Safety and immunogenicity of pneumococcal conjugate vaccine in combination with diphtheria, tetanus toxoid, pertussis and Haemophilus influenzae type b conjugate vaccine

Stephen K Obaro, Godwin C. Enwere, Maria Deloria, Shabbar Jaffar, David Goldblatt, Kate Brainsby, Hans Hallander, Pamela McInnes, Brian M. Greenwood, Keith P.W.J. McAdam

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background. Pneumococcal polysaccharide/ protein conjugate vaccines (PnCV) are immunogenic and effective in infancy. However, an addition to the nine currently recommended vaccine injections during the first year of life of African children may be a deterrent to participation in a PnCV program. Thus we have evaluated the safety and immunogenicity of a 9-valent PnCV (Wyeth Lederle Pediatrics and Vaccines) mixed with diphtheria, tetanus toxoid, cell pertussis and Haemophilus influenzae type b (TETRAMUNE). Methods. Healthy Gambian infants were randomized at the age of 2 months to receive three doses 1 month apart of either (1) placebo reconstituted in TETRAMUNE in the right thigh (control) or (2) PnCV in the left thigh and TETRAMUNE in the right thigh (separate) or (3) PnCV reconstituted in TETRAMUNE as a single injection in the right thigh (combined). The vaccines were given together with routine Expanded Program on Immunization vaccines. Adverse reactions were recorded after vaccination, and antibody concentrations were measured by enzyme-linked immunosorbent assays. Results. Local induration and tenderness were observed more commonly at the site of injection of TETRAMUNE than at the site of injection with PnCV after each dose of vaccination. Swelling at the site of injection was encountered more frequently at the site of administration of TETRAMUNE than at the site of administration PnCV (P < 0.00001 for Doses 1 and 2 and P < 0.0009 for Dose 3). Swelling at the site of administration of TETRAMUNE mixed with PnCV was comparable with that observed for TETRAMUNE alone. Although most mothers reported that the babies "felt hot" 24 h after each injection, febrile reactions (temperature, ≥38°C) were infrequent and resolved with antipyretics. Geometric mean titer for anti-polyribosylribitol phosphate antibody was 11.6 μg/ml [95% confidence limits (95% CI), 9.2, 14.6] in the control group and comparable with 13.3 μg/ml (95% CI 11.0, 16.0) in the combined group and significantly higher at 17.9 μg/ml (95% CI 14.7, 21.9; P = 0.01) in the separate group. Geometric mean concentrations of serotype-specific pneumococcal antibodies were higher in the combined group than the separate group for all nine serotypes. Antibody responses to diphtheria and pertussis antigens were similar in all groups. Anti-tetanus toxoid antibody concentrations were lowest in the combined group (6.66 IU/ml, 95% CI 5.77, 7.68 in the control group; 5.15 IU/ml, 95% CI 4.39, 6.03 in the combined group; P = 0.02). However, all vaccinees achieved protective antibody values. Conclusion. The combination of TETRAMUNE and PnCV is safe and immunogenic.

Original languageEnglish (US)
Pages (from-to)940-946
Number of pages7
JournalPediatric Infectious Disease Journal
Volume21
Issue number10
DOIs
StatePublished - Oct 1 2002

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Diphtheria Toxoid
Haemophilus influenzae type b
Conjugate Vaccines
Pneumococcal Vaccines
Tetanus Toxoid
Whooping Cough
Safety
Thigh
Injections
Proteins
Vaccines
Antibodies
Vaccination
Immunization Programs
Antipyretics
Control Groups
Diphtheria
Antibody Formation
Polysaccharides
Fever

Keywords

  • African infant
  • Immunogenicity
  • Pneumococcal conjugate vaccine
  • Safety
  • TETRAMUNE

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Microbiology (medical)
  • Infectious Diseases

Cite this

Safety and immunogenicity of pneumococcal conjugate vaccine in combination with diphtheria, tetanus toxoid, pertussis and Haemophilus influenzae type b conjugate vaccine. / Obaro, Stephen K; Enwere, Godwin C.; Deloria, Maria; Jaffar, Shabbar; Goldblatt, David; Brainsby, Kate; Hallander, Hans; McInnes, Pamela; Greenwood, Brian M.; McAdam, Keith P.W.J.

In: Pediatric Infectious Disease Journal, Vol. 21, No. 10, 01.10.2002, p. 940-946.

