scholarly journals Designing ecologically-optimised vaccines using population genomics

2019 ◽  
Author(s):  
Caroline Colijn ◽  
Jukka Corander ◽  
Nicholas J. Croucher
Keyword(s):  
Pneumococcal Disease ◽  
Population Genomics ◽  
Epidemiological Data ◽  
Antibiotic Resistant ◽  
Substantial Impact ◽  
Post Vaccination ◽  
Vaccine Serotypes ◽  
Resistant Disease ◽  
Serotype Replacement ◽  
Polysaccharide Capsules

AbstractStreptococcus pneumoniae (the pneumococcus) is a common nasopharyngeal commensal capable of infecting normally sterile anatomical sites, resulting in invasive pneumococcal disease (IPD). Effective vaccines preventing IPD exist, but each of the antigens they contain typically induces protective immunity against only one of the approximately 100 pneumococcal serotypes, which are differentiated by immunogenically-distinct polysaccharide capsules. Serotypes vary in their propensity to cause IPD, quantified as their invasiveness. Vaccines are designed to include serotypes commonly isolated from IPD, but the immunity they induce is sufficiently strong to also eliminate vaccine serotypes from carriage. This enables their replacement by non-vaccine serotypes in the nasopharynx. The emergence of invasive non-vaccine serotypes has undermined some vaccination programmes’ benefits. Recent advances in genomics and modeling have enabled forecasting of which non-vaccine serotypes will be successful post-vaccination. Here, we demonstrate that vaccines optimised using this framework can minimise IPD and antibiotic-resistant disease more effectively than existing formulations in the model, through mitigating the consequences of serotype replacement. The simulations also demonstrate that tailoring vaccines to the pre-vaccine bacterial population is likely to have a substantial impact on reducing IPD, highlighting the importance of epidemiological data, genomics and ecological models as tools for vaccine design and evaluation.

scholarly journals Divergent serotype replacement trends and increasing diversity in pneumococcal disease in high income settings reduce the benefit of expanding vaccine valency

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alessandra Løchen ◽  
Nicholas J. Croucher ◽  
Roy M. Anderson
Keyword(s):  
Pneumococcal Disease ◽  
Vaccine Uptake ◽  
Partial Replacement ◽  
Age Group ◽  
Serotype Distribution ◽  
Post Vaccination ◽  
Vaccine Serotypes ◽  
European North ◽  
Serotype Replacement ◽  
The Impact

Abstract Streptococcus pneumoniae is a significant cause of otitis media, pneumonia, and meningitis. Only seven of the approximately 100 serotypes were initially included in the pneumococcal polysaccharide conjugate vaccine (PCV) in 2000 before it was expanded in subsequent years. Although the invasive pneumococcal disease (IPD) incidence due to vaccine serotypes (VT) has declined, partial replacement by non-vaccine serotypes (NVT) was observed following widespread vaccine uptake. We conducted a trend analysis assembling the available evidence for PCV impact on European, North American and Australian national IPD. Significant effectiveness against VT IPD in infants was observed, although the impact on national IPD incidence varied internationally due to serotype replacement. Currently, NVT serotypes 8, 9N, 15A and 23B are increasing in the countries assessed, although a variety of other NVTs are affecting each country and age group. Despite these common emerging serotypes, there has not been a dominant IPD serotype post-vaccination as there was pre-vaccination (serotype 14) or post-PCV7 (serotype 19A), suggesting that future vaccines with additional serotypes will be less effective at targeting and reducing IPD in global populations than previous PCVs. The rise of diverse NVTs in all settings’ top-ranked IPD-causing serotypes emphasizes the urgent need for surveillance data on serotype distribution and serotype-specific invasiveness post-vaccination to facilitate decision making concerning both expanding current vaccination programmes and increasing vaccine valency.

scholarly journals Evaluating post-vaccine expansion patterns of pneumococcal serotypes

2020 ◽  
Author(s):  
Maile T. Phillips ◽  
Joshua L. Warren ◽  
Noga Givon-Lavi ◽  
Adrienn Tothpal ◽  
Gili Regev-Yochay ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Invasive Pneumococcal Disease ◽  
Jewish Population ◽  
Pneumococcal Disease ◽  
Pneumococcal Serotypes ◽  
Conjugate Vaccines ◽  
Pneumococcal Conjugate Vaccines ◽  
Vaccine Serotypes ◽  
Serotype Replacement ◽  
Disease Understanding

