PCV13 Is Promising Against Worrisome Serotypes

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.

In this study, as in other studies, the incidence of adverse events including injection site tenderness, erythema, and induration were not significantly different between the two groups.

The results from the French study were mirrored in a similar study conducted by Dr. Chaamala Klinger of the University of Oxford (England), and colleagues. This study included data from 135 infants aged 6–14 weeks who were randomized to receive PCV13 and 132 infants who received PCV7. Infants in both groups received the meningococcal serotype C vaccine at 2 and 4 months of age, and the pneumococcal conjugate vaccine, plus a DTaP, IPV, and Hib vaccine at age 2, 3, and 4 months.

Overall, 79%–96% of the children who received PCV13 met the criteria for protection against the six serotypes not included in PCV7, and 95% met the criteria for protection against 19A. “PCV13 was immunogenic and well tolerated when given as part of the UK infant vaccine course,” the researchers wrote.

Local reactions including tenderness, induration, and erythema were similar between the two groups, as were systemic reactions.

A study of the safety and immunogenicity of PCV13 when it was produced on a manufacturing scale supported the results from the three pilot studies.

In this study, conducted by Dr. Janusz Gadzinowski of the Poznan (Poland) University of Medical Sciences, and colleagues, 134 healthy 2-month-olds were randomized to receive the PCV13 pilot vaccine and 135 received the PCV13 manufacturing scale vaccine.

The infants in each group received the PCV13 along with a DTaP, IPV, Hib vaccine, and a hepatitis B vaccine. The infants were vaccinated at 2, 3, and 4 months of age, and the researchers took blood samples at 5 months to test for immune response.

Overall, the proportions of responders who met the criteria for immunogenicity and geometric mean concentration were similar in both groups. For serotype 19A, both groups achieved identical response rates of 99%.

Adverse events were mostly mild or moderate and the investigators considered them unrelated to vaccine. Only one serious adverse event (a case of inconsolable crying) was considered vaccine related, they said. All four studies were supported by Wyeth, a manufacturer of PCV13.

S. pneumoniae Serotype 19A Tied To Necrotizing Pneumonia in Kids

Serotype 19A of Streptococcus pneumoniae is the culprit behind some complicated cases of necrotizing pneumonia in young children, based on findings from four cases that occurred between Sept. 7, 2007, and March 30, 2008, at a single hospital.

“Severe necrotizing pneumonia caused by this serotype had not previously been reported in children,” said Dr. Susan Wootton of the University of Texas, Houston, who presented the cases with her associates in a poster at the jointly held annual meeting of ICAAC and IDSA.

The 19A strain is one of several that are not included in the current pneumococcal conjugate vaccine, PCV7. Data from the Centers for Disease Control and Prevention that also were presented at the meeting showed an increase in invasive pneumococcal disease from nonvaccine serotypes in all age groups.

The patients ranged in age from 3 to 4 years (mean age, 3.4 years). Three were previously healthy and one had asthma. All four had been vaccinated with PCV7. S. pneumoniae was isolated from pleural fluid in three cases and from blood in three cases.

Chest radiographs revealed multilobar infiltrates in four children, empyema in three, and pneumatoceles in two. Three children were admitted to the intensive care unit and intubated 5–22 days. Three children had abscesses that required surgical drainage. The hospital stays ranged from 11 to 28 days.

Serotype 19A has not previously been reported as a cause of complicated pneumonia in children, but these cases suggest that it should now be considered in the differential diagnosis, Dr. Wootton and her associates noted. The results support the need for an expanded pneumococcal vaccine, they said.

Dr. Wootton had no financial conflicts to disclose.

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.

In this study, as in other studies, the incidence of adverse events including injection site tenderness, erythema, and induration were not significantly different between the two groups.

The results from the French study were mirrored in a similar study conducted by Dr. Chaamala Klinger of the University of Oxford (England), and colleagues. This study included data from 135 infants aged 6–14 weeks who were randomized to receive PCV13 and 132 infants who received PCV7. Infants in both groups received the meningococcal serotype C vaccine at 2 and 4 months of age, and the pneumococcal conjugate vaccine, plus a DTaP, IPV, and Hib vaccine at age 2, 3, and 4 months.

Overall, 79%–96% of the children who received PCV13 met the criteria for protection against the six serotypes not included in PCV7, and 95% met the criteria for protection against 19A. “PCV13 was immunogenic and well tolerated when given as part of the UK infant vaccine course,” the researchers wrote.

Local reactions including tenderness, induration, and erythema were similar between the two groups, as were systemic reactions.

A study of the safety and immunogenicity of PCV13 when it was produced on a manufacturing scale supported the results from the three pilot studies.

In this study, conducted by Dr. Janusz Gadzinowski of the Poznan (Poland) University of Medical Sciences, and colleagues, 134 healthy 2-month-olds were randomized to receive the PCV13 pilot vaccine and 135 received the PCV13 manufacturing scale vaccine.

The infants in each group received the PCV13 along with a DTaP, IPV, Hib vaccine, and a hepatitis B vaccine. The infants were vaccinated at 2, 3, and 4 months of age, and the researchers took blood samples at 5 months to test for immune response.

Overall, the proportions of responders who met the criteria for immunogenicity and geometric mean concentration were similar in both groups. For serotype 19A, both groups achieved identical response rates of 99%.

