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Immunology Apr 2021Antibodies are a key element of the immune response. They can bind their molecular targets with exquisite sensitivity and specificity, providing protection against a...
Antibodies are a key element of the immune response. They can bind their molecular targets with exquisite sensitivity and specificity, providing protection against a multitude of pathogens. They have long been understood to be markers of a successful response to vaccination, and are now widely manufactured as highly specific and robust immunotherapeutic agents. Less well understood are the polyreactive antibodies, found in serum, which are able to bind more than one target molecule. Here, we highlight new research into these naturally occurring polyreactive antibodies, which demonstrates their importance for protection against Streptococcus pneumoniae, a common cause of airway infection.
Topics: Animals; Antibodies, Bacterial; Antibody Formation; Epitopes; Humans; Pneumococcal Infections; Streptococcus pneumoniae; Vaccination
PubMed: 33729558
DOI: 10.1111/imm.13324 -
Emerging Infectious Diseases Sep 2023Streptococcus pneumoniae can co-infect persons who have viral respiratory tract infections. However, research on S. pneumoniae infections that are temporally associated...
Streptococcus pneumoniae can co-infect persons who have viral respiratory tract infections. However, research on S. pneumoniae infections that are temporally associated with SARS-CoV-2 infections is limited. We described the epidemiology and clinical course of patients who had invasive pneumococcal disease (IPD) and temporally associated SARS-CoV-2 infections in Alaska, USA, during January 1, 2020-December 23, 2021. Of 271 patients who had laboratory-confirmed IPD, 55 (20%) had a positive SARS-CoV-2 test result. We observed no major differences in age, race, sex, or underlying medical conditions among IPD patients with and without SARS-CoV-2. However, a larger proportion of IPD patients with SARS-CoV-2 died (16%, n = 9) than for those with IPD alone (4%, n = 9) (p<0.01). IPD patients with SARS-CoV-2 were also more likely to be experiencing homelessness (adjusted OR 3.5; 95% CI 1.7-7.5). Our study highlights the risk for dual infection and ongoing benefits of pneumococcal and COVID-19 vaccination, especially among vulnerable populations.
Topics: Humans; Alaska; COVID-19 Vaccines; COVID-19; SARS-CoV-2; Pneumococcal Infections; Streptococcus pneumoniae; Pneumococcal Vaccines
PubMed: 37506683
DOI: 10.3201/eid2909.230080 -
Emerging Infectious Diseases Oct 2023Ongoing surveillance after pneumococcal conjugate vaccination (PCV) deployment is essential to inform policy decisions and monitor serotype replacement. We report... (Review)
Review
Ongoing surveillance after pneumococcal conjugate vaccination (PCV) deployment is essential to inform policy decisions and monitor serotype replacement. We report serotype and disease severity trends in 3,719 adults hospitalized for pneumococcal disease in Bristol and Bath, United Kingdom, during 2006–2022. Of those cases, 1,686 were invasive pneumococcal disease (IPD); 1,501 (89.0%) had a known serotype. IPD decreased during the early COVID-19 pandemic but during 2022 gradually returned to prepandemic levels. Disease severity changed throughout this period: CURB65 severity scores and inpatient deaths decreased and ICU admissions increased. PCV7 and PCV13 serotype IPD decreased from 2006–2009 to 2021–2022. However, residual PCV13 serotype IPD remained, representing 21.7% of 2021–2022 cases, indicating that major adult PCV serotype disease still occurs despite 17 years of pediatric PCV use. Percentages of serotype 3 and 8 IPD increased, and 19F and 19A reemerged. In 2020–2022, a total of 68.2% IPD cases were potentially covered by PCV20.
