WASHINGTON — An updated pneumococcal conjugate vaccine containing 13 different bacterial strains appears to be safe and immunogenic, based on pilot data from four European studies including several hundred infants and toddlers.
The data were presented in a poster session at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and the annual meeting of the Infectious Diseases Society of America (IDSA).
“Globally, the pneumococcus has been estimated to account for around 1 million deaths annually in children less than 5 years old,” stated Dr. Dorothee Kieninger of Johannes Gutenberg University in Mainz, Germany, and colleagues.
Data from the Centers for Disease Control and Prevention in Atlanta have shown a significant decrease in pneumococcal disease in U.S. children thanks to the 7-valent pneumococcal conjugate vaccine (PCV7). But outbreaks of disease in recent years have been linked to bacterial strains not included in this vaccine, particularly serotype 19A, according to the CDC.
The studies presented at the meeting showed that the new vaccine appeared to generate an immune response with few adverse effects, but it must earn approval from the Food and Drug Administration before it can be licensed and distributed.
In Dr. Kieninger's study, 604 healthy 2-month-old infants in Germany were randomized to receive PCV7 (303 infants) or the new vaccine PCV13 (301 infants). The children received the pneumococcal vaccines in addition to a combined diphtheria, tetanus, and acellular pertussis (DTaP) vaccine, inactivated polio vaccine (IPV), Haemophilus influenzae type b polysaccharide PRP (Hib), and hepatitis B surface antigen (HBsAg) (GlaxoSmithKline's Infanrix hexa). They received the vaccinations at 2, 3, and 4 months, and again at 11–12 months. Blood samples were taken after the infant series at 5 months, and again after the toddler vaccination at 12–13 months.
The researchers compared adverse events and assessed immune responses to the seven serotypes in PCV7 (4, 6B, 9V, 14, 18C, 19F, and 23F) and the six additional strains in PCV13 (1, 3, 5, 6A, 7F, and 19A).
Overall, antibody responses to the PCV7 serotypes were similar in both groups. But for the six additional serotypes in PCV13, the functional antibodies were 10–100 times higher in the PCV13 group, compared with the PCV7 group.
The positive antibody response of 19A is of particular interest, given the increased incidence of pneumococcal disease caused by this serotype, Dr. Christine Juergens of Wyeth Research in Muenster, Germany, said in an interview.
The primary measure of immunogenicity in this study and the other PCV13 studies presented at the meeting was the proportion of children who achieved an antipolysaccharide IgG binding concentration of at least 0.35 mcg/mL. For 19A, this percentage was 99% in the PCV13 group.
The lack of interference from concomitant vaccines in the safety and effectiveness of PCV13 also is important, said Dr. Juergens, a coinvestigator for the study.
No clinically meaningful differences in safety or tolerability were observed between the two groups, the researchers said, and no severe adverse events were reported in either group in response to the infant dose. One incidence of febrile convulsion occurred in one toddler in the PCV7 group.
But there were some significant differences in local reactions between the PCV13 and PCV7 groups. Patients who received PCV13 compared with PCV7 reported significantly more induration (28% vs. 21%) but significantly less erythema (28% vs. 36%) after the first dose, and significantly less induration (27% vs. 35%) and erythema (34% vs. 47%) after the second dose. In addition, there was a significantly greater incidence of mild fever after the third dose in the PCV13 group, compared with the PCV7 group (46% vs. 37%) but there was a significantly lower incidence of sleepiness after the second dose in the PCV13 group, compared with the PCV7 group (54% vs. 67%).
Data from another study of a three-dose infant vaccination series showed similar safety and immunogenicity results for PCV7 and PCV13 when each vaccine was given along with a DTaP, IPV, and Hib vaccine (Sanofi Pasteur's Pentavac). This study was conducted in France by Dr. Emmanuel Grimprel of the Armand Trousseau Hospital in Paris, and colleagues.
Overall, the immune responses to the concomitant antigens for a three-dose infant series were similar between a group of 266 healthy 2-month-olds who were randomized to receive PCV13 and 263 who received PCV7. The infants were vaccinated at 2, 3, and 4 months of age, and blood samples were taken at 5 months to measure immune response.
After dose 3 of the infant series, the pneumococcal immune response rate in the PCV13 group was at least 72% for all serotypes and 98% for 19A. Antibody response rates to the concomitant vaccine ranged from 59% to 100% in the PCV13 group and 63% to 100% in the PCV7 group.