scholarly journals Efficacy of a Protein Vaccine and a Conjugate Vaccine Against Co-Colonization with Vaccine-Type and Non-Vaccine Type Pneumococci in Mice

Pathogens ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 278
Author(s):  
Gabriela B. C. Colichio ◽  
Giuliana S. Oliveira ◽  
Tasson C. Rodrigues ◽  
Maria Leonor S. Oliveira ◽  
Eliane N. Miyaji
Keyword(s):  
No Reduction ◽  
Protein A ◽  
Surface Protein ◽  
Protein Formulation ◽  
Protein Vaccine ◽  
Conjugate Vaccines ◽  
Serotype Replacement ◽  
Vaccine Type ◽  
Pneumococcal Serotype ◽  
Low Levels

Widespread use of pneumococcal conjugate vaccines (PCVs) has led to substitution of vaccine-type (VT) strains by non-vaccine type (NVT) strains in nasopharyngeal carriage. We compared the efficacy of PCV13 and a nasal protein formulation containing pneumococcal surface protein A (PspA) adjuvanted with the whole-cell pertussis vaccine (wP) in the protection against co-colonization challenge models in mice with VT and NVT strains expressing different PspAs. Immunized mice were challenged with two different mixtures: i. VT4 (PspA3) + NVT33 (PspA1) and ii. VT23F (PspA2) + NVT15B/C (PspA4). Results from the first mixture showed a reduction in loads of VT4 strain in the nasopharynx of mice immunized with PCV13. A statistical difference between the loads of the VT and NVT strains was observed, indicating a competitive advantage for the NVT strain in PCV13-immunized animals. In the second mixture, no reduction was observed for the VT23F strain, probably due to low levels of anti-23F polysaccharide IgG induced by PCV13. Interestingly, a combination of the PspA formulation containing wP with PCV13 led to a reduction in colonization with both strains of the two mixtures tested, similar to the groups immunized nasally with wP or PspA plus wP. These results indicate that a combination of vaccines may be a useful strategy to overcome pneumococcal serotype replacement.

scholarly journals PspA Family Distribution, unlike Capsular Serotype, Remains Unaltered following Introduction of the Heptavalent Pneumococcal Conjugate Vaccine

2012 ◽  
Vol 19 (6) ◽  
pp. 891-896 ◽  
Author(s):  
Christina M. Croney ◽  
Mamie T. Coats ◽  
Moon H. Nahm ◽  
David E. Briles ◽  
Marilyn J. Crain
Keyword(s):  
Pneumococcal Disease ◽  
Protein A ◽  
Surface Protein ◽  
The United States ◽  
Pediatric Hospital ◽  
Protein Antigens ◽  
Conjugate Vaccines ◽  
Reactive Protein ◽  
Serotype Replacement ◽  
Heptavalent Pneumococcal Conjugate Vaccine

ABSTRACTPneumococcal conjugate vaccines (PCVs) are recommended for the prevention of invasive pneumococcal disease (IPD) in young children. Since the introduction of the heptavalent pneumococcal vaccine (PCV7) in 2000, IPD caused by serotypes in the vaccine has almost been eliminated, and previously uncommon capsular serotypes now cause most cases of pediatric IPD in the United States. One way to protect against these strains would be to add cross-reactive protein antigens to new vaccines. One such protein is pneumococcal surface protein A (PspA). Prior to 2000, PspA families 1 and 2 were expressed by 94% of isolates. Because PCV7 vaccine pressure has resulted in IPD caused by capsular serotypes that were previously uncommon and unstudied for PspA expression, it was possible that many of the new strains expressed different PspA antigens or even lacked PspA. Of 157 pediatric invasive pneumococcal isolates collected at a large pediatric hospital in Alabama between 2002 and 2010, only 60.5% had capsular serotypes included in PCV13, which came into general use in Alabama after our strains were collected. These isolates included 17 serotypes that were not covered by PCV13. Nonetheless, pneumococcal capsular serotype replacement was not associated with changes in PspA expression; 96% of strains in this collection expressed PspA family 1 or 2. Continued surveillance will be critical to vaccine strategies to further reduce IPD.

scholarly journals A mathematical model of serotype replacement in pneumococcal carriage following vaccination

2013 ◽  
Vol 10 (89) ◽  
pp. 20130786 ◽  
Author(s):  
Christian Bottomley ◽  
Anna Roca ◽  
Philip C. Hill ◽  
Brian Greenwood ◽  
Valerie Isham
Keyword(s):  
Mathematical Model ◽  
Childhood Vaccination ◽  
Parameter Estimates ◽  
Conjugate Vaccines ◽  
Partial Protection ◽  
Pneumococcal Carriage ◽  
Serotype Replacement ◽  
Vaccine Type ◽  
Low Prevalence ◽  
The Impact

