88) at this point, there is an increasing trend in the overall survival of patients treated with VMO; a 10% increase at the 4-year time point. Moreover, in the subset analysis, VMO-treated male patients (n = 63) showed a 17% improvement in survival at 4-year time point when compared with male patients treated with V (n = 67) (P = 0.19) at the same time point and male patients (n = 20) between the ages of 44 and 57 having 1-5 positive lymph nodes showed a 37% difference in overall survival at the 4-year time point when compared with those patients treated with V (n = 18) (P = 0.13) at the same time point., Conclusion: In this first interim analysis, active specific immunotherapy with VMO vs. V showed no difference in the disease free interval or overall survival. Subset analyses likewise showed no significant differences in outcome but the data suggest a potential difference in immunoreactivity between male and female patients with melanoma that awaits further follow up and may merit further investigation.

An outbreak of 18 cases of measles in a primary school in the Australian Capital Territory in August and September 1993 provided the opportunity to study measles immunisation status and measles vaccine efficacy. Parents of 384 (78 per cent) of 491 children answered a questionnaire on recent illness consistent with measles and measles immunisation. Parents transcribed details of measles immunisation from the personal health record of the child to the questionnaire. Thirty-three per cent of cases and 3.4 per cent of the other children had not been immunised. Overall, 95 per cent of children had been immunised. The efficacy for all measles vaccines was estimated to be 90 per cent (95 per cent confidence interval (CI) 75 to 96) and for measles-mumps vaccine 87 per cent (CI 70 to 95). All of the immunised cases had received measles-mumps vaccine. There was no increased risk of measles infection in those who had been immunised at under 15 months of age compared with those immunised at 15 months or older, or in those who could not provide a date of immunisation compared with those who could. None of the children who had received two doses of vaccine caught measles. The date of immunisation was provided by 65 per cent of the respondents who said their children had been immunised. Asking parents to provide this date instead of viewing the health record is a less expensive way of assessing immunisation status but this method needs to be evaluated. Measles outbreaks still occur in highly immunised populations when vaccine efficacy appears to be acceptable.

In two groups of 25 urological patients each, with and free of urinary infection, Urostim is administered fifteen days before and after the operation. The prophylactic effect of the drug in terms of hospital transmitted wound and urinary infections is recorded on the basis of comparative study with control groups. As shown by the results obtained, Urostim immunoprophylaxis yields positive results in urological practice. In 80 per cent of the cases development of the complication is prevented. Vaccine administration in conjunction with an updated antibiotic broadens the therapeutic scope in patients with urinary infection.