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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 -
Interdisciplinary Topics in Gerontology... 2020Determining the optimal vaccination strategy for the protection of the elderly population against pneumococcal disease remains a challenge. Older adults are, second to... (Review)
Review
Determining the optimal vaccination strategy for the protection of the elderly population against pneumococcal disease remains a challenge. Older adults are, second to young infants, most susceptible to become colonized and invaded by Streptococcus pneumoniae, causing serious disease such as bacteremic pneumonia, sepsis, and meningitis. In an era with increasing antimicrobial resistance and the growing susceptible population of aged adults, S. pneumoniae is a priority bacterial pathogen for research and development of new intervention strategies. While elderly indirectly profit from infant immunization programs through herd immunity, vaccination of older age groups can offer more direct protection. Two types of pneumococcal vaccines for adults, both based on capsular polysaccharide serotypes, are currently available but have limitations, such as short-lived protection or limited serotype coverage. These vaccine limitations and the biological aging of the immune system call for novel vaccination strategies for the older adults. Here, we highlight how host-pathogen interactions, immune protection, and effectiveness of currently available vaccines shift with increasing age, and how future pneumococcal vaccine strategies could be tailored for the elderly.
Topics: Aged; Humans; Immunity, Herd; Immunization Programs; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Streptococcus pneumoniae; Vaccination; Vaccines, Conjugate
PubMed: 32294656
DOI: 10.1159/000504490 -
Jornal de Pediatria 2023To describe the impact of the 10-valent pneumococcal conjugate vaccine on the pediatric burden of pneumococcal infections, carriage, serotype replacement, and... (Review)
Review
OBJECTIVE
To describe the impact of the 10-valent pneumococcal conjugate vaccine on the pediatric burden of pneumococcal infections, carriage, serotype replacement, and antimicrobial resistance in Brazil since its introduction in 2010.
DATA SOURCE
A narrative review of English, Spanish, and Portuguese articles published in online databases and in Brazilian epidemiological surveillance databases was performed. The following keywords were used: Streptococcus pneumoniae, pneumococcal disease, conjugate vaccine, PCV10, antimicrobial resistance, and meningitis.
SUMMARY OF THE FINDINGS
Declines in hospitalization rates of all-cause pneumonia occurred in the target age groups and some age groups not targeted by vaccination early after the use of PCV10. Large descriptive studies of laboratory-confirmed pneumococcal meningitis and hospital-based historical series of hospitalized children with IPD have evidenced a significant impact on disease burden, in-hospital fatality rates, and admission to the intensive care unit before and after the inclusion of the vaccine. Impact data on otitis media is limited and inconsistent; the main benefit remains the prevention of complicated diseases. During the late post-vaccine years, a significant and progressive increase in high-level penicillin non-susceptibility pneumococci has been described. Since 2014 serotype 19A has been the leading serotype in all ages and was responsible for 28.2%-44.6% of all IPD in children under 5 yrs.
CONCLUSIONS
PCV10 has performed a significant impact on IPD in Brazil since 2010, however, progress has been continuously hampered by replacement. Broader spectrum PCVs could provide expanded direct and indirect protection against ST19A and other additional serotypes of increasing importance if administered to children in the Brazilian National Immunization Program.
Topics: Child; Humans; Infant; Streptococcus pneumoniae; Brazil; Pneumococcal Infections; Pneumococcal Vaccines; Anti-Infective Agents; Vaccines, Conjugate
PubMed: 36495946
DOI: 10.1016/j.jped.2022.11.003 -
Aging Clinical and Experimental Research May 2023Older adults and immunocompromised individulas are often excluded from vaccine trials. (Review)
Review
BACKGROUND
Older adults and immunocompromised individulas are often excluded from vaccine trials.
AIM
We hypothesised that during the coronavirus disease 2019 (COVID-19) pandemic, the proportion of trials excluding these patients decreased.
METHODS
Using the US Food and Drug Administration and and European Medicines Agency search engines, we identified all vaccines approved against pneumococcal disease, influenza (quadrivalent vaccines), and COVID-19 from 2011 to 2021. Study protocols were screened for direct and indirect age exclusion criteria and exclusion of immunocompromised individuals. In addition, we reviewed the studies with no explicit exclusion criteria and investigated the actual inclusion of those individuals.
