Immunogenicity of Haemophilus influenzae type b capsular polysaccharide vaccines in 18-month-old infants.

Haemophilus influenzae vaccine containing polyribosyl ribitol phosphate (PRP) or PRP covalently linked to diphtheria toxoid (PRP-D) was given to 94 healthy infants 17 to 22 months of age at the same time, but not at the same site, as a diphtheria-tetanus-pertussis booster. Systemic reactions were similar in the two vaccine groups and resembled those expected with the diphtheria-tetanus-pertussis injection alone. Six (13%) and seven (14%) of the PRP and PRP-D recipients, respectively, had minor local reactions to the Haemophilus vaccine. Among the 77 children who were not already naturally immune (ie, anti-PRP antibody concentration of less than or equal to 0.15 micrograms of protein per milliliter) before vaccination, PRP-D was significantly more effective than PRP in inducing protective levels of antibody. Only 15 (43%) of the 35 nonimmune PRP recipients achieved a concentration of greater than or equal to 0.15 microgram/mL and only seven (20%) reached a concentration greater than or equal to 1.0 micrograms/mL following vaccination. In contrast, 34 (81%) of the 42 nonimmune recipients of PRP-D had a concentration of greater than or equal to 0.15 microgram/mL following vaccine and 32 (62%) had a concentration of greater than or equal to 1.0 micrograms/mL (P less than or equal to .001). These results suggest that more than one-half of nonimmune 18-month-old infants will not respond to PRP with protective levels of antibody. In light of the current data, recommendation for revaccination at 24 months of age for those immunized at any younger age is appropriate.

Haemophilus influenzae type b immunization of children with sickle cell diseases.

Haemophilus influenzae type B vaccine is recommended for children 1.5 to 6 years of age with sickle cell anemia, but the adequacy of their response is unknown. A total of 69 children with sickle cell syndromes, 1.5 to 5.6 years of age, were immunized with two vaccines alternatively, single blind. PRP vaccine was given to 36 children and a diphtheria toxoid conjugated vaccine, PRP-D, was given to 36. Coded pre- and postvaccine sera were tested by radioimmunoassay for anti-PRP antibody. The groups did not differ in age distribution or type of sickle hemoglobinopathy. Preexisting antibody levels were low in both vaccine groups; 65% were less than 0.15 microgram/mL. The vaccines were safe but associated with frequent minor reactions. PRP-D gave higher geometric mean titers and mean fold titer increase than PRP in all children (15.58 micrograms/mL [234-fold] v 2.63 micrograms/mL [29-fold]) and in the subgroups 1.5 to 2.5 years of age or with pretiter values less than 0.15 microgram/mL. Titers for 64% of children receiving PRP and 94% receiving PRP-D were greater than or equal to 1.0 microgram/mL. Thus, both vaccines were useful in this population, but PRP-D was more immunogenic. Duration of antibody levels postvaccination, booster responses, and PRP-D immunogenicity in younger children with sickle cell syndromes all require further study.

Capsular polysaccharide Haemophilus influenzae type b vaccine: clinical and immunologic responses to two vaccines.

The clinical reactions and immunologic responses to two Haemophilus influenzae type b capsular polysaccharide vaccines were studied in 24- to 36-month-old children. A candidate vaccine (Connaught) induced greater than or equal to 1.0 microgram/ml of antipolysaccharide antibody in 37 (61.7%) of 60 infants 24 to 26 months of age; this compared with 8 (38.1%) of 21 infants 24 to 36 months of age given a licensed vaccine (Praxis). Reactions to both vaccines within 24 hours of administration were minimal; a smaller percentage of recipients of the candidate vaccine were asymptomatic (P less than 0.05). The lower levels of antibody production than previously reported may necessitate a reevaluation of current recommendations.

An accurate photographic method for grading acne: initial use in a double-blind clinical comparison of minocycline and tetracycline.

This investigation utilized an accurate photographic method and grading scale for evaluating acne in sixty-two patients. During a randomized double-blind clinical study in which half of the patients received minocycline and half, tetracycline, photographs of facial or body acne were taken at baseline and every 2 weeks over a 12-week period of therapy. In addition to on-site blinded gradings by both the investigator and the patients, separate assessments were made by two independent dermatologists utilizing the scale and the transparencies taken during the study. A reasonable agreement was found between the investigator, the patients, and the independent dermatologists, indicating the usefulness of this method. The investigator's rating of acne severity disclosed a significantly (p less than or equal to 0.05) more rapid clinical response at weeks 2 and 8 in the patients who received minocycline than in those who received tetracycline. Also, the assessment of one of the independent dermatologists showed a significantly (p = 0.024) better response to minocycline than to tetracycline at week 8 of therapy. The incidence of adverse clinical experiences was lower in the minocycline-treated group (10%) than in the tetracycline-treated group (22%).