ABSTRACTStreptococcus pneumoniae remains a leading cause of morbidity and mortality. Pneumococcal conjugate vaccines (PCVs) are effective but target only a fraction of the more than 90 pneumococcal serotypes. As a result, the introduction of PCVs has been followed by the emergence of non-vaccine serotypes. With higher-valency PCVs currently under development, there is a need to understand and predict patterns of serotype replacement to anticipate future changes. In this study, we evaluated patterns of change in serotype prevalence post-PCV introduction in Israel. We found that the assumption that non-vaccine serotypes increase by the same proportion overestimates changes in serotype prevalence in Jewish and Bedouin children. Furthermore, pre-vaccine prevalence was positively associated with increases in prevalence over the study period. From our analyses, serotypes 12F, 8, 16F, 33F, 9N, 7B, 10A, 22F, 24F, and 17F were estimated to have gained the most cases of invasive pneumococcal disease through serotype replacement in the Jewish population. However, this model also failed to quantify some additional cases gained, suggesting that changes in carriage in children alone may be insufficient to explain serotype replacement in disease. Understanding of serotype replacement is important as higher-valency vaccines are introduced.

scholarly journals Invasive pneumococcal disease in Latvia seven years after PCV10 introduction

2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
L Savrasova ◽  
I Zeltina ◽  
A Villerusha ◽  
S Balasegaram
Keyword(s):  
Invasive Pneumococcal Disease ◽  
Pneumococcal Disease ◽  
Case Fatality ◽  
Annual Incidence ◽  
Surveillance Data ◽  
Serotype Distribution ◽  
Vaccine Serotypes ◽  
Serotype Replacement ◽  
Increasing Trend ◽  
And Control

Abstract Background In 2009 in Latvia, invasive pneumococcal disease (IPD) became notifiable for physicians and in 2010 vaccination of infants with PCV7 commenced. In 2012 PCV10 vaccination was introduced. The objectives of our study were to evaluate trend of incidence and trend serotype distribution of IPD in Latvia and to investigate factors associated with death from IPD. Methods Laboratory confirmed IPD cases are passively notified to the Centre for Disease Prevention and Control of Latvia by laboratories and clinicians. We calculated incidence by age, sex, case fatality and trend in serotypes. Results From 2012 to 2018, 466 cases of IPD were reported, mean annual incidence 3.4/100,000. The notified incidence remained stable from 2012-2014 (2.7), peaked in 2015 (4.4) and fell to 3.9 in 2018. The highest mean annual IPD incidence was in infants (4.8) and in elderly (6). The highest mean annual incidence was reported in males (4.5) in comparison to females (2.4) (IR-1.8 95%CI 1.6-2.4). Case fatality was 19% (87/466) and 23% (37/162) in cases aged > =65 years. 90% (421/466) of isolates were serotyped. The proportion of PCV10 vaccine serotypes fell from 50% (20/40) in 2012 to 19% (14/74) in 2018 (chi2 test for trend =0.000). Since year 2017, PPV23nonPCV13 and Non-vaccine serotypes become more common. We detected PCV13 serotype (RR 2.04 95%CI 1.37-3.02), S.pneumoniae serotype 3 (RR 1. 91 95% CI 1.25-2.93) significantly associated with IPD death. Conclusions Surveillance data indicate evidence of serotype replacement. Surveillance evaluation should asses the representativeness of notification. Furthermore S. pneumoniae carriage study may be useful to characterise serotype circulation. Serotype 3 and age demonstrate independent and significant association with fatal IPD outcome. Key messages IPD surveillance data analysis indicated evidence of serotype replacement with PPV23nonPCV13, NonVaccine serotypes. Serotype 19A becomes more common with significant increasing trend. Serotype 3 and age independently and significantly associated with fatal IPD outcome. S.pneumoniae carriage study would be very useful providing more evidence of characterizing serotypes circulation.

scholarly journals Salmonella enterica Subsp. houtenae Associated with an Abscess in Young Roe Deer (Capreolus capreolus)

