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Globalization and Health Jul 2016We analyzed an attempt to develop and clinically test a pneumococcal conjugate vaccine for the developing world, undertaken by public health institutions from the... (Review)
Review
We analyzed an attempt to develop and clinically test a pneumococcal conjugate vaccine for the developing world, undertaken by public health institutions from the Netherlands, Sweden, Denmark, Norway and Finland: the Dutch Nordic Consortium (DNC), between 1990 and 2000. Our review shows that the premature termination of the project was due less to technological and scientific challenges and more to managerial challenges and institutional policies. Various impeding events, financial and managerial challenges gradually soured the initially enthusiastic collaborative spirit until near the end the consortium struggled to complete the minimum objectives of the project. By the end of 1998, a tetravalent prototype vaccine had been made that proved safe and immunogenic in Phase 1 trials in adults and toddlers in Finland. The planned next step, to test the vaccine in Asia in infants, did not meet approval by the local authorities in Vietnam nor later in the Philippines and the project eventually stopped.The Dutch DNC member, the National Institute of Public Health and the Environment (RIVM) learned important lessons, which subsequently were applied in a following vaccine technology transfer project, resulting in the availability at affordable prices for the developing world of a conjugate vaccine against Haemophilus influenzae type b. We conclude that vaccine development in the public domain with technology transfer as its ultimate aim requires major front-end funding, committed leadership at the highest institutional level sustained for many years and a competent recipient-manufacturer, which needs to be involved at a very early stage of the development.At the national level, RIVM's policy to consolidate its national manufacturing task through securing a key global health position in support of a network of public vaccine manufacturers proved insufficiently supported by the relevant ministries of the Dutch government. Difficulties to keep up with high costs, high-risk innovative vaccine development and production in a public sector setting led to the gradual loss of production tasks and to the 2009 Government decision to privatize the vaccine production tasks of the Institute.
Topics: Clinical Trials as Topic; Denmark; Developing Countries; Finland; Humans; Institutional Management Teams; International Cooperation; Netherlands; Norway; Organizational Policy; Pneumococcal Vaccines; Sweden; Technology Transfer; Vaccination
PubMed: 27388678
DOI: 10.1186/s12992-016-0176-6 -
Expert Review of Vaccines Mar 2012In view of the increasing licensure and use of pneumococcal conjugate vaccines, the relatively high cost, and growing issues with serotype emergence, there is a need to... (Review)
Review
In view of the increasing licensure and use of pneumococcal conjugate vaccines, the relatively high cost, and growing issues with serotype emergence, there is a need to re-evaluate the role of pneumococcal protein vaccines (PPVs) and pathways to their licensure. This paper summarizes the discussion and viewpoints from an expert meeting regarding the development of PPVs. A wide spectrum of pneumococcal vaccine researchers, developers, and regulators met to review the state of PPVs, identify research and development needs, and provide consensus opinions to support the introduction of new PPVs where possible. They also discussed clinical and regulatory aspects pertinent to these vaccines and generated a series of recommendations for moving the field forward.
Topics: Animals; Bacterial Proteins; Disease Models, Animal; Humans; Pneumococcal Infections; Pneumococcal Vaccines; Vaccines, Subunit; Virulence Factors
PubMed: 22380821
DOI: 10.1586/erv.12.5 -
Frontiers in Immunology 2021Patients living with HIV (PLHIV) are prone to invasive pneumococcal disease. The 13-valent conjugated pneumococcal vaccine (PCV13) is currently recommended for all...
BACKGROUND
Patients living with HIV (PLHIV) are prone to invasive pneumococcal disease. The 13-valent conjugated pneumococcal vaccine (PCV13) is currently recommended for all PLHIV, followed in most guidelines by a 23-valent polysaccharide pneumococcal vaccine. Data are scarce concerning the immunological efficacy of PCV13 among PLHIV.
OBJECTIVE
To assess the immunological response at one month, and the immunological protection at 1-, 6-, and 12 months in PLHIV with a CD4 cell count above 200 cells/µl after a single dose of PCV13, as measured by both ELISA and opsonophagocytic assay (OPA).
