Diverse Mechanisms of Protective Anti-Pneumococcal Antibodies

Abstract

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.

PCV13, PCV15 or PCV20: Which vaccine is best for children in terms of immunogenicity?

“…The approach selected here to compare immune responses in different trials have also been used in a recently published paper comparing OPA responses following one PCV15 dose or one PCV20 dose in adults, although a more sophisticated statistical analysis was performed in the comparison (( 16 )). The OPA measurement is recognized as a better predictor of the clinical effectiveness of PCVs than anti-capsular polysaccharide antibody levels determined by the enzyme-linked immunosorbent assay (ELISA), although the latter method has the advantage of being standardized for inter-laboratory comparisons (( 17 , 18 )). Mean geometric OPA titres cannot be compared between different laboratories and between different serotypes in a same laboratory.…”

Characterization of the innate immune response to Streptococcus pneumoniae infection in zebrafish

“…those with genetic or acquired immunodeficiencies, for example, due to defects in antibody production, HIV infection, or transplantation [20,86]. While antibodies against capsule polysaccharide and protein antigens are the main components of protective immunity to pneumococcus, defects in innate mechanisms, especially the complement system and TLR signaling, have also been associated with increased susceptibility to invasive pneumococcal infection [20,87,88]. Complement activation and the subsequent opsonophagocytosis, in particular, are critical in the clearance of pneumococcus, as has been shown in multiple knockout studies in murine models of pneumococcal infection [89][90][91][92][93][94][95][96].…”

Patient-Derived Antibody Data Yields Development of Broadly Cross-Protective Monoclonal Antibody against ST258 Carbapenem-Resistant Klebsiella pneumoniae

“…The capsular polysaccharide (CPS) constitutes an important virulence factor of Klebsiella that promotes resistance to phagocytosis and serum bactericidal activity. It has been a useful immunogenic target in other organisms ( 8 – 10 ). However, antigenic diversity limits the use of monoclonal antibody as a broader therapy.…”