TY - JOUR
T1 - Effect of reduced two-dose (1+1) schedule of 10 and 13-valent pneumococcal conjugate vaccines (SynflorixTM and Prevenar13TM)) on nasopharyngeal carriage and serotype-specific immune response in the first two years of life
T2 - Results from an open-labelled randomized controlled trial in Indian children
AU - Kawade, Anand
AU - Dayma, Girish
AU - Apte, Aditi
AU - Telang, Nilima
AU - Satpute, Meenakshi
AU - Pearce, Emma
AU - Roalfe, Lucy
AU - Patil, Rakesh
AU - Wang, Yanyun
AU - Noori, Navideh
AU - Gondhali, Arun
AU - Juvekar, Sanjay
AU - Oron, Assaf P.
AU - Sanghavi, Sonali
AU - Goldblatt, David
AU - Dagan, Ron
AU - Bavdekar, Ashish
N1 - Funding Information:
We would like to thank the following members from the Vadu Rural Health Program of KEM Hospital Research Centre, Pune: Dr Dhiraj Agarwal for his help in the storage and transportation of laboratory samples; Shriram Sadafal for data management; Tathagata Bhattacharjee and Sandeep Bhujbal for designing the electronic case record forms. We are grateful to Dr Sameer Saha and his team from Child Health Research Foundation for their continuous support in training and validating laboratory processes for nasopharyngeal specimen testing. We are thankful to Dr V. Balaji and his team from the Microbiology Department, Christian Medical College, Vellore for their support in external quality assurance for the analysis of nasopharyngeal specimens for S. pneumoniae. We would like to thank all the field and laboratory research assistants from Vadu Rural Health Program who helped in the data acquisition. We are in debt to all the study participants and their family members for agreeing to participate in this study and providing their valuable data.
Funding Information:
The study was supported by a grant from the Bill and Melinda Gates Foundation and KEM Hospital Research Centre, Pune was a sub-recipient to RFA 2014-1 through the INCLEN Trust International, New Delhi, India. The immunobiology unit at University College London is part supported by the NIHR Great Ormond Street Biomedical Research Centre.
Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/5/5
Y1 - 2023/5/5
N2 - Introduction: This study aimed to assess the effect of a reduced dose regime (1 + 1) of PCV10 and PCV13 along with 3-dose regimes on pneumococcal vaccine-type (VT) carriage and immunogenicity in the first two years of life in PCV-naïve Indian children. Methods: A total of 805 healthy infants aged 6–8 weeks were randomised to 7 groups (n = 115). Six groups received SynflorixTM(PCV10) or Prevenar13TM(PCV13) in the following schedules: 3 + 0 (three primary at 6, 10, and 14 weeks); 2 + 1 (two primary 6 and 14 weeks with booster at 9 months; 1 + 1 (one primary at 14 weeks with booster at 9 months). The 7th group was a PCV-naïve control group. Nasopharyngeal swabs were collected at 6, 18 weeks, 9, 10, 15, and 18 months of age. Venous blood samples were collected at 18 weeks, 9, 10, and 18 months of age for assessment of sero-specific IgG antibodies. Additionally, functional activity using a serotype specific opsonophagocytic assay (OPA) was assessed at 10 and 18 months of age in a subset (20%) of participants. Results: All schedules of PCV13 showed significant 13VT carriage reduction in the second year of life as compared to control. At 15 months of age, PCV13 (1 + 1) showed 45 % reduction in 13VT-carriage compared to the control [OR = 0.55 (95% CI; 0.31–0.97), p= 0.038]. None of the PCV10 schedules showed significant reduction in 10VT carriage in the second year. Although not powered for these outcomes, at 18 months of age, 1 + 1 and 2 + 1 schedules of both vaccines demonstrated higher sero-responders for all serotypes, higher geometric mean concentrations (GMC) for all serotypes except 23F [with both vaccines], higher percent OPA responders and OPA geometric mean titres (GMT) compared to the 3 + 0 schedules for all serotypes. Conclusion: The reduced dose schedule (1 + 1) of PCV13 results in significant VT-carriage reduction in the second year of life. Immune protection provided by 1 + 1 schedules of PCV10 and PCV13 in the second year of life is comparable to WHO-recommended 3-dose schedules.
AB - Introduction: This study aimed to assess the effect of a reduced dose regime (1 + 1) of PCV10 and PCV13 along with 3-dose regimes on pneumococcal vaccine-type (VT) carriage and immunogenicity in the first two years of life in PCV-naïve Indian children. Methods: A total of 805 healthy infants aged 6–8 weeks were randomised to 7 groups (n = 115). Six groups received SynflorixTM(PCV10) or Prevenar13TM(PCV13) in the following schedules: 3 + 0 (three primary at 6, 10, and 14 weeks); 2 + 1 (two primary 6 and 14 weeks with booster at 9 months; 1 + 1 (one primary at 14 weeks with booster at 9 months). The 7th group was a PCV-naïve control group. Nasopharyngeal swabs were collected at 6, 18 weeks, 9, 10, 15, and 18 months of age. Venous blood samples were collected at 18 weeks, 9, 10, and 18 months of age for assessment of sero-specific IgG antibodies. Additionally, functional activity using a serotype specific opsonophagocytic assay (OPA) was assessed at 10 and 18 months of age in a subset (20%) of participants. Results: All schedules of PCV13 showed significant 13VT carriage reduction in the second year of life as compared to control. At 15 months of age, PCV13 (1 + 1) showed 45 % reduction in 13VT-carriage compared to the control [OR = 0.55 (95% CI; 0.31–0.97), p= 0.038]. None of the PCV10 schedules showed significant reduction in 10VT carriage in the second year. Although not powered for these outcomes, at 18 months of age, 1 + 1 and 2 + 1 schedules of both vaccines demonstrated higher sero-responders for all serotypes, higher geometric mean concentrations (GMC) for all serotypes except 23F [with both vaccines], higher percent OPA responders and OPA geometric mean titres (GMT) compared to the 3 + 0 schedules for all serotypes. Conclusion: The reduced dose schedule (1 + 1) of PCV13 results in significant VT-carriage reduction in the second year of life. Immune protection provided by 1 + 1 schedules of PCV10 and PCV13 in the second year of life is comparable to WHO-recommended 3-dose schedules.
KW - Pneumococcal carriage
KW - Pneumococcal conjugate vaccines
KW - Reduced dose regime
KW - Serotype-specific antibodies
UR - http://www.scopus.com/inward/record.url?scp=85152387538&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2023.04.008
DO - 10.1016/j.vaccine.2023.04.008
M3 - Article
C2 - 37045679
AN - SCOPUS:85152387538
SN - 0264-410X
VL - 41
SP - 3066
EP - 3079
JO - Vaccine
JF - Vaccine
IS - 19
ER -