Pediatric diphtheria and tetanus toxoids-adsorbed vaccine: immune response to the first booster following the diphtheria and tetanus toxoids vaccine primary series.

Diphtheria and tetanus toxoids (DT) vaccine should be given to children at 2, 4 and 6 months of age when there are contraindications to the administration of pertussis vaccine. We have previously reported that such children develop protective antitoxin antibody levels to diphtheria and tetanus antigens. This follow-up study evaluates the decay in antitoxin antibody levels and the booster response elicited to DT antigen when a fourth dose is given at approximately 18 months of age. Twenty-three children receiving DT vaccine were compared to 38 receiving diphtheria and tetanus toxoids-pertussis (DTP) vaccine. The prebooster antibody titer to diphtheria and tetanus at approximately 18 months of age had declined below the recommended protective level in one child who had received DT vaccine and in three children who had received DTP. Following the 18-month booster dose of DT and DTP vaccine, all of the children had protective titers to diphtheria and tetanus toxin. These results suggest that the adjuvant effects of pertussis vaccine are not required to achieve adequate immunization to diphtheria and tetanus when currently available DT vaccine is used in early childhood.

Safety and immunogenicity of Haemophilus influenzae type b-polysaccharide diphtheria toxoid conjugate vaccine in infants 9 to 15 months of age.

Sixty 9- to 15-month-old infants were randomly assigned to receive two doses, 1 month apart, of a Haemophilus influenzae type b capsular polysaccharide-diphtheria toxoid conjugate vaccine (PRP-D) or PRP vaccine, each containing 20 micrograms PRP. There were no significant local or systemic reactions. After one dose of PRP-D, 93% of the subjects attained levels of greater than or equal to 0.15 microgram/ml and 59% achieved greater than or equal to 1 microgram/ml antibody protein. These percentages rose to 100% and 86%, respectively, after the second dose, at which time the geometric mean titer of anti-PRP antibody was 4.8 micrograms/ml. IgG anti-PRP levels were 4.3 times higher than IgM. The proportion of IgG to IgM antibody induced by PRP-D increased with age. After two doses, 33% of the PRP recipients responded with a level of greater than or equal to 0.15 microgram/ml and only 19% responded to a level of greater than or equal to 1.0 microgram/ml. One year later, all of the PRP-D recipients tested still had greater than or equal to 0.15 microgram/ml and more than half had greater than or equal to 1.0 microgram/ml antibody protein.

Diphtheria and tetanus toxoids and pertussis vaccine adsorbed (DTP): response to varying immunizing dosage and schedule.

In developing guidelines for the optimal schedule of DTP vaccine administration, it is imperative to explore alternative regimens to the current U.S. primary series of DTP vaccine at two, four, and six months and a booster at 18 months of age. Two approaches to primary immunization that reduce the total number of pertussis mouse protective units administered were studied in an effort to reduce adverse reactions. A modified, reduced (0.25 ml) dosage of each inoculation of DTP vaccine was compared with the usual immunization schedule. The reduced dosage group had consistently fewer adverse reactions with a significant reduction in febrile reactions and acute behavioural changes during the primary series at two, four, and six months and the booster at 18 months and fewer local reactions noted during the primary series (p less than 0.05). Geometric mean titers of pertussis agglutinins were higher after the primary series in vaccine recipients immunized with the recommended schedule but were similar in the two study groups before and after the 18 month immunization. An alternative approach studied the response following the administration of only two DTP immunizations of 0.5 ml, using a number of schedules to determine if lengthening the interval between the first and second pertussis inoculation would enhance the response to the pertussis antigen. Irrespective of whether the DTP vaccine was the first, second, or third of the primary series, the adverse reactions were similar. After the second DTP immunization, little difference was noted in the serologic response to pertussis. All agglutinin titers were significantly lower than that achieved after three standard doses of DTP vaccine (p less than 0.01).

Safety and immunogenicity of Haemophilus influenzae type B polysaccharide-diphtheria toxoid conjugate vaccine in adults.

Sixty-one adults received either Haemophilus influenzae type b capsular polyribosephosphate (PRP) vaccine or H. influenzae type b polysaccharide-diphtheria toxoid conjugate (PRP-D) vaccine in two doses, one month apart. Both vaccines were well tolerated with no fever or systemic reactions. There were no significant local reactions. Mild local tenderness was reported by about half of the subjects in both groups. There was no observed effect of the vaccines on hematologic parameters, including reticulocyte and platelet counts, evaluated before immunization, one month after the first dose, and seven to 10 days after the second dose. A single dose of PRP-D induced levels of IgG antibody to PRP three times that observed with PRP alone one month after the first inoculation.

DTP reactions and serologic response with a reduced dose schedule.