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 654
Author(s):  
Adriana Trotta ◽  
Laura Del Sambro ◽  
Michela Galgano ◽  
Stefano Ciccarelli ◽  
Erika Ottone ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Roe Deer ◽  
Capreolus Capreolus ◽  
Epidemiological Data ◽  
Resistance Pattern ◽  
Salmonella Spp ◽  
Antibiotic Resistant ◽  
Biochemical Identification ◽  
Salmonella Pathogenicity Islands ◽  
Insight Into

Background: S. enterica subsp. houtenae has been rarely documented, and very limited genomic information is available. This report describes a rare case of primary extraintestinal salmonellosis in a young roe deer, associated with Salmonella enterica subsp. houtenae. Methods: A traditional cultural-based analysis was carried out from the contents of a neck abscess; biochemical identification and PCR assay were performed to isolate and identify the pathogen. Through whole-genome sequencing (WGS), multilocus sequence typing (MLST), core genome MLST (cgMLST), and the Salmonella pathogenicity islands (SPIs) survey, resistome and virulome genes were investigated to gain insight into the virulence and antimicrobial resistance of S. houtenae. Results: Biochemical identification and PCR confirmed the presence of Salmonella spp. in the swelling. The WGS analysis identified Salmonella enterica subspecies houtenae serovar 43:z4,z23:- and ST 958. The virulence study predicted a multidrug resistance pattern with resistance shown against aminoglycosides, tetracycline, beta-lactamase, fluoroquinolones, fosfomycin, nitroimidazole, aminocoumarin, and peptide. Fifty-three antibiotic-resistant genes were identified. No plasmids were detected. Conclusion: This study demonstrates the importance of continuous surveillance of pathogenic salmonellae. Biomolecular analyses combined with epidemiological data can provide important information about poorly described Salmonella strains and can help to improve animal welfare.

scholarly journals Postvaccination Increase in Serotype 19A Pneumococcal Disease in Norway Is Driven by Expansion of Penicillin-Susceptible Strains of the ST199 Complex

2012 ◽  
Vol 19 (3) ◽  
pp. 443-445 ◽  
Author(s):  
Didrik F. Vestrheim ◽  
Martin Steinbakk ◽  
Ingeborg S. Aaberge ◽  
Dominique A. Caugant
Keyword(s):  
Conjugate Vaccine ◽  
Invasive Pneumococcal Disease ◽  
Pneumococcal Conjugate Vaccine ◽  
Selection Pressure ◽  
Pneumococcal Disease ◽  
Antibiotic Selection ◽  
Serotype Replacement ◽  
Rapid Replacement ◽  
Antibiotic Selection Pressure

ABSTRACTSerotype replacement in invasive pneumococcal disease has been observed after widespread use of the 7-valent pneumococcal conjugate vaccine (PCV7). Replacement is dominated by penicillin-nonsusceptible serotype 19A in several countries. Antibiotic selection pressure has been proposed to interact with immunization, leading to rapid replacement. In Norway, where prescription of antibiotics is limited, post-PCV7 replacement by serotype 19A is dominated by penicillin-susceptible clones. Hence, serotype 19A replacement occurs, although it is not driven by antibiotic selection pressure.

scholarly journals Early signals of vaccine driven perturbation seen in pneumococcal carriage population genomic data

2018 ◽  
Author(s):  
Chrispin Chaguza ◽  
Ellen Heinsbroek ◽  
Rebecca A. Gladstone ◽  
Terence Tafatatha ◽  
Maaike Alaerts ◽  
...  
Keyword(s):  
Population Structure ◽  
Mobile Genetic Elements ◽  
Post Vaccination ◽  
Accessory Genome ◽  
Genetic Elements ◽  
Genomic Level ◽  
Accessory Genes ◽  
Serotype Replacement ◽  
Vaccine Type ◽  
Genome Level

