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Frontiers in Public Health 2023This study aims to assess the economic impact of introducing the 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine... (Comparative Study)
Comparative Study
INTRODUCTION
This study aims to assess the economic impact of introducing the 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) to Thai older adult aged ≥ 65 years who are healthy or with chronic health conditions and immunocompromised conditions from a societal perspective in order to introduce the vaccine to Thailand's National Immunization Program for the older adult.
METHODS
A Markov model was adopted to simulate the natural history and economic outcomes of invasive pneumococcal diseases using updated published sources and Thai databases. We reported analyses as incremental cost-effectiveness ratios (ICER) in USD per quality-adjusted life year (QALY) gained. In addition, sensitivity analyses and budget impact analyses were conducted.
RESULTS
The base-case analysis of all interventions (no vaccinations [current standard of care in Thailand], PPSV23, and PCV13) showed that PPSV23 was extendedly dominated by PCV13. Among healthy individuals or those with chronic health conditions, ICER for PCV13 was 233.63 USD/QALY; meanwhile, among individuals with immunocompromised conditions, ICER for PCV13 was 627.24 USD/QALY. PCV13 are economical vaccine for all older adult Thai individuals when compared to all interventions.
CONCLUSIONS
In the context of Thailand, PCV13 is recommended as the best buy and should be primarily prioritized when both costs and benefits are considered. Also, this model will be beneficial to the two-next generation pneumococcal vaccines implementation in Thailand.
Topics: Aged; Humans; Cost-Benefit Analysis; Cost-Effectiveness Analysis; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Southeast Asian People; Thailand; Vaccines, Conjugate
PubMed: 37457251
DOI: 10.3389/fpubh.2023.1071117 -
Indian Journal of Medical Microbiology 2019India is one among the four Asian countries with the greatest number of deaths due to pneumococcal infection among children under 5 years. pneumococcal conjugate vaccine...
India is one among the four Asian countries with the greatest number of deaths due to pneumococcal infection among children under 5 years. pneumococcal conjugate vaccine (PCV) has been introduced in a phased manner in five major Indian states. Ambiguity remains in choosing the appropriate type of PCV and optimum schedule with maximum effectiveness specific for each country. Here, we discuss the evidences with respect to serotype coverage, immunogenicity, reactogenicity and dosage schedule for introduction of PCV13 in India. In addition, the expected PCV impact and the challenges are detailed. PCV13 is expected to provide >75% serotype coverage for invasive pneumococcal disease (IPD) serotypes in Indian children combined with the replacement by nonvaccine serotypes which is unpredictable due to lack of complete data. Nasopharyngeal (NP) surveillance is easy, feasible and can replace IPD surveillance in resource-poor settings. Continuous IPD as well as NP surveillance in all the regions are necessary to assess the impact of PCV in India.
Topics: Age Factors; Female; Health Impact Assessment; Humans; Immunization Programs; Immunization Schedule; India; Male; Outcome Assessment, Health Care; Pneumococcal Infections; Pneumococcal Vaccines; Public Health Surveillance; Serogroup; Streptococcus pneumoniae; Vaccines, Conjugate
PubMed: 31745013
DOI: 10.4103/ijmm.IJMM_19_320 -
The Lancet. Microbe Sep 2023The effect of childhood pneumococcal conjugate vaccine implementation in Malawi is threatened by absence of herd effect. There is persistent vaccine-type pneumococcal... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of 13-valent pneumococcal conjugate vaccine on experimental carriage of Streptococcus pneumoniae serotype 6B in Blantyre, Malawi: a randomised controlled trial and controlled human infection study.
BACKGROUND
The effect of childhood pneumococcal conjugate vaccine implementation in Malawi is threatened by absence of herd effect. There is persistent vaccine-type pneumococcal carriage in both vaccinated children and the wider community. We aimed to use a human infection study to measure 13-valent pneumococcal conjugate vaccine (PCV13) efficacy against pneumococcal carriage.