Topics: Adult; Humans; Serogroup; Patient Acuity; Pneumococcal Infections; United Kingdom
PubMed: 37735739
DOI: 10.3201/eid2910.230519 -
Trends in Microbiology Dec 2022Streptococcus pneumoniae is a major cause of pneumonia, meningitis, and septicaemia worldwide. Pneumococcal antimicrobial resistance (AMR) has been highlighted by the... (Review)
Review
Streptococcus pneumoniae is a major cause of pneumonia, meningitis, and septicaemia worldwide. Pneumococcal antimicrobial resistance (AMR) has been highlighted by the WHO as an important public health concern, with emerging serotypes showing resistance to multiple antibiotics. Indeed, although the introduction of pneumococcal conjugate vaccines (PCVs) has been associated with an overall decline in pneumococcal AMR, there have been increases in prevalence of potentially disease-causing AMR serotypes not targeted by vaccination. Here, we discuss a variety of evolutionary mechanisms at the host, pathogen, and environmental levels that may contribute to changes in the prevalence of pneumococcal AMR in the post-vaccination era. The relative importance of these factors may vary by population, pneumococcal lineage, geography, and time, leading to the complex relationship between vaccination, antibiotic use, and AMR.
Topics: Humans; Infant; Streptococcus pneumoniae; Pneumococcal Infections; Anti-Bacterial Agents; Drug Resistance, Bacterial; Pneumococcal Vaccines; Vaccination
PubMed: 35843855
DOI: 10.1016/j.tim.2022.06.001 -
ELife Jul 2022The characteristics of pneumococcal carriage vary between infants and adults. Host immune factors have been shown to contribute to these age-specific differences, but... (Meta-Analysis)
Meta-Analysis
The characteristics of pneumococcal carriage vary between infants and adults. Host immune factors have been shown to contribute to these age-specific differences, but the role of pathogen sequence variation is currently less well-known. Identification of age-associated pathogen genetic factors could leadto improved vaccine formulations. We therefore performed genome sequencing in a large carriage cohort of children and adults and combined this with data from an existing age-stratified carriage study. We compiled a dictionary of pathogen genetic variation, including serotype, strain, sequence elements, single-nucleotide polymorphisms (SNPs), and clusters of orthologous genes (COGs) for each cohort - all of which were used in a genome-wide association with host age. Age-dependent colonization showed weak evidence of being heritable in the first cohort ( = 0.10, 95% CI 0.00-0.69) and stronger evidence in the second cohort ( = 0.56, 95% CI 0.23-0.87). We found that serotypes and genetic background (strain) explained a proportion of the heritability in the first cohort ( = 0.07, 95% CI 0.04-0.14 and = 0.06, 95% CI 0.03-0.13) and the second cohort ( = 0.11, 95% CI 0.05-0.21 and = 0.20, 95% CI 0.12-0.31). In a meta-analysis of these cohorts, we found one candidate association (p=1.2 × 10) upstream of an accessory Sec-dependent serine-rich glycoprotein adhesin. Overall, while we did find a small effect of pathogen genome variation on pneumococcal carriage between child and adult hosts, this was variable between populations and does not appear to be caused by strong effects of individual genes. This supports proposals for adaptive future vaccination strategies that are primarily targeted at dominant circulating serotypes and tailored to the composition of the pathogen populations.
Topics: Adult; Carrier State; Child; Genome-Wide Association Study; Humans; Infant; Nasopharynx; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Streptococcus pneumoniae
PubMed: 35881438
DOI: 10.7554/eLife.69244 -
FEBS Letters Aug 2020Streptococci are a broad group of Gram-positive bacteria. This genus includes various human pathogens causing significant morbidity and mortality. Two of the most... (Review)
Review
Streptococci are a broad group of Gram-positive bacteria. This genus includes various human pathogens causing significant morbidity and mortality. Two of the most important human pathogens are Streptococcus pneumoniae (pneumococcus) and Streptococcus pyogenes (group A streptococcus or GAS). Streptococcal pathogens have evolved to express virulence factors that enable them to evade complement-mediated attack. These include factor H-binding M (S. pyogenes) and pneumococcal surface protein C (PspC) (S. pneumoniae) proteins. In addition, S. pyogenes and S. pneumoniae express cytolysins (streptolysin and pneumolysin), which are able to destroy host cells. Sometimes, the interplay between streptococci, the complement, and antistreptococcal immunity may lead to an excessive inflammatory response or autoimmune disease. Understanding the fundamental role of the complement system in microbial clearance and the bacterial escape mechanisms is of paramount importance for understanding microbial virulence, in general, and, the conversion of commensals to pathogens, more specifically. Such insights may help to identify novel antibiotic and vaccine targets in bacterial pathogens to counter their growing resistance to commonly used antibiotics.