METHODS
PLHIV with CD4 cell count >200 cells/µl were included. Specific IgG serum concentrations for eight serotypes by ELISA and seven serotypes by OPA were measured at baseline, 1-, 6-, and 12 months after the PCV13 vaccination. Global response was defined as a two-fold increase from baseline of specific IgG antibody levels (μg/ml) assayed by ELISA or as a four-fold increase in OPA titer from baseline, for at least five serotypes targeted by PCV13. Global protection was defined as an IgG-concentration ≥1 µg/ml by ELISA or as an opsonization titer ≥LLOQ by OPA for at least five tested serotypes targeted by PCV13. Factors associated with global response and global protection were assessed using logistic regression.
RESULTS
Of the 38 PLHIV included, 57.9% and 63.2% were global responders, 92.1% and 78.9% were globally protected at one month, and 64.7% and 55.9% were still protected at 12 months, by ELISA and OPA respectively. A CD4/CD8 ratio of >0.8 was significantly associated with a better global response by OPA (OR=6.11, p=0.02), and a CD4 nadir <200 was significantly associated with a poorer global response by ELISA (OR=0.22, p=0.04). A CD4 cell count nadir <200 and age over 50 years were associated with poorer global protection by OPA at M1 (OR=0.18, p=0.04) and M12 (OR= 0.15, p=0.02), respectively. Plasma HIV RNA viral load <40 copies/ml was significantly associated with a better global protection at M1 by ELISA and OPA (OR=21.33, p=0.025 and OR=8.40, p=0.04).
CONCLUSION
Vaccination with PCV13 in these patients induced immunological response and protection at one month. At one year, more than half of patients were still immunologically protected.
Topics: Adult; Antibodies, Bacterial; Biological Assay; Biomarkers; CD4 Lymphocyte Count; Enzyme-Linked Immunosorbent Assay; Female; France; HIV Infections; HIV Long-Term Survivors; HL-60 Cells; Humans; Immunocompromised Host; Immunogenicity, Vaccine; Male; Middle Aged; Opsonization; Pneumococcal Infections; Pneumococcal Vaccines; Prospective Studies; Time Factors; Treatment Outcome; Vaccination; Vaccine Efficacy
PubMed: 34987514
DOI: 10.3389/fimmu.2021.791147 -
Human Vaccines & Immunotherapeutics 2016All currently available Streptococcus pneumoniae (Spn) vaccines have limitations due to their capsular serotype composition. Both the 23-valent Spn polysaccharide... (Review)
Review
All currently available Streptococcus pneumoniae (Spn) vaccines have limitations due to their capsular serotype composition. Both the 23-valent Spn polysaccharide vaccine (PPV) and 7, 10, or 13-valent Spn conjugate vaccines (PCV-7, 10, -13) are serotype-based vaccines and therefore they elicit only serotype-specific immunity. Emergence of replacement Spn strains expressing other serotypes has consistently occurred following introduction of capsular serotype based Spn vaccines. Furthermore, capsular polysaccharide vaccines are less effective in protection against non-bacteremic pneumonia and acute otitis media (AOM) than against invasive pneumococcal disease (IPD). These shortcomings of capsular polysaccharide-based Spn vaccines have created high interest in development of non-serotype specific protein-based vaccines that could be effective in preventing both IPD and non-IPD infections. This review discusses the progress to date on development of Spn protein vaccine candidates that are highly conserved by all Spn strains, are highly conserved, exhibit maximal antigenicity and minimal reactogenicity to replace or complement the current capsule-based vaccines. Key to development of a protein based Spn vaccine is an understanding of Spn pathogenesis. Based on pathogenesis, a protein-based Spn vaccine should include one or more ingredients that reduce NP colonization below a pathogenic inoculum. Elimination of all Spn colonization may not be achievable or even advisable. The level of expression of a target protein antigen during pathogenesis is another key to the success of protein based vaccines.. As with virtually all currently licensed vaccines, production of a serum antibody response in response to protein based vaccines is anticipated to provide protection from Spn infections. A significant advantage that protein vaccine formulations can offer over capsule based vaccination is their potential benefits associated with natural priming and boosting to all strains of Spn. One of the most universal and comprehensive approaches of identifying novel vaccine candidates is the investigation of human sera from different disease stages of natural infections. Antigens that are robustly reactive in preliminary human serum screening constitute a pathogen-specific antigenome. This strategy has identified a number of Spn protein vaccine candidates that are moving forward in human clinical trials.