METHODS
We did a double-blind, parallel-arm, randomised controlled trial investigating the efficacy of PCV13 or placebo against experimental pneumococcal carriage of Streptococcus pneumoniae serotype 6B (strain BHN418) among healthy adults (aged 18-40 years) from Blantyre, Malawi. We randomly assigned participants (1:1) to receive PCV13 or placebo. PCV13 and placebo doses were prepared by an unmasked pharmacist to maintain research team and participant masking with identification only by a randomisation identification number and barcode. 4 weeks after receiving either PCV13 or placebo, participants were challenged with 20 000 colony forming units (CFUs) per naris, 80 000 CFUs per naris, or 160 000 CFUs per naris by intranasal inoculation. The primary endpoint was experimental pneumococcal carriage, established by culture of nasal wash at 2, 7, and 14 days. Vaccine efficacy was estimated per protocol by means of a log-binomial model adjusting for inoculation dose. The trial is registered with the Pan African Clinical Trials Registry, PACTR202008503507113, and is now closed.
FINDINGS
Recruitment commenced on April 27, 2021 and the final visit was completed on Sept 12, 2022. 204 participants completed the study protocol (98 PCV13, 106 placebo). There were lower carriage rates in the vaccine group at all three inoculation doses (0 of 21 vs two [11%] of 19 at 20 000 CFUs per naris; six [18%] of 33 vs 12 [29%] of 41 at 80 000 CFUs per naris, and four [9%] of 44 vs 16 [35%] of 46 at 160 000 CFUs per naris). The overall carriage rate was lower in the vaccine group compared with the placebo group (ten [10%] of 98 vs 30 [28%] of 106; Fisher's p value=0·0013) and the vaccine efficacy against carriage was estimated at 62·4% (95% CI 27·7-80·4). There were no severe adverse events related to vaccination or inoculation of pneumococci.
INTERPRETATION
This is, to our knowledge, the first human challenge study to test the efficacy of a pneumococcal vaccine against pneumococcal carriage in Africa, which can now be used to establish vaccine-induced correlates of protection and compare alternative strategies to prevent pneumococcal carriage. This powerful tool could lead to new means to enhance reduction in pneumococcal carriage after vaccination.
FUNDING
Wellcome Trust.
Topics: Adult; Child; Humans; Malawi; Streptococcus pneumoniae; Vaccines, Conjugate; Serogroup; Pneumococcal Vaccines
PubMed: 37659418
DOI: 10.1016/S2666-5247(23)00178-7 -
Expert Review of Vaccines Dec 2017Epidemiologic evaluations of Streptococcus pneumoniae nasopharyngeal (NP) colonization and pneumococcal disease suggest that newer serotypes in future formulations of... (Review)
Review
Epidemiologic evaluations of Streptococcus pneumoniae nasopharyngeal (NP) colonization and pneumococcal disease suggest that newer serotypes in future formulations of pneumococcal conjugate vaccines (PCVs) are needed and there may need to be continued reformulations because there are many new emerging serotypes expressed by pneumococci. Areas covered: Mechanisms of protection by next-generation whole-cell vaccine (WCV) and/or multi-component pneumococcal purified protein vaccines (PPVs) in development for prevention of pneumococcal infections. Expert commentary: A long-term strategy for prevention of pneumococcal disease will likely include WCV and PPVs. However these vaccines will impact disease pathogenesis in a different manner than PCVs. Prevention of pneumococcal NP colonization should not be expected, nor is it desirable because risks for NP colonization by other replacement organisms into the ecological niche vacated by all pneumococci may have consequences. The expression biology of capsule and surface protein antigens are phase dependent. Therefore, the immune response will be different and the mechanism of protection divergent. WCVs and PPVs may be alternative strategies in low income developing countries to protect against invasive disease and reduce NP carriage load.