RESULTS
We identified 2024 trial records; 1702 were excluded (e.g., use of other vaccine or risk group); and 322 studies were eligible for our review. Among the pneumococcal and influenza vaccine trials (n = 193), 81 (42%) had an explicit direct age exclusion, and 150 (78%) had an indirect age-related exclusion. In total, 163 trials (84%) trials were likely to exclude older adults. Among the COVID-19 vaccine trials (n = 129), 33 (26%) had direct age exclusion and 82 (64%) had indirect age exclusion; in total, 85 (66%) trials were likely to exclude older adults. Therefore was a 18% decrease in the proportion of trials with age-related exclusion between 2011 and 2021 (only influenza and pneumococcal vaccine trials) and 2020-2021 (only COVID-19 vaccine trials) (p = 0.014). In a sub-analysis assessing observational and randomised trials, the decrease was 25% and 9%, respectively. Immunocompromised individuals were included in 87 (45%) of the pneumococcal and influenza vaccine trials compared with 54 (42%) of the COVID-19 vaccine trials (p = 0.058).
CONCLUSIONS
During the COVID-19 pandemic, we found a decrease in the exclusion of older adults from vaccine trials but no significant change in the inclusion of immunocompromised individulas.
Topics: Humans; Aged; Influenza, Human; Influenza Vaccines; COVID-19 Vaccines; Pandemics; COVID-19; Pneumococcal Vaccines
PubMed: 37027085
DOI: 10.1007/s40520-023-02380-4 -
Expert Review of Vaccines Jan 2020: Serotype replacement - a consequence of polysaccharide vaccine use - will continue to drive the inclusion of new serotypes on conjugate vaccines, increasing production... (Review)
Review
: Serotype replacement - a consequence of polysaccharide vaccine use - will continue to drive the inclusion of new serotypes on conjugate vaccines, increasing production complexity and costs, and making an already expensive vaccine less accessible to developing countries, where prevalence is higher and resources available for health systems, scarcer. Serotype-independent formulations are a promising option, but so far they have not been successful in reducing colonization/transmission.: Protein-based and whole-cell vaccine candidates studied in the past 30 years. Challenges for serotype-independent vaccine development and alternative approaches.: Clinical trials performed so far demonstrated the importance to establish more reliable animal models and better correlates of protection. Defining appropriate endpoints for clinical trials of serotype-independent vaccine candidates has been a challenge. Inhibition of colonization has been evaluated, but concern on the extent of bacterial elimination is still a matter of debate. Challenges on establishing representative sites for clinical trials, sample sizes and appropriate age groups are discussed. On a whole, although many challenges will have to be overcome, establishing protein-based antigens as serotype-independent vaccines is still the best alternative against the huge burden of pneumococcal diseases in the world.
Topics: Animals; Antigens, Bacterial; Bacterial Proteins; Humans; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Vaccines, Conjugate
PubMed: 31903805
DOI: 10.1080/14760584.2020.1711055 -
Vaccine Apr 2024Pneumococcal conjugate vaccines (PCVs) significantly reduced pneumococcal disease burden. Nevertheless, alternative approaches for controlling more serotypes are needed.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Pneumococcal conjugate vaccines (PCVs) significantly reduced pneumococcal disease burden. Nevertheless, alternative approaches for controlling more serotypes are needed. Here, the safety, tolerability, and immunogenicity of a 24-valent (1/2/3/4/5/6A/6B/7F/8/9N/9V/10A/11A/12F/14/15B/17F/18C/19A/19F/20B/22F/23F/33F) pneumococcal vaccine based on Multiple Antigen-Presenting System (MAPS) technology (Pn-MAPS24v) was assessed in toddlers.
METHODS
In this phase 1, blinded, dose-escalation, active-controlled multicenter study conducted in the United States (September/2020-April/2022), 12-15-month-old toddlers primed with three doses of 13-valent PCV (PCV13) were randomized 3:2 to receive a single dose of one of three Pn-MAPS24v dose levels (1 μg/2 μg/5 μg per polysaccharide) or PCV13 intramuscularly. Reactogenicity (within 7 days), treatment-emergent adverse events (TEAEs, within 180 days), serious/medically attended adverse events (SAEs/MAAEs, within 180 days), and immunogenicity (serotype-specific anti-capsular polysaccharide immunoglobulin G [IgG] and opsonophagocytic activity [OPA] responses at 30 days post-vaccination) were assessed.