Topics: Animals; Anti-Bacterial Agents; Autoimmunity; Bacterial Proteins; Complement System Proteins; Humans; Immune Evasion; Inflammation; Pneumococcal Infections; Streptococcus pneumoniae; Streptococcus pyogenes
PubMed: 32594520
DOI: 10.1002/1873-3468.13872 -
Emerging Microbes & Infections Dec 2023Pneumococcal disease is a major threat to public health globally, impacting individuals across all age groups, particularly infants and elderly individuals. The use of...
Pneumococcal disease is a major threat to public health globally, impacting individuals across all age groups, particularly infants and elderly individuals. The use of current vaccines has led to unintended consequences, including serotype replacement, leading to a need for a new approach to combat pneumococcal disease. A promising solution is the development of a broad-spectrum pneumococcal vaccine. In this study, we present the development of a broad-spectrum protein-based pneumococcal vaccine that contains three pneumococcal virulence factors: rlipo-PsaA (lipidated form), rPspAΔC (truncated form), and rPspCΔC (truncated form). Intranasal immunization with rlipo-PsaA, rPspAΔC, and rPspCΔC (LAAC) resulted in significantly higher IgG titres than those induced by administration of nonlipidated rPsaA, rPspAΔC, and rPspCΔC (AAC). Furthermore, LAAC immunization induced the production of higher IgA titres in vaginal washes, feces, and sera in mice, indicating that LAAC can induce systemic mucosal immunity. In addition, administration of LAAC also induced Th1/Th17-biased immune responses and promoted opsonic phagocytosis of strains of various serotypes, implying that the immunogenicity of LAAC immunization provides a protective effect against pneumococcal infection. Importantly, challenge data showed that the LAAC-immunized mice had a reduced bacterial load not only for several serotypes of the 13-valent conjugate pneumococcal vaccine (PCV13) but also for selected non-PCV13 serotypes. Consistently, LAAC immunization increased the survival rate of mice after bacterial challenge with both PCV13 and non-PCV13 serotypes. In conclusion, our protein-based pneumococcal vaccine provides protective effects against a broad spectrum of serotypes.
Topics: Humans; Infant; Female; Mice; Animals; Aged; Streptococcus pneumoniae; Immunity, Mucosal; Pneumococcal Vaccines; Pneumococcal Infections; Immunization; Antibodies, Bacterial
PubMed: 37855122
DOI: 10.1080/22221751.2023.2272656 -
MBio Aug 2023() frequently causes secondary pneumonia after influenza A virus (IAV) infection, leading to high morbidity and mortality worldwide. Concomitant pneumococcal and...
() frequently causes secondary pneumonia after influenza A virus (IAV) infection, leading to high morbidity and mortality worldwide. Concomitant pneumococcal and influenza vaccination improves protection against coinfection but does not always yield complete protection. Impaired innate and adaptive immune responses have been associated with attenuated bacterial clearance in influenza virus-infected hosts. In this study, we showed that preceding low-dose IAV infection caused persistent infection and suppression of bacteria-specific T-helper type 17 (Th17) responses in mice. Prior infection protected against subsequent IAV/ coinfection by improving bacterial clearance and rescuing bacteria-specific Th17 responses in the lungs. Furthermore, blockade of IL-17A by anti-IL-17A antibodies abrogated the protective effect of preinfection. Importantly, memory Th17 responses induced by preinfection overcame viral-driven Th17 inhibition and provided cross-protection against different serotypes following coinfection with IAV. These results indicate that bacteria-specific Th17 memory cells play a key role in providing protection against IAV/ coinfection in a serotype-independent manner and suggest that a Th17-based vaccine would have excellent potential to mitigate disease caused by coinfection. IMPORTANCE () frequently causes secondary bacterial pneumonia after influenza A virus (IAV) infection, leading to increased morbidity and mortality worldwide. Current pneumococcal vaccines induce highly strain-specific antibody responses and provide limited protection against IAV/ coinfection. Th17 responses are broadly protective against single infection, but whether the Th17 response, which is dramatically impaired by IAV infection in naïve mice, might be effective in immunization-induced protection against pneumonia caused by coinfection is not known. In this study, we have revealed that -specific memory Th17 cells rescue IAV-driven inhibition and provide cross-protection against subsequent lethal coinfection with IAV and different serotypes. These results indicate that a Th17-based vaccine would have excellent potential to mitigate disease caused by IAV/ coinfection.