Topics: Drug Discovery; Humans; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; Vaccines, Inactivated; Vaccines, Subunit
PubMed: 29130395
DOI: 10.1080/14760584.2017.1393335 -
Journal of Immunological Methods Oct 2018Quantitative assays that measure immune response to pneumococcal vaccines are not only important for the evaluation of vaccine immunogenicity and efficacy, but are also... (Review)
Review
Quantitative assays that measure immune response to pneumococcal vaccines are not only important for the evaluation of vaccine immunogenicity and efficacy, but are also utilized in the clinical diagnosis of immune deficiency syndromes. Analytical methods have progressed in order to meet changing demands in both of these areas, from early methods to ELISA, and most recently multiplex bead array assays and opsonophagocytosis assays (OPA). It is necessary to understand the evolution of such techniques and the criteria for their interpretation in order to better inform the application of currently available methods, and to guide future investigation into assay development.
Topics: Adaptive Immunity; Antibodies, Bacterial; Enzyme-Linked Immunosorbent Assay; Humans; Immunologic Deficiency Syndromes; Pneumococcal Vaccines
PubMed: 30098317
DOI: 10.1016/j.jim.2018.08.002 -
Molecular Pharmaceutics Apr 2021We previously developed a safe and effective nasal vaccine delivery system using a self-assembled nanosized hydrogel (nanogel) made from a cationic cholesteryl pullulan....
We previously developed a safe and effective nasal vaccine delivery system using a self-assembled nanosized hydrogel (nanogel) made from a cationic cholesteryl pullulan. Here, we generated three pneumococcal surface protein A (PspA) fusion antigens as a universal pneumococcal nasal vaccine and then encapsulated each PspA into a nanogel and mixed the three resulting monovalent formulations into a trivalent nanogel-PspA formulation. First, to characterize the nanogel-PspA formulations, we used native polyacrylamide gel electrophoresis (PAGE) to determine the average number of PspA molecules encapsulated per nanogel molecule. Second, we adopted two methods-a densitometric method based on lithium dodecyl sulfate (LDS)-PAGE and a biologic method involving sandwich enzyme-linked immunosorbent assay (ELISA)-to determine the PspA content in the nanogel formulations. Third, treatment of nanogel-PspA formulations by adding methyl-β-cyclodextrin released each PspA in its native form, as confirmed through circular dichroism (CD) spectroscopy. However, when nanogel-PspA formulations were heat-treated at 80 °C for 16 h, CD spectroscopy showed that each PspA was released in a denatured form. Fourth, we confirmed that the nanogel-PspA formulations were internalized into nasal mucosa effectively and that each PspA was gradually released from the nanogel in epithelial cells in mice. Fifth, LDS-PAGE densitometry and ELISA both indicated that the amount of trivalent PspA was dramatically decreased in the heat-treated nanogel compared with that before heating. When mice were immunized nasally using the heat-treated formulation, the immunologic activity of each PspA was dramatically reduced compared with that of the untreated formulation; in both cases, the immunologic activity correlated well with the content of each PspA as determined by LDS-PAGE densitometry and ELISA. Finally, we confirmed that the trivalent nanogel-PspA formulation induced equivalent titers of PspA-specific serum IgG and mucosal IgA Abs in immunized mice. These results show that the specification methods we developed effectively characterized our nanogel-based trivalent PspA nasal vaccine formulation.