A number of childhood vaccination programmes have recently introduced vaccination against Streptococcus pneumoniae , the pneumococcus, a major cause of pneumonia and meningitis. The pneumococcal conjugate vaccines (PCVs) that are currently in use only protect against some serotypes of the bacterium, and there is now strong evidence that those serotypes not included in the vaccine increase in prevalence among most vaccinated populations. We present a mathematical model for the dynamics of nasopharyngeal carriage of S. pneumoniae that allows for carriage with multiple serotypes. The model is used to predict the prevalence of vaccine type (VT) and non-VT (NVT) serotypes following the introduction of PCV. Parameter estimates for the model are obtained by maximum likelihood using pre-vaccination data from The Gambia. The model predicts that low (1, 6A and 9V) and medium (4, 5, 7F, 14, 18C, 19A and 19F) prevalence serotypes can be eliminated through vaccination, but that the overall prevalence of carriage will be reduced only slightly because of an increase in the prevalence of NVT serotypes. Serotype replacement will be sequential, with high and medium prevalence NVT serotypes dominating initially, followed by an increase of serotypes of low prevalence. We examine the impact of a hypothetical vaccine that provides partial protection against all serotypes, and find that this reduces overall carriage, but is unable to eliminate low or medium prevalence serotypes.

scholarly journals Broadly reactive human monoclonal antibodies targeting the pneumococcal histidine triad protein protect against fatal pneumococcal infection

2021 ◽  
Author(s):  
Jiachen Huang ◽  
Aaron D. Gingerich ◽  
Fredejah Royer ◽  
Amy V. Paschall ◽  
Alma Pena-Briseno ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Disease Prevention ◽  
Disease Incidence ◽  
Protein A ◽  
Pneumococcal Infection ◽  
Surface Protein ◽  
Human Monoclonal Antibodies ◽  
Human Mabs ◽  
Prevention And Treatment ◽  
Pneumococcal Serotype

AbstractStreptococcus pneumoniae remains a leading cause of bacterial pneumonia despite the widespread use of vaccines. While vaccines are effective at reducing the incidence of most vaccine-included serotypes, a rise in infection due to non-vaccine serotypes, and moderate efficacy against some vaccine included serotypes have contributed to high disease incidence. Additionally, numerous isolates of S. pneumoniae are antibiotic or multi-drug resistant. Several conserved pneumococcal proteins prevalent in the majority of serotypes have been examined as vaccines in preclinical and clinical trials. An additional, yet unexplored tool for disease prevention and treatment is the use of human monoclonal antibodies (mAbs) targeting conserved pneumococcal proteins. Here, we isolate the first human mAbs (PhtD3, PhtD6, PhtD7, PhtD8, PspA16) against the pneumococcal histidine triad protein (PhtD), and the pneumococcal surface protein A (PspA), two conserved and protective antigens. mAbs to PhtD target diverse epitopes on PhtD, and mAb PspA16 targets the N-terminal segment of PspA. The PhtD-specific mAbs bind to multiple serotypes, while mAb PspA16 serotype breadth is limited. mAbs PhtD3 and PhtD8 prolong the survival of mice infected with pneumococcal serotype 3. Furthermore, mAb PhtD3 prolongs the survival of mice in intranasal and intravenous infection models with pneumococcal serotype 4, and in mice infected with pneumococcal serotype 3 when administered 24 hours after pneumococcal infection. All PhtD and PspA mAbs demonstrate opsonophagocytic activity, suggesting a potential mechanism of protection. Our results provide new human mAbs for pneumococcal disease prevention and treatment, and identify epitopes on PhtD and PspA recognized by human B cells.

scholarly journals Differences in Pneumococcal Serotype Replacement in Individuals with and without Underlying Medical Conditions

2018 ◽  
Author(s):  
Daniel M. Weinberger ◽  
Joshua L Warren ◽  
Tine Dalby ◽  
Eugene D. Shapiro ◽  
Valentiner Branth ◽  
...  
Keyword(s):  
Age Groups ◽  
Risk Groups ◽  
Bayesian Regression ◽  
Childhood Vaccination ◽  
Conjugate Vaccines ◽  
Vaccine Serotypes ◽  
Serotype Replacement ◽  
Pneumococcal Serotype ◽  
Nationwide Surveillance ◽  
The Impact

