Editorial

3 pages, 134 KiB

Open AccessEditorial

Pneumococcal Vaccines: Challenges and Prospects

by Paul Licciardi and Ioanna Papadatou

Vaccines 2019, 7(1), 25; https://doi.org/10.3390/vaccines7010025 - 27 Feb 2019

Cited by 3 | Viewed by 2950

Infections with the bacterium Streptococcus pneumoniae are one of the most common causes of morbidity and mortality in children less than five years of age worldwide, mostly in low- and middle-income countries (LMICs) [...] Full article

(This article belongs to the Special Issue Vaccines for Pneumococcal Infections)

Research

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14 pages, 2002 KiB

Open AccessArticle

Immunogenicity and Immune Memory after a Pneumococcal Polysaccharide Vaccine Booster in a High-Risk Population Primed with 10-Valent or 13-Valent Pneumococcal Conjugate Vaccine: A Randomized Controlled Trial in Papua New Guinean Children

by Anita H. J. van den Biggelaar, William S. Pomat, Geraldine Masiria, Sandra Wana, Birunu Nivio, Jacinta Francis, Rebecca Ford, Megan Passey, Lea-Ann Kirkham, Peter Jacoby, Deborah Lehmann, Peter Richmond and the 10v13v PCV Trial Team

Vaccines 2019, 7(1), 17; https://doi.org/10.3390/vaccines7010017 - 04 Feb 2019

Cited by 5 | Viewed by 3823

Abstract

We investigated the immunogenicity, seroprotection rates and persistence of immune memory in young children at high risk of pneumococcal disease in Papua New Guinea (PNG). Children were primed with 10-valent (PCV10) or 13-valent pneumococcal conjugate vaccines (PCV13) at 1, 2 and 3 months [...] Read more.

We investigated the immunogenicity, seroprotection rates and persistence of immune memory in young children at high risk of pneumococcal disease in Papua New Guinea (PNG). Children were primed with 10-valent (PCV10) or 13-valent pneumococcal conjugate vaccines (PCV13) at 1, 2 and 3 months of age and randomized at 9 months to receive PPV (PCV10/PPV-vaccinated, n = 51; PCV13/PPV-vaccinated, n = 52) or no PPV (PCV10/PPV-naive, n = 57; PCV13/PPV-naive, n = 48). All children received a micro-dose of PPV at 23 months of age to study the capacity to respond to a pneumococcal challenge. PPV vaccination resulted in significantly increased IgG responses (1.4 to 10.5-fold change) at 10 months of age for all PPV-serotypes tested. Both PPV-vaccinated and PPV-naive children responded to the 23-month challenge and post-challenge seroprotection rates (IgG ≥ 0.35 μg/mL) were similar in the two groups (80–100% for 12 of 14 tested vaccine serotypes). These findings show that PPV is immunogenic in 9-month-old children at high risk of pneumococcal infections and does not affect the capacity to produce protective immune responses. Priming with currently available PCVs followed by a PPV booster in later infancy could offer improved protection to young children at high risk of severe pneumococcal infections caused by a broad range of serotypes. Full article

(This article belongs to the Special Issue Vaccines for Pneumococcal Infections)

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14 pages, 1581 KiB

Open AccessArticle

PCV7- and PCV10-Vaccinated Otitis-Prone Children in New Zealand Have Similar Pneumococcal and Haemophilus influenzae Densities in Their Nasopharynx and Middle Ear

by Camilla de Gier, Caitlyn M. Granland, Janessa L. Pickering, Tony Walls, Mejbah Bhuiyan, Nikki Mills, Peter C. Richmond, Emma J. Best, Ruth B. Thornton and Lea-Ann S. Kirkham

Vaccines 2019, 7(1), 14; https://doi.org/10.3390/vaccines7010014 - 31 Jan 2019

Cited by 11 | Viewed by 4001

Abstract

Otitis media (OM) is a major reason for antibiotic consumption and surgery in children. Nasopharyngeal carriage of otopathogens, Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi), is a prerequisite for development of OM, and increased nasopharyngeal otopathogen density correlates with disease onset. Vaccines can [...] Read more.

