Immunization with PhtD truncated fragments reduces nasopharyngeal colonization by Streptococcus pneumoniae

André, Greiciely O.; Assoni, Lucas; Rodríguez, Dunia; Leite, Luciana Cezar de Cerqueira; Santos, Thaisy E.P. dos; Ferraz, Lúcio Fábio Caldas; Converso, Thiago Rojas; Darrieux, Michelle

doi:10.1016/j.vaccine.2020.04.050

Cited by 11 publications

(9 citation statements)

References 29 publications

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“…PhtD has been shown to protect against systemic pneumococcal disease in a mouse model ( 29 ), and immunization of rhesus macaques with PhtD along with detoxified pneumolysin protected the animals against pneumococcal infection ( 41 ). Fragments of PhtD have also been assessed for protective efficacy, and somewhat conflicting reports have demonstrated that both the N and C terminus are immunogenic and protective ( 42 , 43 ). PhtD was recently used as an antigen in a phase IIb clinical trial, demonstrating that PhtD remains an antigen of interest in pneumococcal vaccinology, although PhtD was administered along with PCV13, so a direct comparison of PhtD versus PCV13 was not accomplished ( 44 ).…”

Section: Introductionmentioning

confidence: 99%

Broadly Reactive Human Monoclonal Antibodies Targeting the Pneumococcal Histidine Triad Protein Protect against Fatal Pneumococcal Infection

et al. 2021

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Streptococcus pneumoniae remains a leading cause of bacterial pneumonia despite the widespread use of vaccines. While vaccines are effective at reducing the incidence of most serotypes included in vaccines, a rise in infection due to nonvaccine serotypes and moderate efficacy against some vaccine serotypes have contributed to high disease incidence. Additionally, numerous isolates of S. pneumoniae are antibiotic or multidrug resistant. Several conserved pneumococcal proteins prevalent in the majority of serotypes have been examined for their potential as vaccines in preclinical and clinical trials. An additional, yet-unexplored tool for disease prevention and treatment is the use of human monoclonal antibodies (MAbs) targeting conserved pneumococcal proteins. Here, we isolated the first human MAbs (PhtD3, PhtD6, PhtD7, PhtD8, and PspA16) against the pneumococcal histidine triad protein (PhtD) and the pneumococcal surface protein A (PspA), two conserved and protective antigens. MAbs to PhtD target diverse epitopes on PhtD, and MAb PspA16 targets the N-terminal segment of PspA. The PhtD-specific MAbs bind to multiple serotypes, while MAb PspA16 serotype breadth is limited. MAbs PhtD3 and PhtD8 prolong the survival of mice infected with pneumococcal serotype 3. Furthermore, MAb PhtD3 prolongs the survival of mice in intranasal and intravenous infection models with pneumococcal serotype 4 and in mice infected with pneumococcal serotype 3 when administered 24 h after pneumococcal infection. All PhtD and PspA MAbs demonstrate opsonophagocytic activity, suggesting a potential mechanism of protection. Our results identify new human MAbs for pneumococcal disease prevention and treatment and identify epitopes on PhtD and PspA recognized by human B cells.

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Section: Introductionmentioning

confidence: 99%

Broadly Reactive Human Monoclonal Antibodies Targeting the Pneumococcal Histidine Triad Protein Protect against Fatal Pneumococcal Infection

et al. 2021

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“…PhtD can also reduce complement deposition via Factor H (FH) (Ogunniyi et al, 2009). Several studies have demonstrated that immunization with PhtD or other Pht antigens elicits antibodies that protect against sepsis, pneumonia, and reduced colonization in animal models (Wizemann et al, 2001;Denoël et al, 2011a;Denoël et al, 2011b;Godfroid et al, 2011;Plumptre et al, 2013b;Ravinder et al, 2014;Papastamatiou et al, 2018;Andréet al, 2020). In a non-human primate model, vaccination with a combined PhtD/pneumolysin formulation was protective against lethal challenge (Denoël et al, 2011b).…”

Section: Pneumococcal Histidine Triad Proteinsmentioning

confidence: 99%

Diverse Mechanisms of Protective Anti-Pneumococcal Antibodies

Gingerich

Mousa

2022

Front. Cell. Infect. Microbiol.