In a double-blind study, infants received standard (0.5 ml) or modified (0.25 ml) doses of DTP vaccine for the primary series of three immunizations administered at 2, 4, and 6 months of age and the booster immunization at 18 months. Side effects and antibody responses were determined in 80 children who completed the primary series and 73 who received the booster. The modified regimen was associated with significantly reduced febrile reactions and behavioral changes after the primary series and booster inoculation: 63.2% of those who received the standard dose had febrile reactions, compared to 42.3% who received the modified dose during the primary series; a similar difference was observed with the booster. Only 47.2% of the reduced dosage recipients demonstrated marked behavioral changes, and 62.4% of the standard vaccine recipients had comparable reactions. An even larger difference (33.3% vs 64.7%) was noted at the time of the booster. The modified vaccine produced a local reaction incidence of 58.5%, compared to 72.6% in the control population during the primary immunization series; no differences were noted in local reactions with the booster dose. All patients had serologic evidence of protective titers against diphtheria and tetanus. After the primary immunization series, 97.6% and 97.3% of the infants given the modified and standard doses, respectively, had pertussis agglutinin titers of greater than or equal to 1:16. One patient who received the standard dosage had a titer of less than 1:16 one month after the booster immunization, whereas all those given the modified dose had titers greater than or equal to 1:16. Geometric mean titers of pertussis agglutinins were higher in the standard vaccine recipients after the primary series, but were similar in the two study groups before and after the 18-month immunization.

Primary immunization with diphtheria-tetanus toxoids vaccine and diphtheria-tetanus toxoids-pertussis vaccine adsorbed: comparison of schedules.

In a double blind study patients were randomly divided into two groups. All patients received an initial immunization with diphtheria-tetanus toxoids-pertussis (DTP) vaccine at 2 months of age. One population received diphtheria-tetanus toxoids (DT pediatric) vaccine at the time of the second immunization at 4 months of age and DTP vaccine at 6 months (DTP-DT-DTP). In a second group DTP vaccine was administered as the second immunization and DT (pediatric) vaccine was given at the 6-month visit (DTP-DTP-DT). There was a significantly increased incidence and severity of adverse reactions associated with DTP vaccine when contrasted with responses observed after DT vaccine; differences were apparent whether the vaccine was administered as the second or the third immunization. All patients had serologic evidence of protection to diphtheria and tetanus following completion of either primary series. The geometric mean titer of pertussis agglutinins was similar in the two study groups 2 months after the second DTP immunization but was significantly higher in the DTP-DT-DTP group at 1 to 2 months after the completion of the primary immunization series (P less than 0.01). Both groups, however, were significantly lower than the comparable geometric mean titer measured after a series of three DTP inoculations (7.51, log2) (P less than 0.01). This study supports the recommendation that three immunizations of DTP be administered in the first year of life.

Immunogenicity in infants of a vaccine composed of Haemophilus influenzae type b capsular polysaccharide mixed with DPT or conjugated to diphtheria toxoid.

Fifty-three healthy infants received either Haemophilus influenzae type b capsular polysaccharide (PRP) mixed with diphtheria-pertussis-tetanus vaccine (DPT) or PRP conjugated covalently to diphtheria toxoid (PRP-D). The immunizations were given at 3, 5, 7, and either 14 or 18 months of age and were well tolerated. The geometric mean titers of antibody to PRP at eight months of age (after the first immunizations) were 0.26 micrograms/ml in the PRP + DPT group and 1.56 micrograms/ml in the PRP-D group. After the fourth dose, an IgG response was seen in both groups. The PRP + DPT group had a geometric mean level of antibody to PRP of 3.98 micrograms/ml at 19 months and the PRP-D group, 31.22 or 24.00 micrograms/ml at 15 or 19 months, respectively. Compared with previously published data of children immunized with one dose of PRP at 18 months, the mean level of antibody to PRP in the PRP-D group at 19 months was significantly (P less than .001) higher, whereas that in the PRP + DPT group was not.

Efficacy of Haemophilus influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine in infancy.

Haemophilus influenzae type b capsular polysaccharide-diphtheria toxoid conjugate vaccine has recently been shown to be capable of inducing antibodies to H. influenzae in infants. In an evaluation of its clinical efficacy, 60,000 children were enrolled in an open trial in Finland. Children born on odd-numbered days between October 1, 1985, and September 30, 1986, received the vaccine at 3, 4, 6, and 14 months; those born on even-numbered days served as controls. The geometric mean antibody titer measured in a cohort of 99 children rose from a prevaccination level of 0.08 microgram per milliliter at three months of age to 0.42 microgram per milliliter at seven months. Only minor adverse reactions were reported. Up to February 1987, two cases of invasive H. influenzae infection had occurred among the children who had received three doses of vaccine, whereas 12 cases had occurred among the controls (P = 0.0005 by Poisson one-tailed test). The rate of short-term (average follow-up time, five months) protection provided by this conjugate vaccine in infancy was thus 83 percent.