# Non-Vaccine Serotype Replacement and Subdominant Persistence of Vaccine Types in Nepalese Infants Following PCV10 Introduction

## TL;DR

A study in Nepal found that while a pneumococcal vaccine reduced certain bacteria types, other non-vaccine types became dominant, highlighting the need for updated vaccines and interventions.

## Contribution

The study reveals subdominant persistence of vaccine types and rapid dominance of non-vaccine serotypes following PCV10 introduction in Nepalese infants.

## Key findings

- PCV10 reduced vaccine-type carriage from 32.8% to 4.8% in 12 months.
- Non-vaccine serotypes like 35B and 19A became dominant after vaccine types declined.
- Older infants and winter seasons were significant risk factors for pneumococcal carriage.

## Abstract

Background: Streptococcus pneumoniae is a leading cause of child mortality in Nepal despite the introduction of the 10-valent pneumococcal conjugate vaccine (PCV10). Vaccine effectiveness is threatened by the emergence of non-vaccine serotypes (NVTs) and the multiple serotypes carriage which often fail to be detected by traditional methods. We aimed to study changes in serotype distribution before and after PCV10 immunization among infants, including serotype dominance in Nepalese infants in the post-vaccine era. Methods: We enrolled infants in a longitudinal cohort study (2020–2022) conducted in Bhaktapur, Nepal. Nasopharyngeal swabs were collected before PCV10 dose 1 (6 weeks) and at 9 and 12 months post-immunization. We used a sensitive nanofluidic qPCR platform to detect multiple serotypes and establish their hierarchy by quantifying the bacterial load of each strain. Inverse Probability Weighting (IPW) adjusted risk factor analysis was used to account for loss to follow-up. Results: PCV10 successfully reduced vaccine-type (VT) carriage, declining sharply from 32.8% at 6 weeks to 4.8% at 12 months. VTs were pushed from being the dominant strain to occupying subdominant roles in co-colonization. Conversely, NVTs rapidly filled the vacated niche, showing a significant increase in their dominant status (p < 0.001). The most common replacing NVTs that rose to dominance were 35B, 19A, 6C/6D, and 15B/15C. Significant risk factors for carriage included older infancy (aOR 3.4, 95%CI: 2.6–4.5 at 9 months), a household kitchen in the living area (aOR 1.4, 95%CI: 1.0–1.9), and winter (aOR 1.7, 95%CI: 1.5–2.7) and pre-monsoon seasons (aOR 2.0, 95%CI: 1.5–2.8). Conclusions: While PCV10 reduced overall VT circulation, the persistence of VTs in subdominant niches creates a continuous reservoir for potential re-emergence and antibiotic resistance. This clear hierarchical shift in dominance towards NVTs underscores the urgent need for a public health strategy that includes the adoption of a higher-valent PCV to provide broader protection, and interventions targeting environmental risk factors are essential to sustain long-term reductions in pneumococcal colonization.