Otitis media (OM) is a major reason for antibiotic consumption and surgery in children. Nasopharyngeal carriage of otopathogens, Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi), is a prerequisite for development of OM, and increased nasopharyngeal otopathogen density correlates with disease onset. Vaccines can reduce or eliminate otopathogen carriage, as demonstrated for pneumococcal serotypes included in pneumococcal conjugate vaccines (PCV). The 10-valent PCV (PCV10) includes an NTHi carrier protein, and in 2011 superseded 7-valent PCV on the New Zealand Immunisation Program. Data are conflicting on whether PCV10 provides protection against NTHi carriage or disease. Assessing this in otitis-prone cohorts is important for OM prevention. We compared otopathogen density in the nasopharynx and middle ear of New Zealand PCV7-vaccinated and PCV10-vaccinated otitis-prone and non-otitis-prone children to determine PCV10 impact on NTHi and S. pneumoniae carriage. We applied qPCR to specimens collected from 217 PCV7-vaccinated children (147 otitis-prone and 70 non-otitis-prone) and 240 PCV10-vaccinated children (178 otitis-prone and 62 non-otitis-prone). After correcting for age and day-care attendance, no difference was observed between NTHi density in the nasopharynx of PCV7-vaccinated versus PCV10-vaccinated otitis-prone (p = 0.563) or non-otitis-prone (p = 0.513) children. In contrast, pneumococcal nasopharyngeal density was higher in PCV10-vaccinated otitis-prone children than PCV7-vaccinated otitis-prone children (p = 0.003). There was no difference in otopathogen density in middle ear effusion from PCV7-vaccinated versus PCV10-vaccinated otitis-prone children (NTHi p = 0.918; S. pneumoniae p = 0.415). When pneumococcal carriage was assessed by vaccine serotypes (VT) and non-vaccine serotypes (NVT), there was no difference in VT density (p = 0.546) or NVT density (p = 0.315) between all PCV7-vaccinated versus all PCV10-vaccinated children. In summary, PCV10 did not reduce NTHi density in the nasopharynx or middle ear, and was associated with increased pneumococcal nasopharyngeal density in otitis-prone children in New Zealand. Development of therapies that prevent or reduce otopathogen colonisation density in the nasopharynx are warranted to reduce the burden of OM. Full article

(This article belongs to the Special Issue Vaccines for Pneumococcal Infections)

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10 pages, 909 KiB

Open AccessCommunication

Should Pneumococcal Serotype 3 Be Included in Serotype-Specific Immunoassays?

by Ezra Linley, Abigail Bell, Jenna F. Gritzfeld and Ray Borrow

Vaccines 2019, 7(1), 4; https://doi.org/10.3390/vaccines7010004 - 03 Jan 2019

Cited by 29 | Viewed by 4130

Abstract

Since the introduction of the 13-valent pneumococcal conjugate vaccine, a number of studies have demonstrated the limited efficacy of the pneumococcal serotype 3 component of this vaccine. Evidence from seven countries (Denmark, France, Greece, Portugal, Sweden, UK, US) shows limited or no effectiveness [...] Read more.

Since the introduction of the 13-valent pneumococcal conjugate vaccine, a number of studies have demonstrated the limited efficacy of the pneumococcal serotype 3 component of this vaccine. Evidence from seven countries (Denmark, France, Greece, Portugal, Sweden, UK, US) shows limited or no effectiveness of the 13-valent pneumococcal conjugate vaccine against serotype 3 invasive pneumococcal disease and carriage. The serotype 3 capsule has some unique characteristics that may serve to explain this lack of efficacy—capsular polysaccharide is abundantly expressed, leading to a greater thickness of capsule, and free capsular polysaccharide may be released during growth. The serotype 3 component of the Luminex multiplex assay demonstrates inferior inter-laboratory reproducibility than other components and results may not be reliable. This communication outlines this evidence and discusses whether it is necessary to include serotype 3 in the assay in the future. Full article

(This article belongs to the Special Issue Vaccines for Pneumococcal Infections)

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10 pages, 903 KiB

Open AccessArticle

Serotype-Specific IgG Antibody Waning after Pneumococcal Conjugate Primary Series Vaccinations with either the 10-Valent or the 13-Valent Vaccine

by Els Van Westen, Mirjam J. Knol, Alienke J. Wijmenga-Monsuur, Irina Tcherniaeva, Leo M. Schouls, Elisabeth A. M. Sanders, Cecile A. C. M. Van Els, Guy A. M. Berbers and Nynke Y. Rots

Vaccines 2018, 6(4), 82; https://doi.org/10.3390/vaccines6040082 - 11 Dec 2018

Cited by 13 | Viewed by 3929

Abstract

The two currently available ten- and thirteen-valent pneumococcal conjugate vaccines (PCV10 and PCV13) both induce serotype-specific IgG anti-polysaccharide antibodies and are effective in preventing vaccine serotype induced invasive pneumococcal disease (IPD) as well as in reducing overall vaccine-serotype carriage and transmission and thereby [...] Read more.

