Patrick McVerry

Haemophilus influenzae diphtheria protein conjugate immunization after therapy in splenectomized patients with Hodgkin disease.

Excerpt Patients with Hodgkin disease are at risk for life-threateningHaemophilus influenzaeinfections (1, 2). Splenectomy interferes with opsonization and phagocytosis of encapsulated bacteria (3)...

Vaccination of 18-month-old children with conjugated polyribosyl ribitol phosphate stimulates production of functional antibody to Haemophilus influenzae type b.

Eighteen-month-old children were immunized with polyribosyl ribitol phosphate (PRP) of Haemophilus influenzae type b or with PRP that had been conjugated to diphtheria toxoid. Conjugated vaccine stimulated significant mean increases in antibody titer as measured by radioimmunoassay and bactericidal effect, as well as a modest increase in opsonizing activity. In contrast unconjugated vaccine caused lesser albeit significant rises in antibody titer, but a negligible antibacterial effect. These results suggest that vaccinating infants with conjugated PRP is more likely to stimulate production of antibodies that are protective against systemic infection caused by H. influenzae type b than vaccinating with unconjugated PRP.

H. INFLUENZA B IMMUNIZATION OF CHILDREN WITH SICKLE CELL DISEASES

H. flu B vaccine is recommended for children 1.5-6 yrs with sickle cell anemia but the adequacy of their response is unknown. We immunized 55 children age 1.5-5.6 yrs (mean 3.6) with sickle cell syndromes, ss, sc or s-thal using two vaccines alternately, single blind (25 patients PRP; 30 PRP-D). The vaccine groups were similar in age, sickle diagnoses and vaccine-to-post-serum interval (28-57 days, mean 40). Coded pre and post sera were tested by radioimmunoassay for ug/ml of anti-PRP antibody.The geometric mean titer (GMT) for the entire group of children rose 48 fold from 0.126 (PRP, 0.158; PRP-D, 0.104) to 6.16 (PRP, 2.45 or 16 fold vs. PRP-D, 12.88 or 123 fold; p=.006, p=.001 for fold rise difference). A total of 34 children (16 PRP; 18 PRP-D) with pre titers <0.125 rose 80 fold from a GMT of 0.045 (PRP, 0.046; PRP-D, 0.044) to 3.60 (PRP, 1.35 or 30 fold vs. PRP-D, 8.51 or 195 fold; p=.019, p=.025 for rise). Eighty-eight, 68 and 28% of PRP children and 100, 97 and 60% of PRP-D children achieved titers of≥0.1, ≥1.0 and≥5.0 respectively. Only 5% or 16% of the total group ended up with possibly inadequate titers <0.1 or<:1.0 respectively.Thus both vaccines were immunogenic in most sickle cell children and are likely to protect. However, PRP-D appears to be more immunogenic than PRP in our population at 1-2 mos after vaccination.

PERSISTENCE OF ANTIBODY (AB) TO HAEMOPHILUS INFLUENZAE TYPE B (HIB) AND RESPONSE TO PRP AND PRP-D BOOS-TER IMMUNIZATION IN CHILDREN INITIALLY IMMUNIZED WITH EITHER VACCINE AT 15 TO 24 MONTHS

Children initially imnunized with PRP or PRP-D conjugate vaccines between 15 and 24 months of age were assessed 1 year later for persistence of AB and response to revaccination with PRP, PRP-D, or normal saline (N=111). Pre and post-vaccination sera were obtained and anti-PRP antibodies were assayed by RIA. Adverse reactions were minor and noted in <5% of vaccinees. AB levels a year after initial immunization were significantly higher in subjects immunized with PRP-D(GM 1.12 ug/ml) than with PRP (0.22 ug/ml)(p<.0001). All groups demonstrated an increase in anti-PRP levels after revaccination, although this response was significantly greater in subjects initially immunized with PRP-D, regardless of booster vaccine given. Initial vaccine:Children immunized with PRP or PRP-D between 15 to 24 months of age respond dramatically to reimmnunization one year later, although children previously immunized with PRP-D show the greatest responses even with conventional PRP antigen.

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 ≥ 1.0 μg/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 < 0.05). The lower levels of antibody production than previously reported may necessitate a reevaluation of current recommendations.

RESPONSE OF IgG SUBCLASS DEFICIENT PATIENTS TO H. INFLUENZA TYPE b POLYRIBOSE PHOSPHATE (PRP) DIPHTHERIA TOXOID CONJUGATE (PRP-D) VACCINE

The efficacy of PRP-D vaccine in young infants has been documented in previous studies. We now report the response of patients with IgG subclass deficiency (GSD) to a single immunization with PRP-D. Patients with GSD ranging in age from 6 to 10 years were given a single i.m. dose of 20 μg PRP-D. Total serum anti-PRP antibody levels were determined using a modified Farr assay and radiolabeled PRP. Four patients with GSD and no major abnormalities in B- and T-cell subsets or in vitro mitogen stimulation had a mean preimmunization anti-PRP level of 1.61 μg/ml which rose to 22.6 μg/ml 3-4 weeks after immunization. The mean increase in anti-PRP for 3 patients with IgG2 deficiency was 18.8 μg/ml. Two patients with IgA and IgG2 deficiency responded with post-immunization anti-PRP levels of 10.8 and 40 μg/ml. Both of these patients failed to respond to immunization with a polyvalent pneumococcal polysaccharide (PS) vaccine. One patient with isolated IgG3 deficiency responded normally to diphtheria and tetanus toxoid, to 3 of 4 pneumococcal serotypes tested, and had a rise of anti-PRP antibody from 0.6 to 28.4 μg/ml. A fifth patient with common variable immunodeficiency had no response to immunization with any of the above vaccines. These data suggest that protein conjugate vaccines may lead to effective immunization of patients with defective PS antigen processing.

ANTIBODY RESPONSE TO HEMOPHILUS INFLUENZAE, TYPE B (HITS) PRP-D CONJUGATE VACCINE IN IMMUNOCOMPROMISED (IC) PATIENTS <2 YEARS OF AGE

IC children <2 yrs represent a group at increased risk of invasive HITB infection. PRP-D conjugate vaccine (Connaught) was administered IM to 9 IC children aged 2-23 mo to assess their antibody response. Three had solid tumors (1 hepatoblastoma, 1 Wilms, 1 neuroblastoma), 3 had sickle cell disease, 1 had AML, 1 had ALL and 1 was on immunosuppressive therapy post hepatic transplant. All cancer patients were in remission. There were no serious side effects following vaccine administration, and no children have had documented HITB infection to date. Pre and 1 mo post vaccine HITB antibody levels were measured by RIA; mean pre vaccine level was 0.025 μg/ml (range <0.012-0.12), and mean post vaccine level was O.460 μg/ml (range <0.012-1.89). Only 2/9. children achieved a protective titer ( >1 μg/ml). Of the non-responders, 4/7 were >18 mo. Three children, 16-21 mo, received a 2nd vaccine dose 1 mo after the first, and 1 responded. These data provide preliminary information regarding the response of IC children <2 yrs to PRP-D conjugate vaccine and indicate that IC children 18-23 mo do not reliably respond to a single dose of vaccine.