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Acthib

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ActHIB

CLINICAL PHARMACOLOGY

H influenzae type b was the leading cause of invasive bacterial disease among children in the United States prior to licensing of Haemophilus b conjugate vaccines.

The response to ActHIB vaccine is typical of a T-dependent immune response to antigen. The prominent isotype of anti-capsular PRP antibody induced by ActHIB vaccine is IgG.3 A booster response for IgG has been demonstrated in children 12 months of age or older who previously received two or three doses of ActHIB vaccine. Bactericidal activity against H influenzae type b was demonstrated in serum after immunization and correlated with the anti-PRP antibody response induced by ActHIB vaccine.4

Antibody to H influenzae capsular polysaccharide (anti-PRP) titers of > 1.0 mcg/mL following vaccination with unconjugated PRP vaccine correlated with long-term protection against invasive H influenzae type b disease in children older than 24 months of age.5 Although the relevance of this threshold to clinical protection after immunization with conjugate vaccines is not known, particularly in light of the induced, immunologic memory, this level continues to be considered as indicative of long-term protection.6 In clinical studies, ActHIB vaccine induced, on average, anti-PRP levels ≥ 1.0 mcg/mL in 90% of infants after the primary series (2, 4, and 6 months) and in more than 98% of infants following a booster dose given at 15 to 19 months of age.4

Two clinical trials supported by the National Institutes of Health (NIH) have compared the anti- PRP antibody responses to three Haemophilus b conjugate vaccines in racially mixed populations of children. These studies were done in Tennessee7 (TABLE 1) and in Minnesota, Missouri, and Texas (8) (TABLE 2) in infants immunized with ActHIB vaccine and other Haemophilus b conjugate vaccines at 2, 4, and 6 months of age. All Haemophilus b conjugate vaccines were administered concomitantly with Poliovirus Vaccine Live Oral and whole cell DTP vaccines at separate sites. Neither Poliovirus Vaccine Live Oral nor whole cell DTP vaccines are licensed or distributed in the US.

TABLE 1: Anti-PRP Antibody Responses Following a Two or Three Dose Series of a Haemophilus b Vaccine at 2, 4, and 6 Months of Age - Tennessee7

VACCINE Na GEOMETRIC MEAN CONCENTRATION (GMC) (mcg/mL) Post Third Immunization % ≥ 1.0 mcg/mL
PreImmunization at 2 months Post Second Immunization at 6 months Post Third Immunization at 7 months
PRP-Tb (ActHIB vaccine) 65 0.10 0.30 3.64 83%
PRP-OMPc (PedvaxHIB®) 64 0.11 0.84 N/A 50%d
HbOCe (HibTITER®) 61 0.07 0.13 3.08 75%
a N = Number of Children
b Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate)
c Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate)
d Seroconversion after the recommended 2-dose primary immunization series is shown
e Haemophilus b Conjugate Vaccine (Diphtheria CRMW7 Protein Conjugate)
N/A Not applicable in this comparison trial although third dose data have been published7

TABLE 2: Anti-PRP Antibody Responses Following a Two or Three Dose Series of a Haemophilus b Vaccine at 2, 4, and 6 Months of Age - Minnesota, Missouri, and Texas8

VACCINE Na GEOMETRIC MEAN CONCENTRATION (GMC) (mcg/mL) Post Thirdb Immunization % ≥ 1.0 mcg/mL
Pre Immunization at 2 months Post Second Immunization At 6 months Post Thirdb Immunization At 7 months
PRP-Tc (ActHIB vaccine) 142 0.25 1.25 6.37 97%
PRP-OMPd (PedvaxHIB) 149 0.18 4.00 N/A 85%e
HbOCf (HibTITER) 167 0.17 0.45 6.31 90%
a N = Number of Children
b Sera were obtained after the third dose from 86 and 110 infants, in PRP-T and HbOC vaccine groups, respectively
c Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate)
d Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate)
e Seroconversion after the recommended 2-dose primary immunization series is shown
f Haemophilus b Conjugate Vaccine (Diphtheria CRM197 Protein Conjugate)
N/A Not applicable in this comparison trial although third dose data have been published8

Native American populations have had high rates of H influenzae type b disease and have been observed to have low immune responses to Haemophilus b conjugate vaccines. In a clinical study enrolling Alaskan Native Americans, following the administration of a three dose series of ActHIB at 6 weeks, 4 months, and 6 months of age, 75% of subjects achieved an anti-PRP antibody titer of ≥ 1.0 mcg/mL at 7 months of age (1 month after the last vaccination).9