RESULTS
Of 75 toddlers enrolled, 74 completed the study (Pn-MAPS24v 1 μg/2 μg/5 μg: 15/14/16, PCV13: 29). Frequencies of local (60 %/67 %/31 %) and systemic events (67 %/67 %/75 %) in the Pn-MAPS24v 1 μg/2 μg/5 μg and the PCV13 (55 %, 79 %) groups were in similar ranges. TEAEs were reported by 47 %/40 %/63 % of Pn-MAPS24v 1 μg/2 μg/5 μg recipients and 52 % of PCV13 recipients. No vaccine-related SAE was reported. At 30 days post-vaccination, for each of the 13 common serotypes, ≥93 % of participants in each group had IgG concentrations ≥0.35 μg/mL; >92 % had OPA titers ≥lower limit of quantitation (LLOQ), except for serotype 1 (79 %). For 7/11 unique serotypes (2/8/9N/11A/17F/22F/33F), at all dose levels, ≥78 % of Pn-MAPS24v recipients in each group had IgG concentrations ≥0.35 μg/mL and 80 %-100 % had OPA titers ≥LLOQ.
CONCLUSIONS
In 12-15-month-old toddlers, a single dose of Pn-MAPS24v showed an acceptable safety profile, regardless of dose level; AEs were reported at similar frequencies by Pn-MAPS24v and PCV13 recipients. Pn-MAPS24v elicited IgG and OPA responses to all common and most unique serotypes. These results support further clinical evaluation in infants.
Topics: Humans; Infant; Antibodies, Bacterial; Immunogenicity, Vaccine; Immunoglobulin G; Pneumococcal Infections; Pneumococcal Vaccines; Polysaccharides; Streptococcus pneumoniae; Vaccines, Conjugate
PubMed: 38360475
DOI: 10.1016/j.vaccine.2024.02.001 -
Pneumococcal Phasevarions Control Multiple Virulence Traits, Including Vaccine Candidate Expression.Microbiology Spectrum Jun 2022Streptococcus pneumoniae is the most common cause of bacterial illness worldwide. Current vaccines based on the polysaccharide capsule are only effective against a...
Streptococcus pneumoniae is the most common cause of bacterial illness worldwide. Current vaccines based on the polysaccharide capsule are only effective against a limited number of the >100 capsular serotypes. A universal vaccine based on conserved protein antigens requires a thorough understanding of gene expression in S. pneumoniae. All S. pneumoniae strains encode the SpnIII Restriction-Modification system. This system contains a phase-variable methyltransferase that switches specificity, and controls expression of multiple genes-a phasevarion. We examined the role of this phasevarion during pneumococcal pathobiology, and determined if phase variation resulted in differences in expression of currently investigated conserved protein antigens. Using locked strains that express a single methyltransferase specificity, we found differences in clinically relevant traits, including survival in blood, and adherence to and invasion of human cells. We also observed differences in expression of numerous proteinaceous vaccine candidates, which complicates selection of antigens for inclusion in a universal protein-based pneumococcal vaccine. This study will inform vaccine design against S. pneumoniae by ensuring only stably expressed candidates are included in a rationally designed vaccine. S. pneumoniae is the world's foremost bacterial pathogen. S. pneumoniae encodes a phasevarion (phase-variable regulon), that results in differential expression of multiple genes. Previous work demonstrated that the pneumococcal SpnIII phasevarion switches between six different expression states, generating six unique phenotypic variants in a pneumococcal population. Here, we show that this phasevarion generates multiple phenotypic differences relevant to pathobiology. Importantly, expression of conserved protein antigens varies with phasevarion switching. As capsule expression, a major pneumococcal virulence factor, is also controlled by the phasevarion, our work will inform the selection of the best candidates to include in a rationally designed, universal pneumococcal vaccine.
Topics: Humans; Methyltransferases; Phase Variation; Pneumococcal Vaccines; Streptococcus pneumoniae; Virulence
PubMed: 35536022
DOI: 10.1128/spectrum.00916-22 -
Vaccine Jul 2021Invasive pneumococcal disease (IPD) is responsible for serious illnesses such as bacteremia, sepsis, meningitis, and pneumonia in young children, older adults, and...