Topics: Administration, Intranasal; Animals; Bacterial Proteins; Drug Liberation; Female; Glucans; Humans; Hygroscopic Agents; Immunogenicity, Vaccine; Mice; Models, Animal; Nanogels; Nasal Mucosa; Pneumococcal Infections; Pneumococcal Vaccines; Recombinant Fusion Proteins; Streptococcus pneumoniae; beta-Cyclodextrins
PubMed: 33621107
DOI: 10.1021/acs.molpharmaceut.0c01003 -
BMC Infectious Diseases Oct 2015Pneumococcal diseases remain a leading cause of vaccine-preventable death worldwide in children <5 years of age. The seven-valent pneumococcal conjugate vaccine (PCV7)... (Review)
Review
BACKGROUND
Pneumococcal diseases remain a leading cause of vaccine-preventable death worldwide in children <5 years of age. The seven-valent pneumococcal conjugate vaccine (PCV7) was approved in 2001 in Europe and was introduced into the national immunization programmes of many European countries from 2006-2008. In 2009, higher-valent PCVs (PCV10 and PCV13) became available, replacing PCV7 from 2009-2011. This article describes the evolution of vaccine and non-vaccine serotypes causing invasive pneumococcal disease (IPD) following the introduction of PCVs in Western Europe, based on data from publicly-available medical publications and national surveillance systems from January 2010 to May 2015.
DISCUSSION
In countries with high vaccine uptake, 5-7 years after PCV7 introduction IPD caused by vaccine serotypes has almost disappeared in children. Non-PCV7 serotypes have emerged, particularly serotypes 19A, 7 F, 3 and 1. A rapid and significant reduction of the additional serotypes included in higher-valent vaccines has been observed consistently following the introduction of these vaccines. A significant and rapid decline of serotypes 19A, 7 F, 1 and 6A in both vaccine-eligible and older age groups has been observed in countries using PCV13 while serotype 19A and 3 has increased in countries using PCV10. Serotype 3 has become one of the most prevalent serotypes in adults, with some reduction only in the UK and France. Serotype diversity increased and varied by age group, the type of vaccine in use, and the time since the introduction of higher-valent PCVs. Serotypes that are currently more frequent include 24 F, 22 F, 8 and 15A in countries that use PCV13, and serotypes 19A and 3 in countries that use PCV10. Compared with the time before the introduction of higher valent PCVs, to date, there is no single '19A-like' serotype emerging across countries and most of the newly emerging non-PCV13 vaccine types are less invasive with a low case-carrier ratio.
CONCLUSIONS
It is important to closely monitor not only evolving serotypes but also the magnitude of the effect in order to evaluate the overall impact of pneumococcal vaccination programmes and to initiate the appropriate vaccination strategy. Emerging serotypes may also need to be considered for the future development of new vaccines.
Topics: Adolescent; Aged; Child; Child, Preschool; Europe; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Immunization Programs; Infant; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Serotyping; Streptococcus pneumoniae; Vaccines, Conjugate
PubMed: 26468008
DOI: 10.1186/s12879-015-1147-x -
Clinical Microbiology and Infection :... Oct 2013Streptococcus pneumoniae-related infections are a major cause of morbidity and mortality in people of all ages worldwide. Pneumococcal vaccine development started in... (Review)
Review
Streptococcus pneumoniae-related infections are a major cause of morbidity and mortality in people of all ages worldwide. Pneumococcal vaccine development started in 1911 with a whole cell vaccine and more recently multivalent plain polysaccharide and polysaccharide conjugate vaccines have been developed. The recent vaccines rely on capsular polysaccharide antigens to induce serotype-specific immune responses. We summarize here the presentations on pneumococcal polysaccharide conjugate vaccine (conjugated to CRM197 carrier protein) given during the integrated symposium organized and funded by Pfizer International Operations during the 22nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 31 March to 3 April 2012, London, UK. A dramatic reduction in the incidence of invasive pneumococcal diseases (IPD) due to vaccine serotypes (VST-IPD) has been reported since the introduction of a hepta-valent pneumococcal conjugate vaccine (PCV7). An indirect (herd) effect has been demonstrated to be associated with PCV7 infant vaccination programmes, with many studies reporting reductions in VST-IPD in populations that are not eligible for PCV7 vaccination. Since 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) has been introduced into national immunization programmes and results from early surveillance suggest that this vaccine also has an impact on the serotypes unique to PCV13, as well as continuing to protect against the PCV7 serotypes. Data from a passive surveillance system in Europe in 2009, for instance, showed that the highest incidence of IPD remains in those aged >65 years and in children <5 years. PCV13 has now been licensed for vaccination of adults >50 years based on safety and immunogenicity data; an efficacy trial is being conducted. Regardless of previous pneumococcal vaccination status, if the use of 23-valent polysaccharide is considered appropriate, it is recommended to give PCV13 first. Novel immunization strategies remain the only practical means to reduce significantly the remaining global mortality and morbidity due to S. pneumoniae in adults.
