Development of Pneumococcal Vaccines for the World

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Vaccines and Therapeutic Developments".

Deadline for manuscript submissions: closed (15 August 2021) | Viewed by 22025

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Science and Engineering Department, University College Roosevelt, 4331 CB Middelburg, The Netherlands
Interests: immunology; immunodeficiency; vaccination; pneumococcal pneumonia; SARS-CoV-2
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Dear Colleagues,

Ninety years ago, Oswald Avery made a breakthrough discovery when he coupled proteins to bacterial polysaccharides and found that the resulting conjugate possessed improved immunogenicity and even induced immunological memory. After a lag period of over half a century, his principles have been applied in the design of a whole new category of pneumococcal vaccines: The pneumococcal conjugate vaccines. These vaccines, directed against the 7–13 most prevalent pneumococcal serotypes, are effective in the prevention of both invasive as well as mucosal pneumococcal infections in children. Despite this success, and despite antibiotic treatment options, the burden of pneumococcal pneumonia in terms of morbidity and mortality remains high, both for children and the elderly. The issues to be addressed in the field of vaccine development are serotype coverage, serotype replacement, geographical distribution of serotypes, nature of the vaccines (polysaccharide or protein based), as well as (economical) affordability. We therefore invite all clinical and biomedical researchers, whether from this field or coming from a clinical, public health, or manufacturing background, to submit their work to be considered for publication in this Special Issue.

Prof. Dr. Ger Rijkers
Guest Editor

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Keywords

  • pneumococcal vaccines
  • polysaccharide conjugates
  • global epidemiology
  • pneumonia
  • pediatric
  • elderly

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Published Papers (5 papers)