Topics: Animals; Mice; Humans; Pneumonia, Pneumococcal; Influenza, Human; Th17 Cells; Coinfection; Orthomyxoviridae Infections; Streptococcus pneumoniae; Pneumococcal Infections; Influenza Vaccines; Influenza A virus
PubMed: 37222516
DOI: 10.1128/mbio.00519-23 -
Frontiers in Cellular and Infection... 2021(also called pneumococcus) is not only a commensal that frequently colonizes the human upper respiratory tract but also a pathogen that causes pneumonia, sepsis, and... (Review)
Review
(also called pneumococcus) is not only a commensal that frequently colonizes the human upper respiratory tract but also a pathogen that causes pneumonia, sepsis, and meningitis. The mechanism of pneumococcal infection has been extensively studied, but the process of transmission has not been fully elucidated because of the lack of tractable animal models. Novel animal models of transmission have enabled further progress in investigating pneumococcal transmission mechanisms including the processes such as pneumococcal shedding, survival in the external environment, and adherence to the nasopharynx of a new host. Herein, we present a review on these animal models, recent research findings about pneumococcal transmission, and factors influencing the host-pneumococcus interaction.
Topics: Animals; Humans; Meningitis; Nasopharynx; Pneumococcal Infections; Pneumonia; Streptococcus pneumoniae
PubMed: 33996623
DOI: 10.3389/fcimb.2021.639450 -
PloS One 2023Experimental Human Pneumococcal Challenge (EHPC) involves the controlled exposure of adults to a specific antibiotic-sensitive Streptococcus pneumoniae serotype, to... (Review)
Review Meta-Analysis
INTRODUCTION
Experimental Human Pneumococcal Challenge (EHPC) involves the controlled exposure of adults to a specific antibiotic-sensitive Streptococcus pneumoniae serotype, to induce nasopharyngeal colonisation for the purpose of vaccine research. The aims are to review comprehensively the safety profile of EHPC, explore the association between pneumococcal colonisation and frequency of safety review and describe the medical intervention required to undertake such studies.
METHODS
A single-centre review of all EHPC studies performed 2011-2021. All recorded serious adverse events (SAE) in eligible studies are reported. An unblinded meta-analysis of collated anonymised individual patient data from eligible EHPC studies was undertaken to assess the association between experimental pneumococcal colonisation and the frequency of safety events following inoculation.
RESULTS
In 1416 individuals (median age 21, IQR 20-25), 1663 experimental pneumococcal inoculations were performed. No pneumococcal-related SAE have occurred. 214 safety review events were identified with 182 (12.85%) participants presenting with symptoms potentially in keeping with pneumococcal infection, predominantly in pneumococcal colonised individuals (colonised = 96/658, non-colonised = 86/1005, OR 1.81 (95% CI 1.28-2.56, P = <0.001). The majority were mild (pneumococcal group = 72.7% [120/165 reported symptoms], non-pneumococcal = 86.7% [124/143 reported symptoms]). 1.6% (23/1416) required antibiotics for safety.
DISCUSSION
No SAEs were identified directly relating to pneumococcal inoculation. Safety review for symptoms was infrequent but occurred more in experimentally colonised participants. Most symptoms were mild and resolved with conservative management. A small minority required antibiotics, notably those serotype 3 inoculated.
CONCLUSION
Outpatient human pneumococcal challenge can be conducted safely with appropriate levels of safety monitoring procedures in place.
Topics: Adult; Humans; Young Adult; Streptococcus pneumoniae; Pneumococcal Infections; Pneumococcal Vaccines; Nasopharynx; Anti-Bacterial Agents
PubMed: 37141259
DOI: 10.1371/journal.pone.0284399