ABSTRACTBackgroundPneumococcal conjugate vaccines (PCVs) have had a well-documented impact on the incidence of invasive pneumococcal disease (IPD) worldwide. However, declines in IPD due to vaccine-targeted serotypes have been partially offset by increases in IPD due to non-vaccine serotypes. The goal of this study was to quantify serotype-specific changes in the incidence of IPD that occurred in different age groups, with or without certain co-morbidities, following the introduction of PCV7 and PCV13 in the childhood vaccination program in Denmark.MethodsWe used nationwide surveillance data for IPD in Denmark and a hierarchical Bayesian regression framework to estimate changes in the incidence of IPD associated with the introduction of PCV7 (2007) and PCV13 (2010) while controlling for serotype-specific epidemic cycles and unrelated secular trends.Results and ConclusionsFollowing the introduction of PCV7 and 13 in children, the net impact of serotype replacement varied considerably by age group and the presence of comorbid conditions. Serotype replacement offset a greater fraction of the decline in vaccine-targeted serotypes following the introduction of PCV7 compared with the period following the introduction of PCV13. Differences in the magnitude of serotype replacement were due to variations in the incidence of non-vaccine serotypes in the different risk groups before the introduction of PCV7 and PCV13. The relative increases in the incidence of IPD caused by non-vaccine serotypes did not differ appreciably in the post-vaccination period. Serotype replacement offset a greater proportion of the benefit of PCVs in strata in which the non-vaccine serotypes comprised a larger proportion of cases prior to the introduction of the vaccines. These findings could help to predict the impact of next-generation conjugate vaccines in specific risk groups.

scholarly journals Novel Strategy To Protect against Influenza Virus-Induced Pneumococcal Disease without Interfering with Commensal Colonization

2016 ◽  
Vol 84 (6) ◽  
pp. 1693-1703 ◽  
Author(s):  
Christopher J. Greene ◽  
Laura R. Marks ◽  
John C. Hu ◽  
Ryan Reddinger ◽  
Lorrie Mandell ◽  
...  
Keyword(s):  
Influenza A ◽  
Pneumococcal Disease ◽  
Protein A ◽  
Surface Protein ◽  
Attractive Alternative ◽  
Long Term Effects ◽  
Content Type ◽  
Vaccine Type ◽  
Novel Strategy ◽  
Major Surface

Streptococcus pneumoniaecommonly inhabits the nasopharynx as a member of the commensal biofilm. Infection with respiratory viruses, such as influenza A virus, induces commensalS. pneumoniaeto disseminate beyond the nasopharynx and to elicit severe infections of the middle ears, lungs, and blood that are associated with high rates of morbidity and mortality. Current preventive strategies, including the polysaccharide conjugate vaccines, aim to eliminate asymptomatic carriage with vaccine-type pneumococci. However, this has resulted in serotype replacement with, so far, less fit pneumococcal strains, which has changed the nasopharyngeal flora, opening the niche for entry of other virulent pathogens (e.g.,Streptococcus pyogenes,Staphylococcus aureus, and potentiallyHaemophilus influenzae). The long-term effects of these changes are unknown. Here, we present an attractive, alternative preventive approach where we subvert virus-induced pneumococcal disease without interfering with commensal colonization, thus specifically targeting disease-causing organisms. In that regard, pneumococcal surface protein A (PspA), a major surface protein of pneumococci, is a promising vaccine target. Intradermal (i.d.) immunization of mice with recombinant PspA in combination with LT-IIb(T13I), a novel i.d. adjuvant of the type II heat-labile enterotoxin family, elicited strong systemic PspA-specific IgG responses without inducing mucosal anti-PspA IgA responses. This response protected mice from otitis media, pneumonia, and septicemia and averted the cytokine storm associated with septic infection but had no effect on asymptomatic colonization. Our results firmly demonstrated that this immunization strategy against virally induced pneumococcal disease can be conferred without disturbing the desirable preexisting commensal colonization of the nasopharynx.

Association of pneumococcal serotype with susceptibility to antimicrobial drugs: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Kristin Andrejko ◽  
Buddhika Ratnasiri ◽  
Joseph A Lewnard
Keyword(s):  
Systematic Review ◽  
Regression Models ◽  
Meta Analysis ◽  
Invasive Disease ◽  
Epidemiologic Studies ◽  
Antimicrobial Drugs ◽  
Conjugate Vaccines ◽  
Post Vaccination ◽  
Resistance Selection ◽  
Pneumococcal Serotype