Adverse events were mostly mild or moderate and the investigators considered them unrelated to vaccine. Only one serious adverse event (a case of inconsolable crying) was considered vaccine related, they said. All four studies were supported by Wyeth, a manufacturer of PCV13.

S. pneumoniae Serotype 19A Tied To Necrotizing Pneumonia in Kids

Serotype 19A of Streptococcus pneumoniae is the culprit behind some complicated cases of necrotizing pneumonia in young children, based on findings from four cases that occurred between Sept. 7, 2007, and March 30, 2008, at a single hospital.

“Severe necrotizing pneumonia caused by this serotype had not previously been reported in children,” said Dr. Susan Wootton of the University of Texas, Houston, who presented the cases with her associates in a poster at the jointly held annual meeting of ICAAC and IDSA.

The 19A strain is one of several that are not included in the current pneumococcal conjugate vaccine, PCV7. Data from the Centers for Disease Control and Prevention that also were presented at the meeting showed an increase in invasive pneumococcal disease from nonvaccine serotypes in all age groups.

The patients ranged in age from 3 to 4 years (mean age, 3.4 years). Three were previously healthy and one had asthma. All four had been vaccinated with PCV7. S. pneumoniae was isolated from pleural fluid in three cases and from blood in three cases.

Chest radiographs revealed multilobar infiltrates in four children, empyema in three, and pneumatoceles in two. Three children were admitted to the intensive care unit and intubated 5–22 days. Three children had abscesses that required surgical drainage. The hospital stays ranged from 11 to 28 days.

Serotype 19A has not previously been reported as a cause of complicated pneumonia in children, but these cases suggest that it should now be considered in the differential diagnosis, Dr. Wootton and her associates noted. The results support the need for an expanded pneumococcal vaccine, they said.

Dr. Wootton had no financial conflicts to disclose.

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.

In this study, as in other studies, the incidence of adverse events including injection site tenderness, erythema, and induration were not significantly different between the two groups.

The results from the French study were mirrored in a similar study conducted by Dr. Chaamala Klinger of the University of Oxford (England), and colleagues. This study included data from 135 infants aged 6–14 weeks who were randomized to receive PCV13 and 132 infants who received PCV7. Infants in both groups received the meningococcal serotype C vaccine at 2 and 4 months of age, and the pneumococcal conjugate vaccine, plus a DTaP, IPV, and Hib vaccine at age 2, 3, and 4 months.

Overall, 79%–96% of the children who received PCV13 met the criteria for protection against the six serotypes not included in PCV7, and 95% met the criteria for protection against 19A. “PCV13 was immunogenic and well tolerated when given as part of the UK infant vaccine course,” the researchers wrote.

Local reactions including tenderness, induration, and erythema were similar between the two groups, as were systemic reactions.

A study of the safety and immunogenicity of PCV13 when it was produced on a manufacturing scale supported the results from the three pilot studies.

In this study, conducted by Dr. Janusz Gadzinowski of the Poznan (Poland) University of Medical Sciences, and colleagues, 134 healthy 2-month-olds were randomized to receive the PCV13 pilot vaccine and 135 received the PCV13 manufacturing scale vaccine.

The infants in each group received the PCV13 along with a DTaP, IPV, Hib vaccine, and a hepatitis B vaccine. The infants were vaccinated at 2, 3, and 4 months of age, and the researchers took blood samples at 5 months to test for immune response.

Overall, the proportions of responders who met the criteria for immunogenicity and geometric mean concentration were similar in both groups. For serotype 19A, both groups achieved identical response rates of 99%.

Adverse events were mostly mild or moderate and the investigators considered them unrelated to vaccine. Only one serious adverse event (a case of inconsolable crying) was considered vaccine related, they said. All four studies were supported by Wyeth, a manufacturer of PCV13.

S. pneumoniae Serotype 19A Tied To Necrotizing Pneumonia in Kids

Serotype 19A of Streptococcus pneumoniae is the culprit behind some complicated cases of necrotizing pneumonia in young children, based on findings from four cases that occurred between Sept. 7, 2007, and March 30, 2008, at a single hospital.

“Severe necrotizing pneumonia caused by this serotype had not previously been reported in children,” said Dr. Susan Wootton of the University of Texas, Houston, who presented the cases with her associates in a poster at the jointly held annual meeting of ICAAC and IDSA.

The 19A strain is one of several that are not included in the current pneumococcal conjugate vaccine, PCV7. Data from the Centers for Disease Control and Prevention that also were presented at the meeting showed an increase in invasive pneumococcal disease from nonvaccine serotypes in all age groups.

The patients ranged in age from 3 to 4 years (mean age, 3.4 years). Three were previously healthy and one had asthma. All four had been vaccinated with PCV7. S. pneumoniae was isolated from pleural fluid in three cases and from blood in three cases.

Chest radiographs revealed multilobar infiltrates in four children, empyema in three, and pneumatoceles in two. Three children were admitted to the intensive care unit and intubated 5–22 days. Three children had abscesses that required surgical drainage. The hospital stays ranged from 11 to 28 days.

Serotype 19A has not previously been reported as a cause of complicated pneumonia in children, but these cases suggest that it should now be considered in the differential diagnosis, Dr. Wootton and her associates noted. The results support the need for an expanded pneumococcal vaccine, they said.

Dr. Wootton had no financial conflicts to disclose.