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: Results from an open-labelled randomized controlled trial in Indian children

Anand Kawade; Girish Dayma; Aditi Apte; Nilima Telang; Meenakshi Satpute; Emma Pearce; Lucy Roalfe; Rakesh Patil; Yanyun Wang; Navideh Noori; Arun Gondhali; Sanjay Juvekar; Assaf P Oron; Sonali Sanghavi; David Goldblatt; Ron Dagan; Ashish Bavdekar

doi:10.1016/j.vaccine.2023.04.008

Effect of reduced two-dose (1+1) schedule of 10 and 13-valent pneumococcal conjugate vaccines (Synflorix^TM and Prevenar13^TM)) on nasopharyngeal carriage and serotype-specific immune response in the first two years of life: Results from an open-labelled randomized controlled trial in Indian children

Vaccine. 2023 May 5;41(19):3066-3079. doi: 10.1016/j.vaccine.2023.04.008. Epub 2023 Apr 10.

Authors

Anand Kawade¹, Girish Dayma², Aditi Apte², Nilima Telang³, Meenakshi Satpute³, Emma Pearce⁴, Lucy Roalfe⁴, Rakesh Patil², Yanyun Wang⁴, Navideh Noori⁵, Arun Gondhali², Sanjay Juvekar², Assaf P Oron⁶, Sonali Sanghavi³, David Goldblatt⁴, Ron Dagan⁷, Ashish Bavdekar⁸

Affiliations

¹ Vadu Rural Health Program, KEM Hospital Research Centre, Pune, India. Electronic address: anand.kawade@kemhrcvadu.org.
² Vadu Rural Health Program, KEM Hospital Research Centre, Pune, India.
³ Department of Microbiology, KEM Hospital, Pune, India.
⁴ Infection, Immunity and Inflammation Department, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
⁵ Institute for Disease Modeling, Global Health Division, Bill and Melinda Gates Foundation, 500 5th Ave N, Seattle, WA, USA.
⁶ Institute for Health Metrics and Evaluation, University of Washington, Seattle, USA.
⁷ The Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
⁸ Vadu Rural Health Program, KEM Hospital Research Centre, Pune, India. Electronic address: a.bavdekar@kemhrcpune.org.

PMID: 37045679
DOI: 10.1016/j.vaccine.2023.04.008

Abstract

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 Synflorix^TM(PCV10) or Prevenar13^TM(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.

Keywords: Pneumococcal carriage; Pneumococcal conjugate vaccines; Reduced dose regime; Serotype-specific antibodies.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Bacterial
Child
Child, Preschool
Humans
Immunity
Infant
Infant, Newborn
Pneumococcal Infections* / prevention & control
Pneumococcal Vaccines
Serogroup
Vaccines, Conjugate

Substances

PHiD-CV vaccine
13-valent pneumococcal vaccine
Antibodies, Bacterial
Pneumococcal Vaccines
Vaccines, Conjugate