Research output: Contribution to journalArticle

Obaro, Stephen K ; Enwere, Godwin C. ; Deloria, Maria ; Jaffar, Shabbar ; Goldblatt, David ; Brainsby, Kate ; Hallander, Hans ; McInnes, Pamela ; Greenwood, Brian M. ; McAdam, Keith P.W.J. / Safety and immunogenicity of pneumococcal conjugate vaccine in combination with diphtheria, tetanus toxoid, pertussis and Haemophilus influenzae type b conjugate vaccine. In: Pediatric Infectious Disease Journal. 2002 ; Vol. 21, No. 10. pp. 940-946.
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abstract = "Background. Pneumococcal polysaccharide/ protein conjugate vaccines (PnCV) are immunogenic and effective in infancy. However, an addition to the nine currently recommended vaccine injections during the first year of life of African children may be a deterrent to participation in a PnCV program. Thus we have evaluated the safety and immunogenicity of a 9-valent PnCV (Wyeth Lederle Pediatrics and Vaccines) mixed with diphtheria, tetanus toxoid, cell pertussis and Haemophilus influenzae type b (TETRAMUNE). Methods. Healthy Gambian infants were randomized at the age of 2 months to receive three doses 1 month apart of either (1) placebo reconstituted in TETRAMUNE in the right thigh (control) or (2) PnCV in the left thigh and TETRAMUNE in the right thigh (separate) or (3) PnCV reconstituted in TETRAMUNE as a single injection in the right thigh (combined). The vaccines were given together with routine Expanded Program on Immunization vaccines. Adverse reactions were recorded after vaccination, and antibody concentrations were measured by enzyme-linked immunosorbent assays. Results. Local induration and tenderness were observed more commonly at the site of injection of TETRAMUNE than at the site of injection with PnCV after each dose of vaccination. Swelling at the site of injection was encountered more frequently at the site of administration of TETRAMUNE than at the site of administration PnCV (P < 0.00001 for Doses 1 and 2 and P < 0.0009 for Dose 3). Swelling at the site of administration of TETRAMUNE mixed with PnCV was comparable with that observed for TETRAMUNE alone. Although most mothers reported that the babies {"}felt hot{"} 24 h after each injection, febrile reactions (temperature, ≥38°C) were infrequent and resolved with antipyretics. Geometric mean titer for anti-polyribosylribitol phosphate antibody was 11.6 μg/ml [95{\%} confidence limits (95{\%} CI), 9.2, 14.6] in the control group and comparable with 13.3 μg/ml (95{\%} CI 11.0, 16.0) in the combined group and significantly higher at 17.9 μg/ml (95{\%} CI 14.7, 21.9; P = 0.01) in the separate group. Geometric mean concentrations of serotype-specific pneumococcal antibodies were higher in the combined group than the separate group for all nine serotypes. Antibody responses to diphtheria and pertussis antigens were similar in all groups. Anti-tetanus toxoid antibody concentrations were lowest in the combined group (6.66 IU/ml, 95{\%} CI 5.77, 7.68 in the control group; 5.15 IU/ml, 95{\%} CI 4.39, 6.03 in the combined group; P = 0.02). However, all vaccinees achieved protective antibody values. Conclusion. The combination of TETRAMUNE and PnCV is safe and immunogenic.",
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TY - JOUR

T1 - Safety and immunogenicity of pneumococcal conjugate vaccine in combination with diphtheria, tetanus toxoid, pertussis and Haemophilus influenzae type b conjugate vaccine

AU - Obaro, Stephen K

AU - Enwere, Godwin C.

AU - Deloria, Maria

AU - Jaffar, Shabbar

AU - Goldblatt, David

AU - Brainsby, Kate

AU - Hallander, Hans

AU - McInnes, Pamela

AU - Greenwood, Brian M.

AU - McAdam, Keith P.W.J.