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The gram-positive bacterium Streptococcus pneumoniae is a leading cause of pneumonia, otitis media, septicemia, and meningitis in children and adults. Current prevention and treatment efforts are primarily pneumococcal conjugate vaccines that target the bacterial capsule polysaccharide, as well as antibiotics for pathogen clearance. While these methods have been enormously effective at disease prevention and treatment, there has been an emergence of non-vaccine serotypes, termed serotype replacement, and increasing antibiotic resistance among these serotypes. To combat S. pneumoniae, the immune system must deploy an arsenal of antimicrobial functions. However, S. pneumoniae has evolved a repertoire of evasion techniques and is able to modulate the host immune system. Antibodies are a key component of pneumococcal immunity, targeting both the capsule polysaccharide and protein antigens on the surface of the bacterium. These antibodies have been shown to play a variety of roles including increasing opsonophagocytic activity, enzymatic and toxin neutralization, reducing bacterial adherence, and altering bacterial gene expression. In this review, we describe targets of anti-pneumococcal antibodies and describe antibody functions and effectiveness against S. pneumoniae.

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“…PspA Cell surface (Lu et al, 2015) PsaA Cell surface (Lu et al, 2015) Pht family Cell surface (Khan and Pichichero, 2012;Andréet al, 2020;Malekan et al, 2020) Ply Cytosol (Alexander et al, 1994;Thanawastien et al, 2021) LytB Cell surface (Corsini et al, 2016) activity. Moreover, an immunogenicity and safety clinical trial was performed in adults ≥ 65 years of age in February 2020 with an enrollment of 875 participants, people who received PREVNAR 20 showed no severe adverse effects like fever, muscular pain, among others (NCT03835975).…”

Section: Antigen Localization Referencementioning

confidence: 99%

Non-capsular based immunization approaches to prevent Streptococcus pneumoniae infection

Silva

Vázquez

Campusano

et al. 2022

Front. Cell. Infect. Microbiol.

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Streptococcus pneumoniae is a Gram-positive bacterium and the leading cause of bacterial pneumonia in children and the elderly worldwide. Currently, two types of licensed vaccines are available to prevent the disease caused by this pathogen: the 23-valent pneumococcal polysaccharide-based vaccine and the 7-, 10, 13, 15 and 20-valent pneumococcal conjugate vaccine. However, these vaccines, composed of the principal capsular polysaccharide of leading serotypes of this bacterium, have some problems, such as high production costs and serotype-dependent effectiveness. These drawbacks have stimulated research initiatives into non-capsular-based vaccines in search of a universal vaccine against S. pneumoniae. In the last decades, several research groups have been developing various new vaccines against this bacterium based on recombinant proteins, live attenuated bacterium, inactivated whole-cell vaccines, and other newer platforms. Here, we review and discuss the status of non-capsular vaccines against S. pneumoniae and the future of these alternatives in a post-pandemic scenario.

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Immunization with PhtD truncated fragments reduces nasopharyngeal colonization by Streptococcus pneumoniae

Cited by 11 publications

References 29 publications

Broadly Reactive Human Monoclonal Antibodies Targeting the Pneumococcal Histidine Triad Protein Protect against Fatal Pneumococcal Infection

Broadly Reactive Human Monoclonal Antibodies Targeting the Pneumococcal Histidine Triad Protein Protect against Fatal Pneumococcal Infection

Diverse Mechanisms of Protective Anti-Pneumococcal Antibodies

Non-capsular based immunization approaches to prevent Streptococcus pneumoniae infection

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