AbstractPneumococcal conjugate vaccines (PCV) have reduced pneumococcal diseases globally. Despite this, much remains to be learned about their effect on pathogen population structure. Here we undertook whole genome sequencing of 660 pneumococcal strains from asymptomatic carriers to investigate population restructuring in pneumococcal strains sampled before and after PCV13 introduction in a previously vaccine-naïve setting. We show substantial decreasing frequency of vaccine-type (VT) strains and their strain diversity post-vaccination in the vaccinated but not unvaccinated age groups indicative of direct but limited or delayed indirect effect of vaccination. Clearance of identical VT serotypes associated with multiple lineages occurred regardless of their genetic background. Interestingly, despite the increasing frequency of non-vaccine type (NVT) strains through serotype replacement, the serotype diversity was not fully restored to the levels observed prior to vaccination implying limited serotype replacement. The frequency of antibiotic resistant strains was low and remained largely unchanged post-vaccination but intermediate-penicillin-resistant lineages were reduced in the post vaccine population. Significant perturbations marked by changing frequency of accessory genes associated with diverse functions especially mobile genetic elements and bacteriocin activity were detected. This phylogenomic analysis demonstrates early vaccine-induced pneumococcal population restructuring not only at serotype but also accessory genome level.Author summaryDifferent formulations of PCVs have been effective in reducing the invasive pneumococcal disease burden globally. Clinical trials have started to indicate high impact and effectiveness of PCV13 in Sub Saharan Africa (SSA) but there is limited understanding of how the introduction of PCVs alters the population structure of pneumococcal strains at serotype and genomic level. Here we investigated this using pneumococcal strains sampled pre‐ and post-PCV13 introduction from a previously vaccine naïve setting in Northern Malawi. Our findings reveal decrease in frequency of VT serotypes and their associated lineages in the largely vaccinated under-five population but not older individuals indicating a direct but limited or delayed indirect protection. The diversity of serotypes also decreased post-vaccination in VT strains in the under-fives but there was no change in NVT strains suggesting incomplete serotype replacement. At the genomic level, logistic regression revealed changing frequency of accessory genes largely associated with mobile genetic elements but such changes did not include any antibiotic resistance genes. These findings show significant perturbations at serotype and accessory genome level in carried pneumococcal population after two years from PCV13 introduction but the pneumococcal population was still perturbed and had not returned to a new equilibrium state.

scholarly journals Three Cases of Invasive Pneumococcal Disease with Multiple Serotype Replacement in Vaccinated Children

2017 ◽  
Vol 76 (5) ◽  
pp. 215-217
Author(s):  
Naohide Kin ◽  
Mamoru Ayusawa ◽  
Nobuhiko Nagano ◽  
Ryuta Yonezawa ◽  
Maki Furukawa ◽  
...  
Keyword(s):  
Invasive Pneumococcal Disease ◽  
Pneumococcal Disease ◽  
Serotype Replacement

scholarly journals Substantial impact of post-vaccination contacts on cumulative infections during viral epidemics

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 315
Author(s):  
Nash Rochman ◽  
Yuri Wolf ◽  
Eugene V. Koonin
Keyword(s):  
Deterministic Model ◽  
Vaccination Campaign ◽  
Current Status ◽  
Distribution Analysis ◽  
Cumulative Number ◽  
Optimal Distribution ◽  
Substantial Impact ◽  
Post Vaccination ◽  
Novel Coronavirus ◽  
Susceptible Populations

Background: The start of 2021 was marked by the initiation of a global vaccination campaign against the novel coronavirus SARS-CoV-2. Formulating an optimal distribution strategy under social and economic constraints is challenging. Optimal distribution is additionally constrained by the potential emergence of vaccine resistance. Analogous to chronic low-dose antibiotic exposure, recently inoculated individuals who are not yet immune play an outsized role in the emergence of resistance. Classical epidemiological modelling is well suited to explore how the behavior of the inoculated population impacts the total number of infections over the entirety of an epidemic. Methods: A deterministic model of epidemic evolution is analyzed, with seven compartments defined by their relationship to the emergence of vaccine-resistant mutants and representing three susceptible populations, three infected populations, and one recovered population. This minimally computationally intensive design enables simulation of epidemics across a broad parameter space. The results are used to identify conditions minimizing the cumulative number of infections. Results: When an escape variant is only modestly less infectious than the originating strain within a naïve population, the cumulative number of infections does not monotonically decrease with the rate of vaccine distribution. Analysis of the model also demonstrates that inoculated individuals play a major role in the mitigation or exacerbation of vaccine-resistant outbreaks. Modulating the rate of host–host contact for the inoculated population by less than an order of magnitude can alter the cumulative number of infections by more than 20%. Conclusions: Mathematical modeling shows that limiting post-vaccination contacts can perceptibly affect the course of an epidemic. The consideration of limitations on post-vaccination contacts remains relevant for the entire duration of any vaccination campaign including the current status of SARS-CoV-2 vaccination.

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