Immunogenicity, safety, and tolerability of 13-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine in recipients of allogeneic hematopoietic stem cell transplant aged ≥2 years: an open-label study.

Abstract

BACKGROUND:

Life-threatening Streptococcus pneumoniae infections often occur after hematopoietic stem cell transplant (HSCT); vaccination is important for prevention.

METHODS:

In an open-label study, patients (n = 251) 3-6 months after allogeneic HSCT received 3 doses of 13-valent pneumococcal conjugate vaccine (PCV13) at 1-month intervals, a fourth dose 6 months later, and 1 dose of 23-valent pneumococcal polysaccharide vaccine (PPSV23) 1 month later. Immunogenicity at prespecified time points and vaccine safety were assessed.

RESULTS:

In the evaluable immunogenicity population (N = 216; mean age, 37.8 years), geometric mean fold rises (GMFRs) of immunoglobulin G geometric mean concentrations from baseline to postdose 3 showed significant increases in antibody levels across all PCV13 serotypes (GMFR range, 2.99-23.85; 95% confidence interval lower limit, >1); there were significant declines over the next 6 months, significant increases from predose 4 to postdose 4 (GMFR range, 3.00-6.97), and little change after PPSV23 (GMFR range, 0.86-1.12). Local and systemic reactions were more frequent after dose 4. Six patients experienced serious adverse events possibly related to PCV13 (facial diplegia, injection-site erythema and pyrexia, autoimmune hemolytic anemia, and suspected lack of vaccine efficacy after dose 3 leading to pneumococcal infection), PCV13 and PPSV23 (Guillain-Barré syndrome), or PPSV23 (cellulitis). There were 14 deaths, none related to study vaccines.

CONCLUSIONS:

A 3-dose PCV13 regimen followed by a booster dose may be required to protect against pneumococcal disease in HSCT recipients. Dose 4 was associated with increased local and systemic reactions, but the overall safety profile of a 4-dose regimen was considered acceptable.

CLINICAL TRIALS REGISTRATION:

NCT00980655.

• Authors: Catherine Cordonnier, Per Ljungman, Christine Juergens, Johan Maertens, Dominik Selleslag, Vani Sundaraiyer, Peter C Giardina, Keri Clarke, William C Gruber, Daniel A Scott, Beate Schmoele-Thoma, 3003 Study Group
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 61 Issue 3 Pg. 313-23 (Aug 01 2015) ISSN: 1537-6591 [Electronic] United States
• PMID: 25870329 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Chemical References

• 13-valent pneumococcal vaccine
• 23-valent pneumococcal capsular polysaccharide vaccine
• Antibodies, Bacterial
• Immunoglobulin G
• Pneumococcal Vaccines

Topics

• Adolescent
• Antibodies, Bacterial (blood)
• Child
• Child, Preschool
• Female
• Hematopoietic Stem Cell Transplantation (statistics & numerical data)
• Humans
• Immunoglobulin G (blood)
• Male
• Pneumococcal Infections (immunology, prevention & control)
• Pneumococcal Vaccines (adverse effects, immunology)