To investigate the incorporation of oral rhesus-human reassortant rotavirus tetravalent (RRV-TV) vaccine into a routine immunization programme, RRV-TV or oral placebo was coadministered with a pentavalent diphtheria-tetanus-whole-cell pertussis-Haemophilus influenzae b (Hib)-inactivated polio vaccine and hepatitis B vaccine following a 3-4-5-mo schedule in a double-blind trial involving 249 infants. Seroconversion rates after 3 doses of rotavirus vaccine were 80% for rotavirus immunoglobulin A (IgA) and 93% for RRV neutralizing antibodies. Rotavirus vaccine did not interfere with the immune responses to diphtheria, tetanus, pertussis, Hib, poliovirus 1, 2 and 3, or hepatitis B. Following the first, second and third doses of vaccine, fever >38 degrees C on the day of vaccination was seen in 31%, 24% and 24%, respectively, with no difference between RRV-TV- and placebo-vaccinated children. This fever was presumably due to the whole-cell pertussis vaccine. Those vaccinees who received concomitant RRV-TV vaccine had another peak of fever around d 4 after the first dose, when 25% of them had fever >38 degrees C and 3% >39 degrees C. It is concluded that RRV-TV rotavirus vaccine can be given concurrently with other childhood immunizations following a 3-4-5-mo vaccination schedule. However, febrile reactions to RRV-TV rotavirus vaccine are common when the first dose is given at the age of 3 mo.

Background: A quadrivalent meningococcal diphtheria conjugate vaccine (MCV-4) has been developed to provide T-cell dependent immune responses against 4 major disease-causing serogroups (A, C, Y, W-135). Methods: In a comparative, randomized, modified double blind, controlled study in healthy 2- to 10-year-old U.S. children, safety and immunogenicity profiles of MCV-4 (n = 696) were compared with those of a licensed quadrivalent polysaccharide vaccine, Menomune A/C/Y/W-135 (PSV-4, n = 702). Vaccine-related adverse reactions were assessed for 28-day and 6-month follow-up periods. Serum bactericidal activity (SBA) was assayed in prevaccination, day 28 and 6-month postvaccination sera samples. Results: Both vaccines were well-tolerated, with no vaccine-related serious adverse events and similar rates of mostly mild local and systemic reactions. Functional antibody (SBA) seroconversion percentages were significantly higher for all 4 serogroups in the MCV-4 group. The SBA geometric mean titers against serogroups A, C, Y and W-135 with MCV-4 were 1700, 354, 637 and 750, respectively, compared with PSV-4 (893, 231, 408 and 426) 28 days postvaccination (P < 0.001 for all comparisons). This significant difference persisted through 6 months. Conclusions: In 2- to 10-year-old children MCV-4 had a safety profile similar to that of PSV-4 and elicited significantly higher and more persistent serum bactericidal antibody responses against meningococcal serogroups A, C, Y and W-135 than did the licensed polysaccharide vaccine. Copyright © 2005 by Lippincott Williams & Wilkins.

The immunogenicity of RIX4414 (Rotarix™) co-administered with DTPa-combined vaccines (Infanrix hexa™ and Infanrix™ Polio Hib) was evaluated in a double-blind, randomized, placebo-controlled, phase III trial (102247) in Europe.

OBJECTIVE:

To determine the safety and immunogenicity of childhood vaccines in children with perinatally acquired human immunodeficiency virus type 1 (HIV-1) infection.

DESIGN:

Nonrandomized, prospective cohort study; 12-month follow-up period.

SETTING:

Obstetric wards and outpatient pediatric clinics at two large hospitals in Kinshasa, Zaire.

PATIENTS:

A total of 8108 pregnant women were screened for HIV-1 antibodies. The 474 children born to 466 seropositive women identified during screening and the 616 children born to 606 seronegative, age- and parity-matched women were vaccinated.

INTERVENTION:

The following vaccines were administered at the stated ages: bacille Calmette-Guérin (BCG) vaccine (2 days); trivalent oral Sabin poliomyelitis vaccine (2 days and 6, 10, and 14 weeks); and adsorbed diphtheria-tetanus-pertussis (DTP) vaccine (6, 10, and 14 weeks).

MEASUREMENTS AND MAIN RESULTS:

Protective antibody titers to tetanus and poliovirus types 1, 2, and 3 were achieved in 95% of all children. Among children with HIV-1 infection, 70.8% had protective antibody titers to diphtheria compared with 98.5% of uninfected children (p < 0.05). Geometric mean antibody titers to diphtheria and poliovirus types 1, 2, and 3 were significantly lower in children with HIV-1 infection than in uninfected children. Vaccine-associated side effects were similarly low in all children.

CONCLUSIONS:

The low incidence of side effects and the high proportion of children with HIV-1 infection who achieved protective postimmunization antibody titers support the continuing use of BCG, DTP, and oral polio vaccines in childhood immunization programs in HIV-1 endemic areas.