Topics: Animals; Antigens, Bacterial; Bacterial Proteins; Clinical Trials as Topic; Drug Discovery; Drug Evaluation, Preclinical; Humans; Pneumococcal Vaccines; Streptococcus pneumoniae
PubMed: 26539741
DOI: 10.1080/21645515.2015.1052198 -
Frontiers in Immunology 2022VSA-1 is a semisynthetic saponin adjuvant prepared from naturally occurring saponin and capable of stimulating antigen-specific humoral and cellular immune responses....
VSA-1 is a semisynthetic saponin adjuvant prepared from naturally occurring saponin and capable of stimulating antigen-specific humoral and cellular immune responses. Its immunostimulating activity in enhancing the immune responses induced by the clinical glycoconjugate pneumococcal vaccine PCV13 is compared with QS-21 in female BALB/c mice. Both VSA-1 and QS-21 boosted IgG and opsonic antibodies titers against seven selected serotypes, including serotypes 3, 14, and 19A that are involved in most PCV13 breakthroughs. Since VSA-1 is much more accessible and of lower toxicity than QS-21, it can be a practical saponin immunostimulant to be included in a new glycoconjugate pneumococcal vaccine formulation.
Topics: Animals; Mice; Female; Pneumococcal Vaccines; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Immunoglobulin G; Saponins
PubMed: 36578488
DOI: 10.3389/fimmu.2022.1079047 -
The Netherlands Journal of Medicine Oct 2008The burden of community-acquired pneumonia (CAP) among the elderly is high and has increased over the last decades. Streptococcus pneumoniae is the most common cause of... (Review)
Review
The burden of community-acquired pneumonia (CAP) among the elderly is high and has increased over the last decades. Streptococcus pneumoniae is the most common cause of CAP and in 10% the infection may be fatal. Although the 23-valent polysaccharide pneumococcal vaccine (23vPS) is considered effective in the prevention of invasive pneumococcal disease in the elderly population, the evidence is mainly from nonrandomised observational studies and effects on the occurrence of pneumonia have not been demonstrated. Conjugated pneumococcal vaccines which also stimulate T-cell dependent immune responses induced antibody responses in elderly persons which are similar to those induced by a primary series of 7-valent conjugated pneumococcal vaccine (7vPnC) in infants, and the response appeared similar or superior for all vaccine serotypes to that induced by 23vPS. The primary objective of the planned trial entitled CAPITA (Community Acquired Pneumonia Immunization Trial in Adults) is to establish the efficacy of a 13-valent PnC vaccine in the prevention of a first episode of vaccine-serotype specific pneumococcal CAP in 85,000 community-dwelling adult persons aged 65 years and older. This is a parallel group, randomised, placebo-controlled trial, with a 1:1 random allocation to vaccine or placebo vaccine. The occurrence of the primary outcome of vaccine-serotype specific (VT)-CAP will be established in hospitals on the basis of three sets of criteria: (1) a clinical definition of CAP; (2) independent interpretation of chest radiograph consistent with pneumonia: and (3) determination of S. pneumonia serotype. the trial will be critical to determine the position of conjugate pneumococcal vaccines in the prevention of pneumococcal disease.
Topics: Aged; Humans; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Randomized Controlled Trials as Topic; Streptococcus pneumoniae; Treatment Outcome
PubMed: 18990781
DOI: No ID Found -
Frontiers in Immunology 2021In every year, up to one million children die due to pneumococcal disease. Children infected with Human Immunodeficiency Virus (HIV) are mostly affected, as they appear... (Randomized Controlled Trial)
Randomized Controlled Trial
Immunogenicity and Efficacy of Pneumococcal Conjugate Vaccine (Prevenar13) in Preventing Acquisition of Carriage of Pneumococcal Vaccine Serotypes in Tanzanian Children With HIV/AIDS.
