A protective human monoclonal IgA antibody produced in vitro: Anti‐pneumococcal antibody engendered by Epstein‐Barr virus‐immortalized cell line

Abstract

Human lymphocytes that produce anti-pneumococcal antibodies were separated and immortalized by Epstein-Barr virus and then cloned. One clone (NAD-Sel) produces an IgA, kappa antibody which is specific for the polysaccharides of type 8 pneumococcus, while not reactive with any of the polysaccharides derived from 24 other pneumococcal strains. The antibody, which is present in the cell supernatant as monomer and polymer, binds to protein A and does not fix complement. When incubated in vitro with type 8 pneumococci, it induces direct killing and increases the opsonization of these bacteria by mouse macrophages.

Modulation of Polymorphonuclear Cell Interleukin-8 Secretion by Human Monoclonal Antibodies to Type 8 Pneumococcal Capsular Polysaccharide

“…The different opsonophagocytic killing abilities observed for NAD and serum IgA to type 14 PS could reflect type-specific differences, the different conditions or complement sources used, or the increased ability of polyclonal, polymeric IgA to promote alternative complement pathway activation (21,37). NAD consists of monomers and dimers (data not shown) and did not promote C3 deposition in this or a previous study that used another method (42). The results of the opsonophagocytosis experiments did not differ with the use of different conditions, some of which were similar to those used to study immune sera (45), and there was no evidence for a prozone-like phenomenon in which high amounts of antibody inhibit antibody function (16,47,49).…”

“…Opsonic type-specific IgG to the homologous serotype is known to be sufficient to confer protection in the immune host (34). Type-specific IgM and IgA have also been shown to mediate protection against pneumococci in different models (12,20,40,42,56). However, mechanisms of IgM and IgA efficacy are less well understood.…”

Killing of Streptococcus pneumoniae by capsular polysaccharide–specific polymeric IgA, complement, and phagocytes

“…Indeed, capsule-specific IgA comprised a greater proportion of pIgA than of mIgA. A human IgA mAb, produced in both monomeric and polymeric forms, has been described that reacts with type 8 S. pneumoniae and mediates a low level of phagocyte binding in the absence of complement (42). The same antibody induced significant protection of mice when administered systemically, although the mechanism of protection was not documented.…”

Immunogenicity and immunochemistry ofStreptococcus pneumoniae capsular polysaccharides

“…In pregnant women given immunoglobulin, transplacental passage of IgG occurs from the 34th week of gestation (Morell et al 1986). A monoclonal IgA,× antibody specific for $8 is produced by an Epstein-Barr virus immortalized cell line of human lymphocytes, which does not fix complement but induces direct killing of type 8 pneumococci in vitro and opsonization by mouse macrophages (Steinitz et al 1986). Such monoclonal antibodies are suitable for use in therapy, provided that they improve the recipient's immunity against the pathogen.…”