OBJECTIVE:

The aim of this open, multicenter, randomized trial was to evaluate the immunogenicity and reactogenicity of a candidate combined diphtheria-tetanus-acellular pertussis-hepatitis B virus-inactivated polio virus (DTaP-HBV-IPV) vaccine when given as either a mixed or as separate concomitant injections with Haemophilus influenzae type b (Hib) vaccine.

STUDY DESIGN:

A total of 359 subjects were randomized to receive either DTaP-HBV-IPV/Hib (mixed administration - 180 subjects) or DTaP-HBV-IPV + Hib (separate administration in opposite limbs - 179 subjects) at 2, 3, and 4 months of age.

RESULTS:

After vaccination, seroprotective antibody concentrations against diphtheria, tetanus, hepatitis B, and polio viruses and a high (> or = 97%) pertussis vaccine response were seen in almost all study participants. All subjects except one in the mixed administration group had postvaccination Hib anti-PRP antibody concentrations > or = 0.15 microg/mL. Of subjects in the mixed and separate group, 77.2% (geometric mean antibody concentration, 2. 62 microg/mL) and 88.6% (geometric mean antibody concentration, 4.45 microg/mL) had Hib anti-PRP concentrations > or = 1 microg/mL, respectively. The addition of the Hib component to the 5-component vaccine did not increase the incidence of local or general reactions.

CONCLUSION:

Both administrations of the candidate vaccine were found to be safe, immunogenic, and well tolerated. Although anti-PRP geometric mean antibody concentrations and the percent of subjects achieving the 1 microg/mL seroprotective level were lower after the mixed administration, they were in the range seen with monovalent Hib vaccines or with other DTaP-based/Hib combinations licensed in some European countries. Therefore both administrations have the potential to simplify childhood immunization.

We compared an acellular (B type) pertussis-component diphtheria-tetanus-pertussis (DTP-Ac) vaccine containing equal amounts of filamentous hemagglutinin and lymphocytosis-promoting factor with a conventional whole-cell vaccine as the first booster immunization in 162 healthy children 15 to 24 months of age. Fewer local reactions (e.g., erythema, swelling, and tenderness at the injection site) were seen in DTP-Ac vaccine recipients during the first 48 hours of observation. This group also had fewer episodes of fever (> or = 38 degrees C) and other systemic reactions (e.g., irritability, drowsiness, and anorexia). Overall, 57% of the DTP-Ac vaccine recipients had no obvious adverse reactions, in contrast to 5% in the comparison group. At 4 to 8 weeks after vaccination, serum antibody responses to filamentous hemagglutinin and lymphocytosis-promoting factor were greater in recipients of the acellular vaccine as determined by an enzyme-linked immunosorbent assay. We conclude that this B-type acellular vaccine is both immunogenic and much less likely to cause an adverse reaction than a currently licensed whole-cell vaccine, and is suitable for routine booster immunizing doses to protect against pertussis.

In two double-blind, randomized, comparative studies involving a total of 218 children, an acellular pertussis (DTPa) vaccine containing diphtheria and tetanus toxoids and pertussis components filamentous haemagglutinin (FHA), pertussis toxoid (PT), and 69 kDa outer membrane protein (69 kDa OMP) was administered as a booster to 17-month-old and 5-year-old children with a history of routine whole-cell diphtheria-tetanus-pertussis (DTPw) vaccination. The control groups in these studies received DTPw vaccine. Among 17-month-old toddlers, significantly lower proportions of DTPa vaccine recipients had local pain (7.3%), redness (14.5%) and swelling (9.1%) than DTPw vaccine recipients (23.6%, 30.9% and 23.6%, respectively). A trend toward fewer local reactions was also seen in 5-year-old children vaccinated with DTPa in private practice and public clinics although differences were not statistically significant. Fever (rectal temperature > or = 38 degrees C) was reported more frequently for DTPw vaccine recipients in both age groups. While no differences existed between groups in terms of geometric mean antibody titres (GMTs) prior to booster vaccination, anti-PT antibody GMTs were higher among DTPa vaccine recipients than among DTPw vaccine recipients after booster vaccination. The difference was statistically significant in 5-year-old subjects. Furthermore, significantly higher anti-FHA and anti-69 kDa OMP GMTs were seen in DTPa vaccine recipients in both age groups. In pre-vaccination seropositive subjects and in pre-vaccination seronegative subjects the rate of immune response to pertussis antigens was higher for DTPa than for DTPw vaccine recipients with the exception of the rate of response induced to 69 kDa OMP in 5-year-old children. The lower frequency of side-effects and similar or greater immunogenicity of DTPa vaccine when used as a booster in subjects primed with DTPw encourage the introduction of this type of vaccine for the fourth and fifth DTP doses that are routinely administered in many countries.