UNLABELLED
In every year, up to one million children die due to pneumococcal disease. Children infected with Human Immunodeficiency Virus (HIV) are mostly affected, as they appear to have higher rates of pneumococcal carriage and invasive disease. Successful immunity is dependent on mounting a sufficient immune response to the vaccine. We conducted a double blinded crossover randomised controlled trial to determine the serum antibody response (≥4-fold and geometric mean concentration) to pneumococcal vaccine (PCV13) serotypes at 3 months after second vaccination. We also determined the number and proportion of children carrying new (not present at baseline) vaccine serotypes of isolated from nasopharynx at 6 months post initial vaccination in recipients of Prevenar13 compared with those given -type b (Hib) vaccine (control). The study was conducted at St Augustine's also known as Teule Hospital in Muheza, Tanga Tanzania. 225 HIV infected children aged 1-14 years were enrolled from Jan 2013 to Nov 2013 and randomised to Prevenar13 or Hib vaccines each given at baseline and 2-3 months later. Nasopharyngeal and serum samples were collected at baseline and 4-6 months later. Serotyping was done by Quellung Reaction using Staten antisera. Serum antibodies were ELISA quantified. The study revealed a non-significant reduction in the acquisition of new vaccine serotypes of in the recipients of PCV13 by nearly a third compared to those who received Hib vaccine. The vaccine efficacy was 30.5% (95% confidence interval [CI] -6.4-54.6%, P = 0.100)]. The antibody response was not enough to induce a 4-fold rise in GMC in 7 of the 13 vaccine serotypes. When combining the effects of preventing new acquisition and clearing existing vaccine type carriage, the overall efficacy was 31.5% (95% CI 1.5-52.4%, P = 0.045). In the PCV13 group, the proportion of participants carrying vaccine serotype was significantly lower after 2 doses of PCV13 (30%; 32/107), compared with the baseline proportion (48%; 51/107). The introduction of PCV13 targeting HIV-positive children in a setting similar to Tanzania is likely to be associated with appreciable decrease in the acquisition and carriage of pneumococci, which is an important marker of the likely effect of the vaccine on pneumococcal disease.
CLINICAL TRIAL REGISTRATION
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=335579, identifier ACTRN12610000999033.
Topics: Acquired Immunodeficiency Syndrome; Adolescent; Antibodies, Bacterial; Carrier State; Child; Child, Preschool; Cross-Over Studies; Double-Blind Method; Female; HIV Infections; Humans; Infant; Male; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Streptococcus pneumoniae; Tanzania; Vaccines, Conjugate
PubMed: 34220819
DOI: 10.3389/fimmu.2021.673392 -
Value in Health Regional Issues Dec 2016To assess the efficacy, cost-effectiveness, immunogenicity, and safety related to the interchangeability between pneumococcal conjugate vaccines (PCVs) and vaccination... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To assess the efficacy, cost-effectiveness, immunogenicity, and safety related to the interchangeability between pneumococcal conjugate vaccines (PCVs) and vaccination schedules in pediatric population.
METHODS
Systematic searches were conducted in December 2010 and April 2015 for economic evaluations in MEDLINE, EMBASE, LILACS, and Cochrane Central Register of Controlled Trials. Web sites and databases from medical societies, experts, and associations related to the topic, proceedings or congressional annals, and doctoral theses were also searched. No language or temporal restriction was applied. We included randomized controlled trials, economic evaluations, and systematic reviews evaluating antibody response, cost-effectiveness, and effectiveness of PCVs' interchangeability. A Strengthening the Reporting of Observational Studies in Epidemiology-based checklist was used to assess the risk of bias in observational studies and a Cochrane approach for experimental/quasi-experimental studies. Pairs of reviewers independently selected (through the Web-based Early Reviewer Organizer Software), assessed the quality, and extracted the data of the studies. Discrepancies were resolved by consensus. We planned to perform meta-analysis whenever appropriate.
RESULTS
Forty-six of 202 studies were included. There was no direct information available on the interchangeability between PCVs. The immunogenicity and safety between the 10-valent PCV (PCV10) and the 7-valent PCV were similar when both vaccines were coadministered with other routine pediatric vaccines. PCV10 and 13-valent PCV (PCV13) were consistently more cost-effective than 7-valent PCV.