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Research

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9 pages, 530 KiB  
Article
Characteristics of Serotype 3 Invasive Pneumococcal Disease before and after Universal Childhood Immunization with PCV13 in Massachusetts
by Rotem Lapidot, Kimberly M. Shea, Inci Yildirim, Howard J. Cabral, Stephen I. Pelton and the Massachusetts Department of Public Health
Pathogens 2020, 9(5), 396; https://doi.org/10.3390/pathogens9050396 - 21 May 2020
Cited by 27 | Viewed by 3661
Abstract
Background: Although a substantial decline in vaccine-serotype invasive pneumococcal disease (IPD) incidence was observed following the introduction of pneumococcal conjugate vaccines (PCV), the estimated range of thirteen-valent conjugate vaccine (PCV13) effectiveness for serotype 3 disease is wide and includes zero. We assessed the [...] Read more.
Background: Although a substantial decline in vaccine-serotype invasive pneumococcal disease (IPD) incidence was observed following the introduction of pneumococcal conjugate vaccines (PCV), the estimated range of thirteen-valent conjugate vaccine (PCV13) effectiveness for serotype 3 disease is wide and includes zero. We assessed the impact of PCV13 on serotype 3 IPD incidence and disease characteristics in Massachusetts’ children. Methods: Serotype 3 IPD cases in children <18 years old were identified via enhanced passive surveillance system in Massachusetts. We compared incidence rates and characteristics of IPD cases before and after PCV13. Results: A total of 47 serotype 3 IPD cases were identified from 2002 to 2017; incidence of serotype 3 IPD in the years following PCV13 was 0.19 per 100,000 children compared to 0.21 before PCV 13, incidence rate ratio (IRR) = 0.86 (95% CI 0.47–1.57). The majority (78%) of post-PCV13 serotype 3 IPD cases occurred among fully vaccinated children. Age distribution, clinical syndrome and presence of comorbidities among serotype 3 IPD cases were similar before and after PCV13 introduction. There was no association between the date of the last PCV13 dose and time to IPD to suggest waning of immunity. Conclusions: seven years following PCV 13 we found no significant changes in serotype 3 IPD incidence or disease characteristics in children in Massachusetts. Full article
(This article belongs to the Special Issue Development of Pneumococcal Vaccines for the World)
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16 pages, 1818 KiB  
Article
Streptococcus pneumoniae Nasopharyngeal Carriage among PCV-10-Vaccinated HIV-1-Infected Children with Maintained Serological Memory in Ethiopia
by Mahlet Lemma, Yonas Bekele, Stefan Petkov, Moa Hägglund, Beyene Petros, Abraham Aseffa, Rawleigh Howe and Francesca Chiodi
Pathogens 2020, 9(3), 159; https://doi.org/10.3390/pathogens9030159 - 25 Feb 2020
Cited by 1 | Viewed by 4407
Abstract
Streptococcus pneumoniae (S. pneumoniae) vaccines have substantially reduced the burden of invasive pneumococcal diseases (IPDs) worldwide. Despite high coverage with S. pneumoniae vaccination, upper-respiratory-tract colonization by S. pneumoniae is still common. We assessed maintenance of serological responses to S. pneumoniae serotypes [...] Read more.
Streptococcus pneumoniae (S. pneumoniae) vaccines have substantially reduced the burden of invasive pneumococcal diseases (IPDs) worldwide. Despite high coverage with S. pneumoniae vaccination, upper-respiratory-tract colonization by S. pneumoniae is still common. We assessed maintenance of serological responses to S. pneumoniae serotypes included in PCV-10 by ELISA in HIV-1-infected children (n = 50) and age-matched controls (n = 50) in Ethiopia. We isolated S. pneumoniae in nasopharyngeal swabs and determined S. pneumoniae serotype by whole genome sequencing (WGS). Comparable levels of S. pneumoniae serotype-specific IgG concentrations were detected in plasma of HIV-1-infected children and matched controls, with geometric mean concentrations (GMCs) consistently higher than the protective threshold for PCV-10 serotypes of 0.35 μg/mL. We isolated S. pneumoniae from 38 (out of 97) nasopharyngeal swabs, 25 from HIV-1-infected children and 13 from controls. WGS based serotyping revealed 22 known S. pneumoniae serotypes and 2 nontypeable (NT) isolates. Non-PCV-10 serotypes represented >90% of isolates. We showed that HIV-1-infected children and matched controls in Ethiopia carry a level of maintained serological memory to PCV-10 considered protective for IPDs. We identified a higher proportion of nasopharyngeal carriage with highly pathogenic S. pneumoniae non-PCV strains among HIV-1-infected children compared to controls. Full article
(This article belongs to the Special Issue Development of Pneumococcal Vaccines for the World)
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16 pages, 995 KiB  
Article
Estimating the Clinical and Economic Impact of Switching from the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) to the 10-Valent Pneumococcal Conjugate Vaccine (PCV10) in Italy
by Filippo Ansaldi, Sarah Pugh, Daniela Amicizia, Roberto Di Virgilio, Cecilia Trucchi, Andrea Orsi, Alessandro Zollo and Giancarlo Icardi
Pathogens 2020, 9(2), 76; https://doi.org/10.3390/pathogens9020076 - 22 Jan 2020
Cited by 16 | Viewed by 4082
Abstract
Background: Invasive and non-invasive pneumococcal diseases are significant health and economic burdens, especially in children and the elderly. Italy included the 7-valent (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) in the National Immunization Program in 2007 and 2010, respectively, allowing a dramatic [...] Read more.
Background: Invasive and non-invasive pneumococcal diseases are significant health and economic burdens, especially in children and the elderly. Italy included the 7-valent (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) in the National Immunization Program in 2007 and 2010, respectively, allowing a dramatic reduction in the burden of pneumococcal disease. In the era of budget constraints, decision-makers may consider switching from the higher-valent, more costly PCV13, to the lower-cost PCV10. This study estimated the potential public health and economic impact of changing vaccine programs from PCV13 to PCV10 in Italy. Methods: A decision-analytic forecasting model estimated the impact of PCV programs. Real-world surveillance data were used to forecast serotype distribution and disease incidence among children and the elderly over a specified 5-year time horizon. Costs and outcomes included estimates of cases and deaths avoided, quality-adjusted life years (QALYs) gained, and total costs from a payer perspective, discounted at an assumed rate of 3.0%, and robustness validated through several scenarios and sensitivity analyses. Results: A switch from PCV13 to PCV10 would increase invasive pneumococcal disease (IPD) cases by 59.3% (4317 cases) over a 5-year horizon, primarily due to serotypes 3 and 19A. Pneumonia increased by 8.3% and acute otitis media (AOM) by 96.1%. Maintaining a PCV13 program would prevent a total incremental 531,435 disease cases (1.02M over a 10-year time horizon) and 641 deaths due to invasive pneumococcal disease (IPD), with €23,642 per QALY gained over 5 years versus PCV10. One-way and probabilistic sensitivity analyses showed that a PCV13-based program remained cost-effective in 99.7% of the simulations in Italy as parameters varied within their plausible range; percent vaccinated had the most impact. Conclusions: Maintaining the PCV13 strategy would provide substantial public health and economic benefits in Italy and is cost-effective. Switching from PCV13 to PCV10 would increase the incidence of pneumococcal disease primarily linked to re-emergence of serotypes 3 and 19A. Full article
(This article belongs to the Special Issue Development of Pneumococcal Vaccines for the World)
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Review

