Andrea Gori, United Kingdom

University College London Infection and Immunity

Presenter of 2 Presentations

 Conference Calendar

THE EMERGENCE OF A STREPTOCOCCUS PNEUMONIAE SEROTYPE 3 VARIANT CARRIAGE IN THE 8 YEARS FOLLOWING POST-PCV13 INTRODUCTION IN BLANTYRE, MALAWI. (ID 606)

Session Name
Basic Sciences - Genomics and Transmission
Presenter
Authors

Abstract

Background

Several studies have demonstrated limited PCV13 efficacy against carriage of serotype 3 Streptococcus pneumoniae. In Blantyre, no direct vaccine effect was identified on serotype 3 carriage 8 years after PCV13 introduction, and population-based serology showed limited induction of serotype 3-specific antibodies by vaccine or natural exposure. We hypothesised that sequence variability of the CPS locus could at least partly explain these observations.

Methods

CPS loci of 540 serotype 3 isolates (from Africa, Asia, Europe and America) were analysed. ML-phylogeny, antimicrobial resistance (tetM, mefA, ermB, cat gene presence and pbpX allelic profiles) and MLST were calculated. Colony morphology was assessed in microaerophilic and anaerobic conditions.

Results

We identified a serotype 3 CPS locus variant in 82% of Blantyre isolates (2015-2019), characterized by an 8-gene cluster deletion but unchanged colony morphology. This variant appeared independently in at least 3 distinct phylogenetic clusters, including ST700 and ST3214. These strains are characterised by the presence of AMR genes and higher MIC to penicillin. The missing CPS genes have hypothetical protein annotation.

Conclusions

This CPS variant segregated with an AMR genotype, which may have contributed to its emergence. Whether this CPS variation will influence immunogenicity remains to be determined.

Hide

INCREASE IN FREQUENCY OF PNEUMOCOCCAL METABOLIC GENOTYPES CHARACTERISED BY ANTIMICROBIAL RESISTANCE AND ADAPTATIONS FOR COLONIZATION AFTER PCV13 INTRODUCTION IN BLANTYRE, MALAWI. (ID 416)

Session Name
Vaccines - Impact of Vaccine programs and Serotype Replacement
Presenter
Authors

Abstract

Background

Streptococcus pneumoniae naturally undergoes fluctuations in genotype. We previously showed a high residual prevalence of vaccine serotype (VT) pneumococci (18% in under 5’s) 7 years after PCV13 introduction in Malawi. In this context, we hypothesised the emergence and fixation of S. pneumoniae lineages with genetic traits conveying a competitive advantage in the nasopharyngeal niche.

Methods

1826 S. pneumoniae genomes were analysed from isolates collected during rolling cross-sectional carriage surveys in Blantyre, 4-7 years after PCV13 introduction. The metabolic core-genome includes 175 discrete metabolic genotypic profiles (metabolic types, MTs). Relative fitness was assessed by in-vitro growth and adhesive potential evaluated using Detroit 562 nasopharyngeal epithelial cells.

Results

High residual pneumococcal carriage is characterised by persistent MTs in VT (e.g. 3 and 23F) and emerging new MTs in non-VT (NVT; 38 and 23B). Increase in AMR MTs among 38 and 23B was observed. Emerging MTs show characteristic sequences of virulence genes and are characterised phenotypically by higher growth potential and propensity for better adherence to NP cell. We identified convergent evolution between MTs isolated in different countries, result of genetic bottlenecks.

Conclusions

This shift in metabolic genotypes, antimicrobial resistance and colonization adaptations may facilitate vaccine escape.

Hide

Author Of 4 Presentations

 Conference Calendar

STREPTOCOCCUS PNEUMONIAE VACCINE SEROTYPES ACQUIRE PENICILLIN BINDING PROTEIN GENE MOSAICS FROM STREPTOCOCCUS MITIS (ID 428)

Session Name
Basic Sciences - Genomics and Transmission
Presenter
Authors

THE EMERGENCE OF A STREPTOCOCCUS PNEUMONIAE SEROTYPE 3 VARIANT CARRIAGE IN THE 8 YEARS FOLLOWING POST-PCV13 INTRODUCTION IN BLANTYRE, MALAWI. (ID 606)

Session Name
Basic Sciences - Genomics and Transmission
Presenter
Authors

Abstract

Background

Several studies have demonstrated limited PCV13 efficacy against carriage of serotype 3 Streptococcus pneumoniae. In Blantyre, no direct vaccine effect was identified on serotype 3 carriage 8 years after PCV13 introduction, and population-based serology showed limited induction of serotype 3-specific antibodies by vaccine or natural exposure. We hypothesised that sequence variability of the CPS locus could at least partly explain these observations.

Methods

CPS loci of 540 serotype 3 isolates (from Africa, Asia, Europe and America) were analysed. ML-phylogeny, antimicrobial resistance (tetM, mefA, ermB, cat gene presence and pbpX allelic profiles) and MLST were calculated. Colony morphology was assessed in microaerophilic and anaerobic conditions.

Results

We identified a serotype 3 CPS locus variant in 82% of Blantyre isolates (2015-2019), characterized by an 8-gene cluster deletion but unchanged colony morphology. This variant appeared independently in at least 3 distinct phylogenetic clusters, including ST700 and ST3214. These strains are characterised by the presence of AMR genes and higher MIC to penicillin. The missing CPS genes have hypothetical protein annotation.

Conclusions

This CPS variant segregated with an AMR genotype, which may have contributed to its emergence. Whether this CPS variation will influence immunogenicity remains to be determined.

Hide

MODELLING POST-PCV13 SEROTYPE-SPECIFIC ANTI-CAPSULAR AND ANTI-PROTEIN IGG RESPONSES IN BLANTYRE, MALAWI. (ID 989)

Session Name
Population Sciences - Epidemiology, Economics, and Mathematical Modelling
Presenter
Authors

INCREASE IN FREQUENCY OF PNEUMOCOCCAL METABOLIC GENOTYPES CHARACTERISED BY ANTIMICROBIAL RESISTANCE AND ADAPTATIONS FOR COLONIZATION AFTER PCV13 INTRODUCTION IN BLANTYRE, MALAWI. (ID 416)

Session Name
Vaccines - Impact of Vaccine programs and Serotype Replacement
Presenter
Authors

Abstract

Background

Streptococcus pneumoniae naturally undergoes fluctuations in genotype. We previously showed a high residual prevalence of vaccine serotype (VT) pneumococci (18% in under 5’s) 7 years after PCV13 introduction in Malawi. In this context, we hypothesised the emergence and fixation of S. pneumoniae lineages with genetic traits conveying a competitive advantage in the nasopharyngeal niche.

Methods

1826 S. pneumoniae genomes were analysed from isolates collected during rolling cross-sectional carriage surveys in Blantyre, 4-7 years after PCV13 introduction. The metabolic core-genome includes 175 discrete metabolic genotypic profiles (metabolic types, MTs). Relative fitness was assessed by in-vitro growth and adhesive potential evaluated using Detroit 562 nasopharyngeal epithelial cells.

Results

High residual pneumococcal carriage is characterised by persistent MTs in VT (e.g. 3 and 23F) and emerging new MTs in non-VT (NVT; 38 and 23B). Increase in AMR MTs among 38 and 23B was observed. Emerging MTs show characteristic sequences of virulence genes and are characterised phenotypically by higher growth potential and propensity for better adherence to NP cell. We identified convergent evolution between MTs isolated in different countries, result of genetic bottlenecks.

Conclusions

This shift in metabolic genotypes, antimicrobial resistance and colonization adaptations may facilitate vaccine escape.

Hide