CONCLUSIONS
There was no direct comparative information available on the interchangeability among PCVs, but they have pretty similar immunogenicity and safety. PCV10 versus PCV13 cost-effectiveness varied according to price, indirect effects, and indirect costs. PCV10 gains more quality-adjusted life-years because of the prevention of more frequent yet less severe events such as otitis media, and PCV13 prevents less frequent but more costly events such as invasive diseases.
Topics: Child; Cost-Benefit Analysis; Humans; Otitis Media; Pneumococcal Infections; Pneumococcal Vaccines; Vaccination; Vaccines, Conjugate
PubMed: 27986195
DOI: 10.1016/j.vhri.2015.12.001 -
In Vivo (Athens, Greece) 2019Streptococcus pneumoniae is the leading cause of bacterial pneumonia and an important cause of invasive disease. Despite the antiretroviral therapies, adults infected... (Review)
Review
BACKGROUND/AIM
Streptococcus pneumoniae is the leading cause of bacterial pneumonia and an important cause of invasive disease. Despite the antiretroviral therapies, adults infected with human immunodeficiency virus (HIV) are at particular risk for invasive pneumococcal disease (IPD). The purpose of this study was to report the efficacy of the strategies currently being used in pneumococcal vaccination for HIV-infected adults.
MATERIALS AND METHODS
A literature search was performed through electronic databases, for original articles in English, from years 2000 to 2019. Clinical trials controlled or randomized, and cohort studies were included.
RESULTS
While 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for immunocompromised patients, it has been reported that it is less suitable for HIV-infected patients. Recent guidelines have added pneumococcal conjugate vaccine (PCV) to the list of recommended vaccines.
CONCLUSION
Further studies are needed to determine the optimal vaccines and intervals for subsequent revaccinations during the lifetime.
Topics: HIV Infections; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Immunocompromised Host; Pneumococcal Infections; Pneumococcal Vaccines; Vaccination
PubMed: 31471388
DOI: 10.21873/invivo.11620 -
Atencion Primaria Sep 2002Estimate pneumococcal vaccine effectiveness in preventing Streptococcus pneumoniae illness in the elderly. (Comparative Study)
Comparative Study Meta-Analysis Review
AIM
Estimate pneumococcal vaccine effectiveness in preventing Streptococcus pneumoniae illness in the elderly.
DESIGN
Systematic review and meta-analysis. DATA SOURCE. MEDLINE, years 1964 to the 2000; EMBASE, from 1988 to the 2000; Cochrane Library, identified studies and previously published systematic reviews citations peruse, and contacts with field experts.
STUDY SELECTION
Clinical trials, cohort and case-control studies, published in Spanish, English or French, that estimated pneumococcal disease rates in vaccinated or not vaccinated elderly.
DATA EXTRACTION
The studies were valued independently by four investigators with predefined criteria of validity, such as results comparing rates of disease caused by serotypes included in the vaccine, random allocation, double blind design, included subjects pertaining to the same study base, and losses of less than 10% in clinical trials and 20% in observational studies.
RESULTS
Eight clinical trials considered the relative risk (RR) of pneumococcal pneumonia, three did not make estimations on pneumonia originated by serotypes included in the vaccine and only one study fulfilled all the inclusion criteria. Vaccinated versus not vaccinated pneumococcal pneumonia RR was 0.86 (95%CI, 0.24 to 2.99). Vaccine effectiveness was 14% (95%CI, -199 to 76%). Ten studies performed estimations on the effectiveness of the vaccine on invasive disease by vaccine serotypes. Of these, two clinical trials and two observational studies fulfilled the required quality criteria. RR of invasive disease was of 0.68 (95%CI, 0.39-1.18); vaccine effectiveness was 32% (95%CI, 18-61%).
CONCLUSIONS
No evidence was found supporting pneumococcal vaccine effectiveness to reduce or avoid S. pneumoniae disease in the elderly.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Case-Control Studies; Clinical Trials as Topic; Cohort Studies; Double-Blind Method; Humans; Middle Aged; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Random Allocation; Risk
PubMed: 12372207
DOI: 10.1016/s0212-6567(02)79027-6