Safety and Efficacy Trials
Rennels and colleagues found PCV7 to be both safe and effective in a large clinical trial performed in the United States.2 In this study, PCV7 was administered to children at 2, 4, 6, and 12 to 15 months of age. The vaccine was immunogenic and was demonstrated to induce a significant amnestic response to every serotype included in its formulation, especially after the fourth, or booster, dose.
The vaccine's efficacy was also evaluated in a recently published clinical trial by Black and coworkers. In this double-blind trial, PCV7 was given to infants at 2, 4, 6, and 12-15 months of age. The study included 37,868 children, of which 18,927 and 18,941 received one or more doses of pneumococcal conjugate and meningococcal conjugate vaccine, respectively. Both groups received their routine immunizations according to the standard American Academy of Pediatrics (AAP) schedule for that time period.
The primary endpoint of this study was development of pneumococcal disease due to vaccine serotypes. All cases of pneumococcal disease that occurred more than 14 days after the third dose were included in the protocol analysis. Intention-to-treat analysis included all cases of invasive pneumococcal disease due to vaccine serotypes in children who received at least one vaccine dose. The secondary efficacy endpoint was development of invasive pneumococcal disease regardless of serotype. Other endpoints included the number of episodes of otitis media, differences between treatment groups in time to diagnosis of otitis media, placement of ventilator tympanostomy tubes, and number of cases of spontaneously draining ruptured tympanic membranes with a culture of vaccine serotypes.
Of all the children included in this study, invasive disease caused by strains included in the vaccine occurred in 40 children, 29 of whom were in the control group. In the intent-to-treat analysis, 52 children, including 49 from the control group, developed invasive disease. The vaccine's effectiveness in preventing disease caused by the serotypes included in the formulation was calculated to be 97.4% and 93.9% for the fully vaccinated and intent-to-treat groups, respectively. The effectiveness in preventing invasive disease caused by all serotypes was 89.1%. In addition, the vaccine provided a 7% reduction in otitis media. The authors concluded that PCV7 is effective in preventing invasive disease caused by Streptococcus pneumoniae.
Immunogenicity and safety were evaluated in a subset of patients enrolled in the study. In addition, the effect of concurrent vaccines on immunogenicity was also investigated. The patients received either PCV7 or the combination product containing conjugate Haemophilus b, diphtheria, tetanus toxoid, and whole cell pertussis (DTwP-HbOC). Both groups received the oral polio vaccine (OPV) concurrently. Half of the subjects also received hepatitis B (HepB) vaccine at each visit in the same thigh as the DTwP-HbOC and half received HepB at least two weeks before or after the investigational vaccine. At 12-15 months, patients received the fourth dose of the study vaccine with diphtheria toxoid, tetanus toxoid, and acellular pertussis (DTaP) and conjugate H. influenzae type b (HbOC), study vaccine alone, or DTaP and HbOC alone.
Of the 302 subjects recruited for this study, 272 completed the three dose primary series, and 211 received the 12-15 month booster doses. Immunologic responses to all seven pneumococcal serotypes occurred. There was a drop in antibody concentration for all serotypes before the booster dose. One month following the booster, all geometric means of antibody concentrations (GMCs) were above 1 ug/mL. There were no significant differences in GMCs of pneumococcal serotypes between subjects who received HepB vaccination concurrently or 2 weeks apart from the pneumococcal vaccine. Antibody titers to HepB and poliovirus types 1, 2, and 3 were present in 92.6%, 95.2%, 100% of patients, respectively. Although GMCs were higher when PCV7 was administered alone as opposed to administration with DTaP and HbOC, differences in the proportion of subjects with antibody concentrations above 1 ug/mL for all seven serotypes were not greater than 10%. The authors concluded that PCV7 is immunogenic and the differences observed in GMCs when PCV7 was administered concurrently with DTaP and HbOC were not clinically significant.
In clinical trials, PCV7 has been administered simultaneously with DTP-HbOC, DTaP, HbOC, HepB, OPV, inactivated polio vaccine (IPV), measles mumps rubella (MMR) and varicella vaccines. In infants, enhanced antibody response to HbOC was observed. Some suppression of response to HbOC was observed at the fourth dose; however, 97% of children achieved titers >1 ug/ml. Responses to pertussis antigens were inconsistent, but the clinical significance of this is unknown. Three months after two doses of IPV were administered concomitantly with PCV7, response to poliovirus types 2 and 3 were consistent with controls; however, titers for poliovirus type 1 were lower. Immunogenicity data for MMR and varicella vaccines administered with PCV7 are not yet available.
PCV7 is contraindicated in patients with known hypersensitivity to diphtheria toxoid or latex. It should not be given to individuals with thrombocytopenia or coagulation disorders that would contraindicate intramuscular injection.1
In clinical trials, fever >38.0°C, irritability, drowsiness, restless sleep, decreased appetite, vomiting, diarrhea, and rash or hives were reported more frequently in the PCV7 group within two to three days of vaccination than in controls. Within 48 to 72 hours of vaccination, patients may also experience edema, pain or tenderness, redness, inflammation or skin discoloration, mass, or local hypersensitivity at or around the injection site.[1,2,3]
PCV7 should be given intramuscularly (IM) using a dose of 0.5 ml. Preferred sites are the anterolateral aspect of the thigh in infants or the deltoid muscle of the upper arm in toddlers and young children. For infants, the recommended immunization series consists of three doses at two month intervals followed by a fourth dose at 12-15 months of age. For previously unvaccinated older infants and children who are beyond the age of the routine infant schedule, the following schedule should be used.8
Two doses of PCV7 are recommended for children 24 to 59 months old at high risk of invasive pneumococcal infection who have not been immunized previously with PCV7. These children also should receive 23PS to expand serotype coverage. High-risk children should be given vaccines at the earliest possible opportunity (Tables 2 and 3).
Indications for use of PCV7 and 23PS in children 24 months or older at moderate or lower risk remain under investigation. All children 24 to 59 months old, even those not in high or moderate risk groups, may benefit from the administration of a single dose of PCV7 or 23PS. The 23PS is an acceptable alternative, although an enhanced immune response and probable reduction of nasopharyngeal carriage favor use of PCV7.
Pediatr Pharm. 2000;6(8) © 2000 Children's Medical Center, University of Virginia
Cite this: Pneumococcal Conjugate Vaccine - Medscape - Aug 01, 2000.