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15 pages, 1281 KiB  
Review
A Systematic Review of Studies Published between 2016 and 2019 on the Effectiveness and Efficacy of Pneumococcal Vaccination on Pneumonia and Invasive Pneumococcal Disease in an Elderly Population
by Jacob Dag Berild, Brita Askeland Winje, Didrik Frimann Vestrheim, Hans-Christian Slotved, Palle Valentiner-Branth, Adam Roth and Jann Storsäter
Pathogens 2020, 9(4), 259; https://doi.org/10.3390/pathogens9040259 - 3 Apr 2020
Cited by 33 | Viewed by 6196
Abstract
Adult vaccination is high on the agenda in many countries. Two different vaccines are available for the prevention of pneumococcal disease in adults: a 23-valent polysaccharide vaccine (PPV23), and a 13-valent conjugated vaccine (PCV13). The objective of this review is to update the [...] Read more.
Adult vaccination is high on the agenda in many countries. Two different vaccines are available for the prevention of pneumococcal disease in adults: a 23-valent polysaccharide vaccine (PPV23), and a 13-valent conjugated vaccine (PCV13). The objective of this review is to update the evidence base for vaccine efficacy and effectiveness of PPV23 and PCV13 against invasive pneumococcal disease and pneumonia among an unselected elderly population. We systematically searched for clinical trials and observational studies published between January 1 2016 and April 17 2019 in Pubmed, Embase, Cinahl, Web of Science, Epistemonikos and Cochrane databases. Risk of bias was assessed using Cochrane Risk of Bias tool for and the Newcastle–Ottawa Scale. Results were stratified by vaccine type and outcome. We identified nine studies on PCV13 and six on PPV23. No new randomized clinical trials were identified. Due to different outcomes, it was not possible to do a meta-analysis. New high-quality observational studies indicate protective vaccine effectiveness for both vaccines against vaccine type pneumonia. Our estimates for the protective vaccine efficacy and effectiveness (VE) of PPV23 on pneumonia and pneumococcal pneumonia overlap with results from previously published reviews. Some of the results indicate that the effectiveness of the PPV23 is best in younger age groups, and that it decreases over time. Full article
(This article belongs to the Special Issue Development of Pneumococcal Vaccines for the World)
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Other

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11 pages, 272 KiB  
Perspective
Opening the OPK Assay Gatekeeper: Harnessing Multi-Modal Protection by Pneumococcal Vaccines
by Ashleigh N. Riegler, Beth Mann, Carlos J. Orihuela and Elaine Tuomanen
Pathogens 2019, 8(4), 203; https://doi.org/10.3390/pathogens8040203 - 23 Oct 2019
Cited by 1 | Viewed by 2787
Abstract
Pneumococcal vaccine development is driven by the achievement of high activity in a single gatekeeper assay: the bacterial opsonophagocytic killing (OPK) assay. New evidence challenges the dogma that anti-capsular antibodies have only a single function that predicts success. The emerging concept of multi-modal [...] Read more.
Pneumococcal vaccine development is driven by the achievement of high activity in a single gatekeeper assay: the bacterial opsonophagocytic killing (OPK) assay. New evidence challenges the dogma that anti-capsular antibodies have only a single function that predicts success. The emerging concept of multi-modal protection presents an array of questions that are fundamental to adopting a new vaccine design process. If antibodies have hidden non-opsonic functions that are protective, should these be optimized for better vaccines? What would protein antigens add to protective activity? Are cellular immune functions additive to antibodies for success? Do different organs benefit from different modes of protection? Can vaccine activities beyond OPK protect the immunocompromised host? This commentary raises these issues at a time when capsule-only OPK assay-based vaccines are increasingly seen as a limiting strategy. Full article
(This article belongs to the Special Issue Development of Pneumococcal Vaccines for the World)
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