Invasive pneumococcal disease (IPD) is responsible for serious illnesses such as bacteremia, sepsis, meningitis, and pneumonia in young children, older adults, and persons with immunocompromising conditions and often leads to death. Although the most recent pneumococcal conjugate vaccines (PCVs) have been designed to target serotypes identified as the primary causative agents of IPD, the epidemiological landscape continues to change stressing the need to develop new PCVs. We have developed an investigational 24-valent PCV (PCV24) including serotypes 1, 2, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F all conjugated to CRM197 and evaluated this vaccine in adult monkeys. PCV24 was shown to be immunogenic and induced functional antibody for all vaccine serotypes. Of the serotypes common to PCV13 and V114 (PCV15), PCV24 had a similar immunogenic response with the exceptions of 23F which had higher IgG GMCs for PCV13 and V114, and 7F which had higher GMCs for PCV13. Functional antibody responses were similar for the serotypes in common between PCV24, PCV13 and V114 vaccines, with the exception of serotype 7F which was greater for PCV13. Overall, this study shows that PCV24 provided similar immunogenicity as the lower valent vaccines in adult monkeys with no apparent serotype interference. In addition, PCV24 also provided protection against pneumococcal infection in a mouse challenge model.
Topics: Aged; Animals; Antibodies, Bacterial; Child, Preschool; Haplorhini; Humans; Infant; Mice; Pneumococcal Infections; Pneumococcal Vaccines; Vaccines, Conjugate
PubMed: 34074546
DOI: 10.1016/j.vaccine.2021.04.067 -
Hemoglobin May 2021Sickle cell disease is a genetic disease with a predisposition to infections caused by encapsulated organisms, especially Pneumococcal vaccines and prophylactic...
Sickle cell disease is a genetic disease with a predisposition to infections caused by encapsulated organisms, especially Pneumococcal vaccines and prophylactic penicillin have reduced the rate of this infection and mortality in sickle cell disease. However, implementation of these interventions is limited in Africa. The objectives of the study were to assess health care providers' behaviors with the implementation of pneumococcal vaccination and penicillin prophylaxis and to identify barriers to their use. A 25-item online questionnaire was administered through SickleinAfrica: a network of researchers, and healthcare providers, in Ghana, Nigeria, and Tanzania, working to improve health outcomes of sickle cell disease in Africa. Data was collected and managed using the Research Electronic Data Capture (REDCap), tools and data analysis was done using STATA version 13 and R statistical software. Eighty-two medical practitioners responded to the questionnaire. Only 54.0 and 48.7% of respondents indicated the availability of published guidelines on sickle cell disease management and pneumococcal vaccine use, respectively, at their facilities. The majority (54.0%) perceived that the vaccines are effective but over 20.0% were uncertain of their usefulness. All respondents from Ghana and Tanzania affirmed the availability of guidelines for penicillin prophylaxis in contrast to 44.1% in Nigeria. Eighty-five percent of respondents affirmed the need for penicillin prophylaxis but 15.0% had a contrary opinion for reasons including the rarity of isolation of in African studies, and therefore, the uncertainty of its benefit. Lack of published guidelines on the management of sickle cell disease and doubts about the necessity of prophylactic measures are potential barriers to the implementation of effective interventions.
Topics: Anemia, Sickle Cell; Health Personnel; Humans; Nigeria; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae
PubMed: 34355623
DOI: 10.1080/03630269.2021.1954943 -
Cellular and Molecular Biology... Jan 2022Streptococcus pneumoniae is the bacterium that causes pneumococcal disease which often results in pneumonia, meningitis, otitis media, septicemia and sinusitis.... (Review)
Review
Streptococcus pneumoniae is the bacterium that causes pneumococcal disease which often results in pneumonia, meningitis, otitis media, septicemia and sinusitis. Pneumonia, particularly, is a significant cause of worldwide morbidity and a global health burden as well. Treatment often relies on antimicrobials, to which the pathogen is frequently mutating and rendering infective. Consequently, vaccination is the most effective approach in dealing with pneumococcal antimicrobial resistance (AMR). Unfortunately, the current pneumococcal polysaccharide and conjugate vaccines have a narrow serotype coverage. Therefore, the current need for vaccines with a broader serotype coverage cannot be overstated. Pneumococcal Surface Protein A and C are potential vaccine candidate antigens present in over 90% of the strains from clinical isolates as well as laboratory non-encapsulated strains. Pneumococcal Surface Protein A is an active virulent factor that pneumococci use to evade complement-mediated host immune responses and has been shown to elicit immune responses against pneumococcal infections. This review explores the potential utilization of Pneumococcal Surface Protein A to immunize against S. pneumoniae.
Topics: Bacterial Proteins; Humans; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae
PubMed: 35809277
DOI: 10.14715/cmb/2021.67.4.32