Topics: Adult; Bacterial Proteins; Child; Europe; Humans; Immunization Programs; Pneumococcal Infections; Pneumococcal Vaccines; Polysaccharides, Bacterial; Population Surveillance; Streptococcus pneumoniae; Vaccination; Vaccines, Conjugate
PubMed: 24083785
DOI: 10.1111/1469-0691.12320 -
Annals of the American Thoracic Society Jun 2016Streptococcus pneumoniae is an important global pathogen that causes a wide range of clinical disease in children and adults. Pneumococcal pneumonia is by far the common... (Review)
Review
Streptococcus pneumoniae is an important global pathogen that causes a wide range of clinical disease in children and adults. Pneumococcal pneumonia is by far the common presentation of noninvasive and invasive pneumococcal disease and affects the young, the elderly, and the immunocompromised disproportionately. Patients with chronic pulmonary diseases are also at higher risk for pneumococcal infections. Substantial progress over the century has been made in the understanding of pneumococcal immunobiology and the prevention of invasive pneumococcal disease through vaccination. Currently, two pneumococcal vaccines are available for individuals at risk of pneumococcal disease: the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent pneumococcal protein-conjugate vaccine (PCV13). The goal of pneumococcal vaccination is to stimulate effective antipneumococcal antibody and mucosal immunity response and immunological memory. Vaccination of infants and young children with pneumococcal conjugate vaccine has led to significant decrease in nasal carriage rates and pneumococcal disease in all age groups. Recent pneumococcal vaccine indication and schedule recommendations on the basis of age and risk factors are outlined in this Focused Review. As new pneumococcal vaccine recommendations are being followed, continued efforts are needed to address the vaccine efficacy in the waning immunity of the ever-aging population, the implementation of vaccines using two different vaccines under very specific schedules and their real world clinical and cost effectiveness, and the development of next generation pneumococcal vaccines.
Topics: Cost-Benefit Analysis; Humans; Immunity, Herd; Immunization Schedule; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Randomized Controlled Trials as Topic; Risk Factors; Streptococcus pneumoniae; Vaccines, Conjugate
PubMed: 27088424
DOI: 10.1513/AnnalsATS.201511-778FR -
PLoS Pathogens Dec 2017Colonization of the human nasopharynx by pneumococcus is extremely common and is both the primary reservoir for transmission and a prerequisite for disease. Current... (Review)
Review
Colonization of the human nasopharynx by pneumococcus is extremely common and is both the primary reservoir for transmission and a prerequisite for disease. Current vaccines targeting the polysaccharide capsule effectively prevent colonization, conferring herd protection within vaccinated communities. However, these vaccines cover only a subset of all circulating pneumococcal strains, and serotype replacement has been observed. Given the success of pneumococcal conjugate vaccine (PCV) in preventing colonization in unvaccinated adults within vaccinated communities, reducing nasopharyngeal colonization has become an outcome of interest for novel vaccines. Here, we discuss the immunological mechanisms that control nasopharyngeal colonization, with an emphasis on findings from human studies. Increased understanding of these immunological mechanisms is required to identify correlates of protection against colonization that will facilitate the early testing and design of novel vaccines.
Topics: Carrier State; Humans; Nasopharynx; Pneumococcal Infections; Pneumococcal Vaccines; Vaccines, Conjugate
PubMed: 29267378
DOI: 10.1371/journal.ppat.1006665