The two currently available ten- and thirteen-valent pneumococcal conjugate vaccines (PCV10 and PCV13) both induce serotype-specific IgG anti-polysaccharide antibodies and are effective in preventing vaccine serotype induced invasive pneumococcal disease (IPD) as well as in reducing overall vaccine-serotype carriage and transmission and thereby inducing herd protection in the whole population. IgG levels decline after vaccination and could become too low to prevent carriage acquisition and/or pneumococcal disease. We compared the levels of 10-valent (PCV10) and 13-valent (PCV13) pneumococcal vaccine induced serum IgG antibodies at multiple time points after primary vaccinations. Data from two separate studies both performed in the Netherlands in infants vaccinated at 2, 3, and 4 months of age with either PCV10 or PCV13 were compared. Antibody levels were measured at 5, 8, and 11 months of age, during the interval between the primary immunization series and the 11-months booster dose. Serotype-specific IgG levels were determined by multiplex immunoassay. Although antibody kinetics showed significant variation between serotypes and between vaccines for the majority of the 10 shared serotypes, i.e., 1, 5, 7F, 9V, 14, 18C, and 23F, antibody concentrations were sufficiently high for both vaccines, immediately after the primary series and throughout the whole period until the booster dose. In contrast, for serotypes 4 and 19F in the PCV10 group and for serotypes 4 and 6B in the PCV13 group, IgG antibody concentrations already come within reach of the frequently used seroprotection level of 0.35 μg/mL immediately after the primary series at the five month time point and/or at eight months. This paper addresses the importance of revealing differences in serotype-specific and pneumococcal vaccine-dependent IgG antibody patterns during the interval between the primary series and the booster dose, an age period with a high IPD incidence. Trial registration: www.trialregister.nl NTR3069 and NTR2316. Full article

(This article belongs to the Special Issue Vaccines for Pneumococcal Infections)

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12 pages, 1531 KiB

Open AccessArticle

Relative Clinical and Cost Burden of Community-Acquired Pneumonia Hospitalizations in Older Adults in the United States—A Cross-Sectional Analysis

by Omotola Olasupo, Hong Xiao and Joshua D. Brown

Vaccines 2018, 6(3), 59; https://doi.org/10.3390/vaccines6030059 - 31 Aug 2018

Cited by 31 | Viewed by 4264

Abstract

The relative burden of community-acquired pneumonia (CAP) in older adults (≥65 years old) compared to other serious diseases is important to prioritize preventive treatment. A retrospective analysis was conducted using the 2014 National Readmission Database to evaluate the length of stay, inpatient mortality, [...] Read more.

The relative burden of community-acquired pneumonia (CAP) in older adults (≥65 years old) compared to other serious diseases is important to prioritize preventive treatment. A retrospective analysis was conducted using the 2014 National Readmission Database to evaluate the length of stay, inpatient mortality, 30-day readmissions, and costs of CAP compared to diabetes mellitus (DM), myocardial infarction (MI), and stroke. 275,790 hospitalizations were analyzed and represented a national estimate of 616,300 hospitalizations, including 269,961 for CAP, 71,284 for DM, 126,946 for MI, and 148,109 for stroke. The mean length of stay in CAP was 5.2 days, which was higher than DM (4.6) and MI (4.3) but similar to stroke (5.6). The inpatient mortality risk was lower for DM (RR: 0.37, 95% CI: 0.29–0.46) but higher for MI (RR: 1.67, 95% CI: 1.50–1.85) and stroke (RR: 1.67, 95% CI: 1.51–1.83). The median costs for CAP ($7282) were higher compared to DM ($6217) but lower compared to MI ($14,802) and stroke ($8772). The 30-day readmission rate was 17% in CAP, which was higher compared to MI (15%) and stroke (11.5%) and lower compared to DM (20.3%). In patients with CAP, disease burden is on par with other serious diseases. CAP should be prioritized for prevention in older adults with strategies such as vaccination and smoking cessation. Full article