In four separate studies, children 12 to 24 months of age who had not previously received Haemophilus b conjugate vaccination were immunized with a single dose of ActHIB vaccine (TABLE 3). GMC anti-PRP antibody responses were 5.12 mcg/mL (90% responding with ≥ 1.0 mcg/mL) for children 12 to 15 months of age and 4.4 mcg/mL (82% responding with ≥ 1.0 mcg/mL) for children 17 to 24 months of age.10

TABLE 3: Anti-PRP Antibody Responses in 12- to 24-month-old Children Immunized with a Single Dose of ActHIB10

AGE GROUP Na GEOMETRIC MEAN CONCENTRATION (GMC) (mcg/mL) % SUBJECTS WITH ≥ 1.0 mcg/mL
Pre Immunization Post Immunizationb Pre Immunization Post Immunizationb
12 to 15 months 256 0.06 5.12 1.6 90.2
17 to 24 months 81 0.10 4.40 3.7 81.5
a N = Number of Children
b Post immunization responses measured at approximately 1 month after vaccination

ActHIB vaccine has been found to be immunogenic in children with sickle cell anemia, a condition which may cause increased susceptibility to Haemophilus b disease. Following two doses of ActHIB vaccine given at two-month intervals, 89% of these children (mean age 11 months) had anti-PRP antibody titers of ≥ 1.0 mcg/mL. This is comparable to anti-PRP antibody levels demonstrated in normal children of similar age following two doses of ActHIB vaccine.11

TriHIBit Vaccine (ActHIB vaccine combined with Tripedia vaccine by reconstitution)

Randomized comparative clinical trials demonstrated that the anti-PRP response achieved in 15- to 20-month-old children 1 month after one dose of TriHIBit vaccine (ActHIB vaccine reconstituted with Tripedia vaccine) was similar to that achieved when the ActHIB and Tripedia vaccines were given concomitantly at different sites with separate needles and syringes (TABLE 4).10 All children had received three doses of a Haemophilus b conjugate vaccine (HibTITER or ActHIB vaccine) and three doses of a whole-cell DTP vaccine prior to entry into this clinical trial.

TABLE 4: Anti-PRP Responses in 15- to 20-month-old Children Following Immunization with TriHIBit Vaccine Compared to ActHIB Vaccine and Tripedia Vaccine Given Concomitantly at Separate Sites10

  IMMUNOGENICITY
Pre-Dose Post-Dose (1 month post-vaccination)
TriHIBit vaccine Separate Injectionsa TriHIBit vaccine Separate Injectionsa
Nb 88 94 93 98
Anti-PRP (mcg/mL) 0.89 1.15 90.30 80.90
% > 1 mcg/mL 45.50 53.20 100.00 100.00
a ActHIB and Tripedia administered concomitantly at separate sites
b N= Number of Children

For data on the antibody responses to diphtheria, tetanus and pertussis (PT and FHA) antigens in this study, refer to the Tripedia vaccine product insert.

REFERENCES

3 Holmes SJ, et al. Immunogenicity of four Haemophilus influenzae type b conjugate vaccines in 17- to 19-month-old children. J Pediatr 118:364-371, 1991.

4 Data on file, Sanofi Pasteur SA.

5 Peltola H, et al. Prevention of Haemophilus influenzae type b bacteremic infections with the capsular polysaccharide vaccine. N Engl J Med 310:1561-1566, 1984.

6 Recommendations of the Immunization Practices Advisory Committee (ACIP). Haemophilus b conjugate vaccines for prevention of Haemophilus influenzae type b disease among infants and children two months of age and older. MMWR 40:No. RR-1, 1991.

7 Decker MD, et al. Comparative trial in infants of four conjugate Haemophilus influenza type b vaccines. J Pediatr 120:184-189, 1992.

8 Granoff DM, et al. Differences in the immunogenicityof three Haemophilus influenzae type b conjugate vaccines in infants. J Pediatr 121:187-194, 1992.

9 Bulkow LR, et al. Comparative immunogenicity of four Haemophilus influenzae type b conjugate vaccines in Alaska Native infants. Pediatr Infect Dis J 12:484-92, 1993.

10 Data on file, Sanofi Pasteur Inc.

11 Kaplan SL, et al. Immunogenicity of Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine in children with sickle hemoglobinopathy or malignancies, and after systemic Haemophilus influenzae type b infection. J Pediatr 120:367-370, 1992.

Last reviewed on RxList: 8/21/2014
This monograph has been modified to include the generic and brand name in many instances.

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