A DTaP-IPV//PRP-T combination vaccine (Pentacel) has been universally used in Canada to provide immunization against diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae type b with single injections at 2, 4, 6 and 18 months of age. This randomized, multicenter study was conducted to evaluate administration of a fourth dose of DTaP-IPV//PRP-T at 15 to 18 months of age, similar to the US immunization schedule. Participants who had received three doses of DTaP-IPV//PRP-T by 8 months of age were enrolled at 12 months and randomized to receive a fourth dose at 15, 16, 17 or 18 months. Antibody levels for each vaccine antigen were measured prior to and four weeks following booster vaccination. Overall, 1782 subjects were immunized and monitored for adverse events, and 735 were evaluated for immune responses. Preimmunization antibody levels differed minimally by age, for all antigens. The immune responses elicited by DTaP-IPV//PRP-T were comparable between participants vaccinated at 15 or 16 months and those vaccinated at 17 or 18 months, as demonstrated by specific antibody geometric mean titers, seroprotection/seroresponse rates, and reverse cumulative distribution curves. The fourth dose was well tolerated in all age groups. Toddlers at 15, 16, 17 or 18 months of age are equally suitable recipients for booster immunization with the DTaP-IPV//PRP-T vaccine.

BACKGROUND:

Meningococcal C disease can be life-threatening in infants, young children and adolescents. New conjugate vaccines are immunogenic in young infants and induce immunologic memory, so we should consider incorporating them into the routine childhood immunization program. The objective of this study was to measure the safety and immunogenicity of a meningococcal C conjugate vaccine when given with routine childhood vaccines.

METHODS:

We carried out a randomized, double-blind, controlled clinical trial at children's hospitals in 3 Canadian cities. A convenience sample of 351 healthy 2-month-old infants was enrolled from the community and randomly allocated to receive either meningococcal C conjugate vaccine or the control (hepatitis B) vaccine. All participants received a concurrent injection of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTaP-IPV-Hib) conjugate vaccine in the opposite limb. Participants were immunized at 2, 4, 6 and 15 months of age; adverse events were recorded after each dose. Serum bactericidal and ELISA meningococcal antibody levels in the participants were measured at 6, 7, 15 and 16 months of age; diphtheria, tetanus, H. influenzae type b, poliovirus and pertussis antibodies were measured at 7 months of age. A total of 323 (92%) participants completed all aspects of the study. The proportion of participants who suffered adverse events after each vaccine dose was the primary safety outcome. Geometric mean antibody titres and the proportion of participants with protective antibody levels after immunization were the primary immunologic outcomes.

RESULTS:

After 2 doses of the meningococcal C conjugate vaccine 99% of participants achieved a protective ( > or = 1:8) bactericidal meningococcal serogroup C antibody level, and after 3 doses this rate increased to 100%. Antibody levels to the concomitant vaccine antigens in the group receiving meningococcal C vaccine were similar to those in the control group except for higher antidiphtheria antibody titres (p < 0.001). Local injection site reactions (redness and induration) after the meningococcal conjugate vaccine were more frequent than after hepatitis B vaccine but less frequent than after the DTaP-IPV-Hib vaccine.

CONCLUSIONS:

The meningococcal C conjugate vaccine can be safely and effectively administered at the same visit as the other vaccine antigens routinely given to infants in Canada.

METHODS:

In an open randomized study we compared the safety and immunogenicity of two schedules for priming and booster vaccinations of infants. A pentavalent combination vaccine, including a lyophilized Haemophilus influenzae type b-tetanus toxoid conjugate vaccine reconstituted with a liquid diphtheria, tetanus, acellular pertussis (pertussis toxoid and filamentous hemagglutinin) and inactivated polio vaccine (DTaP-IPV/Act-HIB; Pasteur Mérieux Connaught, Lyon, France) was administered to 236 Swedish infants either at 2, 4 and 6 months or at 3 and 5 months, and a booster dose was administered 7 months after the last primary dose. Adverse events were monitored by diaries for 3 days after each vaccination and by questions at the ensuing visits. Antibodies against the different vaccine components were analyzed after the primary series of vaccinations, before and after the booster injections.

RESULTS:

There were no serious adverse reactions, and the rates of febrile events and local reactions were low in both groups. The three dose primary schedule induced higher geometricmean concentrations for all antigens than did the two dose schedule, but there were no differences between the groups in proportions with protective antibody titers against diphtheria, tetanus, Hib and polio or in proportions with certain defined levels of pertussis antibodies. Prebooster results showed a similar pattern, with the exception that the group primed with three injections showed higher proportions of infants with detectable antibodies against polio-virus types 1 and 3. After booster vaccinations there were no differences between the two schedules in geometric mean or in proportions with antibodies above defined antibody concentrations, indicating effective priming from both primary series of vaccinations. Conclusion. The combined vaccine DTaP-IPV/ Act-HIB vaccine was equally safe and immunogenic when administered according to both time schedules studied.