PY - 2002/10/1

Y1 - 2002/10/1

N2 - Background. Pneumococcal polysaccharide/ protein conjugate vaccines (PnCV) are immunogenic and effective in infancy. However, an addition to the nine currently recommended vaccine injections during the first year of life of African children may be a deterrent to participation in a PnCV program. Thus we have evaluated the safety and immunogenicity of a 9-valent PnCV (Wyeth Lederle Pediatrics and Vaccines) mixed with diphtheria, tetanus toxoid, cell pertussis and Haemophilus influenzae type b (TETRAMUNE). Methods. Healthy Gambian infants were randomized at the age of 2 months to receive three doses 1 month apart of either (1) placebo reconstituted in TETRAMUNE in the right thigh (control) or (2) PnCV in the left thigh and TETRAMUNE in the right thigh (separate) or (3) PnCV reconstituted in TETRAMUNE as a single injection in the right thigh (combined). The vaccines were given together with routine Expanded Program on Immunization vaccines. Adverse reactions were recorded after vaccination, and antibody concentrations were measured by enzyme-linked immunosorbent assays. Results. Local induration and tenderness were observed more commonly at the site of injection of TETRAMUNE than at the site of injection with PnCV after each dose of vaccination. Swelling at the site of injection was encountered more frequently at the site of administration of TETRAMUNE than at the site of administration PnCV (P < 0.00001 for Doses 1 and 2 and P < 0.0009 for Dose 3). Swelling at the site of administration of TETRAMUNE mixed with PnCV was comparable with that observed for TETRAMUNE alone. Although most mothers reported that the babies "felt hot" 24 h after each injection, febrile reactions (temperature, ≥38°C) were infrequent and resolved with antipyretics. Geometric mean titer for anti-polyribosylribitol phosphate antibody was 11.6 μg/ml [95% confidence limits (95% CI), 9.2, 14.6] in the control group and comparable with 13.3 μg/ml (95% CI 11.0, 16.0) in the combined group and significantly higher at 17.9 μg/ml (95% CI 14.7, 21.9; P = 0.01) in the separate group. Geometric mean concentrations of serotype-specific pneumococcal antibodies were higher in the combined group than the separate group for all nine serotypes. Antibody responses to diphtheria and pertussis antigens were similar in all groups. Anti-tetanus toxoid antibody concentrations were lowest in the combined group (6.66 IU/ml, 95% CI 5.77, 7.68 in the control group; 5.15 IU/ml, 95% CI 4.39, 6.03 in the combined group; P = 0.02). However, all vaccinees achieved protective antibody values. Conclusion. The combination of TETRAMUNE and PnCV is safe and immunogenic.

AB - Background. Pneumococcal polysaccharide/ protein conjugate vaccines (PnCV) are immunogenic and effective in infancy. However, an addition to the nine currently recommended vaccine injections during the first year of life of African children may be a deterrent to participation in a PnCV program. Thus we have evaluated the safety and immunogenicity of a 9-valent PnCV (Wyeth Lederle Pediatrics and Vaccines) mixed with diphtheria, tetanus toxoid, cell pertussis and Haemophilus influenzae type b (TETRAMUNE). Methods. Healthy Gambian infants were randomized at the age of 2 months to receive three doses 1 month apart of either (1) placebo reconstituted in TETRAMUNE in the right thigh (control) or (2) PnCV in the left thigh and TETRAMUNE in the right thigh (separate) or (3) PnCV reconstituted in TETRAMUNE as a single injection in the right thigh (combined). The vaccines were given together with routine Expanded Program on Immunization vaccines. Adverse reactions were recorded after vaccination, and antibody concentrations were measured by enzyme-linked immunosorbent assays. Results. Local induration and tenderness were observed more commonly at the site of injection of TETRAMUNE than at the site of injection with PnCV after each dose of vaccination. Swelling at the site of injection was encountered more frequently at the site of administration of TETRAMUNE than at the site of administration PnCV (P < 0.00001 for Doses 1 and 2 and P < 0.0009 for Dose 3). Swelling at the site of administration of TETRAMUNE mixed with PnCV was comparable with that observed for TETRAMUNE alone. Although most mothers reported that the babies "felt hot" 24 h after each injection, febrile reactions (temperature, ≥38°C) were infrequent and resolved with antipyretics. Geometric mean titer for anti-polyribosylribitol phosphate antibody was 11.6 μg/ml [95% confidence limits (95% CI), 9.2, 14.6] in the control group and comparable with 13.3 μg/ml (95% CI 11.0, 16.0) in the combined group and significantly higher at 17.9 μg/ml (95% CI 14.7, 21.9; P = 0.01) in the separate group. Geometric mean concentrations of serotype-specific pneumococcal antibodies were higher in the combined group than the separate group for all nine serotypes. Antibody responses to diphtheria and pertussis antigens were similar in all groups. Anti-tetanus toxoid antibody concentrations were lowest in the combined group (6.66 IU/ml, 95% CI 5.77, 7.68 in the control group; 5.15 IU/ml, 95% CI 4.39, 6.03 in the combined group; P = 0.02). However, all vaccinees achieved protective antibody values. Conclusion. The combination of TETRAMUNE and PnCV is safe and immunogenic.

KW - African infant

KW - Immunogenicity

KW - Pneumococcal conjugate vaccine

KW - Safety

KW - TETRAMUNE

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