Abstract Background Pneumococcal serotypes differ in antimicrobial susceptibility. However, patterns and causes of this variation are not comprehensively understood. Methods We undertook a systematic review of epidemiologic studies of pneumococci isolated from carriage or invasive disease among children globally from 2000-2019. We evaluated associations of each serotype with nonsusceptibility to penicillin, macrolides, and trimethoprim/sulfamethoxazole. We evaluated differences in the prevalence of nonsusceptibility to major antibiotic classes across serotypes using random effects meta-regression models, and assessed changes in prevalence of nonsusceptibility after implementation of pneumococcal conjugate vaccines (PCVs). We also evaluated associations between biological characteristics of serotypes and their likelihood of nonsusceptibility to each drug. Results We included data from 129 studies representing 32,187 isolates across 52 countries. Within serotypes, the proportion of nonsusceptible isolates varied geographically and over time, in settings using and those not using PCVs. Factors predicting enhanced fitness of serotypes in colonization as well as enhanced pathogenicity were each associated with higher likelihood of nonsusceptibility to penicillin, macrolides, and trimethoprim/sulfamethoxazole. Increases in prevalence of nonsusceptibility following PCV implementation were evident among non-PCV serotypes including 6A, 6C, 15A, 15B/C, 19A, and 35B; however, this pattern was not universally evident among non-PCV serotypes. Post-vaccination increases in nonsusceptibility for serotypes 6A and 19A were attenuated in settings that implemented PCV13. Conclusions In pneumococci, nonsusceptibility to penicillin, macrolides, and trimethoprim/sulfamethoxazole is associated with more frequent opportunities for antibiotic exposure during both prolonged carriage episodes and when serotypes cause disease. These findings suggest multiple pathways leading to resistance selection in pneumococci.

scholarly journals Differences in the Impact of Pneumococcal Serotype Replacement in Individuals With and Without Underlying Medical Conditions

2018 ◽  
Vol 69 (1) ◽  
pp. 100-106 ◽  
Author(s):  
Daniel M Weinberger ◽  
Joshua L Warren ◽  
Tine Dalby ◽  
Eugene D Shapiro ◽  
Palle Valentiner-Branth ◽  
...  
Keyword(s):  
Medical Conditions ◽  
Serotype Replacement ◽  
Pneumococcal Serotype ◽  
The Impact

scholarly journals A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against LethalStreptococcus pneumoniaeChallenge

2018 ◽  
Vol 87 (3) ◽  
Author(s):  
Win-Yan Chan ◽  
Claire Entwisle ◽  
Giuseppe Ercoli ◽  
Elise Ramos-Sevillano ◽  
Ann McIlgorm ◽  
...  
Keyword(s):  
Heat Shock ◽  
Protein A ◽  
Surface Protein ◽  
Surface Proteins ◽  
Rabbit Serum ◽  
Protein Antigens ◽  
Content Type ◽  
Multiple Antigen ◽  
Bacterial Lysates ◽  
Chromatography Step

ABSTRACTCurrent vaccination againstStreptococcus pneumoniaeuses vaccines based on capsular polysaccharides from selected serotypes and has led to nonvaccine serotype replacement disease. We have investigated an alternative serotype-independent approach, using multiple-antigen vaccines (MAV) prepared fromS. pneumoniaeTIGR4 lysates enriched for surface proteins by a chromatography step after culture under conditions that induce expression of heat shock proteins (Hsp; thought to be immune adjuvants). Proteomics and immunoblot analyses demonstrated that, compared to standard bacterial lysates, MAV was enriched with Hsps and contained several recognized protective protein antigens, including pneumococcal surface protein A (PspA) and pneumolysin (Ply). Vaccination of rodents with MAV induced robust antibody responses to multiple serotypes, including nonpneumococcal conjugate vaccine serotypes. Homologous and heterologous strains ofS. pneumoniaewere opsonized after incubation in sera from vaccinated rodents. In mouse models, active vaccination with MAV significantly protected against pneumonia, while passive transfer of rabbit serum from MAV-vaccinated rabbits significantly protected against sepsis caused by both homologous and heterologousS. pneumoniaestrains. Direct comparison of MAV preparations made with or without the heat shock step showed no clear differences in protein antigen content and antigenicity, suggesting that the chromatography step rather than Hsp induction improved MAV antigenicity. Overall, these data suggest that the MAV approach may provide serotype-independent protection againstS. pneumoniae.

scholarly journals Pneumococcal Surface Protein A Inhibits Complement Deposition on the Pneumococcal Surface by Competing with the Binding of C-Reactive Protein to Cell-Surface Phosphocholine

2012 ◽  
Vol 189 (11) ◽  
pp. 5327-5335 ◽  
Author(s):  
Reshmi Mukerji ◽  
Shaper Mirza ◽  
Aoife M. Roche ◽  
Rebecca W. Widener ◽  
Christina M. Croney ◽  
...  
Keyword(s):  
Cell Surface ◽  
Protein A ◽  
Surface Protein ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Pneumococcal Surface Protein A ◽  
Complement Deposition
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