(This article belongs to the Special Issue Vaccines for Pneumococcal Infections)

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Review

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15 pages, 1330 KiB

Open AccessReview

The Role of Serotype-Specific Immunological Memory in Pneumococcal Vaccination: Current Knowledge and Future Prospects

by Ioanna Papadatou, Irene Tzovara and Paul V. Licciardi

Vaccines 2019, 7(1), 13; https://doi.org/10.3390/vaccines7010013 - 29 Jan 2019

Cited by 25 | Viewed by 7129

Abstract

Streptococcus pneumoniae (S. pneumoniae, pneumococcus) is a major cause of morbidity and mortality worldwide. Achieving long-term immunity against S. pneumoniae through immunization is an important public health priority. Long-term protection after immunization is thought to rely both on protective serum antibody [...] Read more.

Streptococcus pneumoniae (S. pneumoniae, pneumococcus) is a major cause of morbidity and mortality worldwide. Achieving long-term immunity against S. pneumoniae through immunization is an important public health priority. Long-term protection after immunization is thought to rely both on protective serum antibody levels and immunological memory in the form of antigen-specific memory B cells (MBCs). Although the ability to achieve protective antibody levels shortly after pneumococcal vaccination has been well documented for the various infant immunization schedules currently in use worldwide, the examination of immunological memory in the form of antigen-specific MBCs has been much more limited. Such responses are critical for long-term protection against pneumococcal colonization and disease. This review summarizes the published literature on the MBC response to primary or booster immunization with either pneumococcal polysaccharide vaccine (PPV23) or pneumococcal conjugate vaccines (PCVs), aiming to elucidate the immunological mechanisms that determine the magnitude and longevity of vaccine protection against pneumococcus. There is evidence that PCVs induce the production of antigen-specific MBCs, whereas immunization with PPV23 does not result in the formation of MBCs. Increased understanding of the immunological factors that facilitate the induction, maintenance and recall of MBCs in response to pneumococcal vaccination could enable the use of MBC enumeration as novel correlates of protection against S. pneumoniae. Ongoing studies that examine MBC response to pneumococcal vaccination in high burden settings will be extremely important in our understanding of long-term protection induced by pneumococcal conjugate vaccines. Full article

(This article belongs to the Special Issue Vaccines for Pneumococcal Infections)

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18 pages, 3525 KiB

Open AccessReview

Novel Protein-Based Pneumococcal Vaccines: Assessing the Use of Distinct Protein Fragments Instead of Full-Length Proteins as Vaccine Antigens

by Theano Lagousi, Paraskevi Basdeki, John Routsias and Vana Spoulou

Vaccines 2019, 7(1), 9; https://doi.org/10.3390/vaccines7010009 - 19 Jan 2019

Cited by 46 | Viewed by 5021

Abstract

Non-serotype-specific protein-based pneumococcal vaccines have received extensive research focus due to the limitations of polysaccharide-based vaccines. Pneumococcal proteins (PnPs), universally expressed among serotypes, may induce broader immune responses, stimulating humoral and cellular immunity, while being easier to manufacture and less expensive. Such an [...] Read more.

Non-serotype-specific protein-based pneumococcal vaccines have received extensive research focus due to the limitations of polysaccharide-based vaccines. Pneumococcal proteins (PnPs), universally expressed among serotypes, may induce broader immune responses, stimulating humoral and cellular immunity, while being easier to manufacture and less expensive. Such an approach has raised issues mainly associated with sequence/level of expression variability, chemical instability, as well as possible undesirable reactogenicity and autoimmune properties. A step forward employs the identification of highly-conserved antigenic regions within PnPs with the potential to retain the benefits of protein antigens. Besides, their low-cost and stable construction facilitates the combination of several antigenic regions or peptides that may impair different stages of pneumococcal disease offering even wider serotype coverage and more efficient protection. This review discusses the up-to-date progress on PnPs that are currently under clinical evaluation and the challenges for their licensure. Focus is given on the progress on the identification of antigenic regions/peptides within PnPs and their evaluation as vaccine candidates, accessing their potential to overcome the issues associated with full-length protein antigens. Particular mention is given of the use of newer delivery system technologies including conjugation to Toll-like receptors (TLRs) and reformulation into nanoparticles to enhance the poor immunogenicity of such antigens. Full article

(This article belongs to the Special Issue Vaccines for Pneumococcal Infections)

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