Comparison of Functional Activities between IgG1 and IgM Class-Switched Human Monoclonal Antibodies Reactive with Group B Streptococci or Escherichia coli K1

Raff, Howard V.; Bradley, Cheryl; Brady, William; Donaldson, Karen; Lipsich, Leah; Maloney, Grace; Shuford, Walter W.; Walls, Michael A.; Ward, Pamela J.; Wolff, E; Harris, Linda J.

doi:10.1093/infdis/163.2.346

Cited by 39 publications

(34 citation statements)

References 33 publications

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“…On the other hand, the chIgM antibodies had at least a 50-times-higher OP activity on a molar basis than chIgG3 in our test system. A similar high OP activity of human chIgM over human IgG1 has been observed for anticarbohydrate antibodies against the Gram-positive group B streptococci [33,34].…”

Section: Discussionsupporting

confidence: 68%

Binding properties and anti-bacterial activities of V-region identical, human IgG and IgM antibodies, against group B Neisseria meningitidis

Michaelsen

Ihle

Beckstrøm

et al. 2003

Biochemical Society Transactions

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We have constructed chimaeric (ch) mouse/human antibodies with identical binding regions isolated from the V-genes of two mouse parent hybridoma cell lines, with specificity against the P1.7 and P1.16 epitopes on the outer-membrane protein PorA on meningococci. The chimaeric antibodies can be used to analyse relationships between specificity, binding activity (avidity and kinetics), isotype (antibody class and antibody subclass) and in vitro anti-bacterial activity of meningococcal antibodies. The antibody sets represented the human isotypes IgG1, IgG3 and IgM, which dominate during immune response against protein antigens. The binding activities were quite similar for all these isotypes, surprisingly also for the pentameric IgM. Interestingly, monomeric IgM, prepared from pentameric IgM by partially reduction and alkylation, had similar binding activities as the original pentameric IgM. Regarding in vitro anti-bacterial activity, chIgG1 was superior in SBA (serum bactericidal activity) compared with chIgG3, while chIgG3 was more efficient in OP (opsonophagocytosis; measured by flow cytometry) than chIgG1. ChIgM showed slightly higher SBA than chIgG1 on molar basis, and much higher OP than chIgG3 and chIgG1. A lower concentration of antibodies was needed against the P1.16 than against the P1.7 epitope to induce SBA, but this was not the case for OP.

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Section: Discussionsupporting

confidence: 68%

Binding properties and anti-bacterial activities of V-region identical, human IgG and IgM antibodies, against group B Neisseria meningitidis

Michaelsen

Ihle

Beckstrøm

et al. 2003

Biochemical Society Transactions

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“…In contrast, low levels of anti-PPS IgM antibodies can account for the functional difference observed between young and old adults immunized with PPV23, since IgM is more efficient at fixing complement than IgG. Indeed, studies with human monoclonal antibodies have shown that IgM antibodies can be 10-to 100-fold more effective than IgG antibodies at opsonizing bacteria or protecting animals from infections (30,39). Some IgM antibodies that are protective against bacterial infections bind many unrelated antigens, such as singlestranded DNA, thyroglobulin, and ␤-galactosidase (27).…”

Section: Discussionmentioning

confidence: 99%

Older Adults Have a Low Capacity To Opsonize Pneumococci Due to Low IgM Antibody Response to Pneumococcal Vaccinations

2011

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Since the 23-valent pneumococcal polysaccharide vaccine (PPV23) is less effective for older adults than for young adults, it is important to investigate the immunologic basis for the reduced efficacy of PPV23 among older adults. We determined the effectiveness of PPV23 among young (n ‫؍‬ 55) and older (n ‫؍‬ 44) adults by measuring the serum IgG, IgM, and IgA concentrations and opsonic capacities against serotypes 14, 18C, and 23F. While young and older adults showed no difference in levels of IgG antibodies against pneumococcal polysaccharide (PPS), older adults had lower IgA and IgM antibody levels than young adults for all three serotypes. In both age groups, anti-PPS IgA or IgM antibody levels were much lower than anti-PPS IgG antibody levels. Young adults showed higher opsonic capacities than older adults for serotypes 14 and 23F. In order to determine the effects of anti-PPS IgA or IgM antibodies on the functional difference between young and older adults, anti-PPS IgA or IgM antibodies were removed from immune sera by affinity chromatography. The difference in opsonic capacity between young and older adults disappeared for serotypes 14 and 23F (but not for serotype 18C) when IgM antibody was removed. However, there was no significant difference between the two age groups when IgA antibody was removed. In conclusion, even though anti-PPS IgG antibody levels are high compared with anti-PPS IgM antibody levels, the low levels of anti-PPS IgM antibody alone can explain the functional difference observed between young and older adults immunized with PPV23 with regard to some pneumococcal serotypes.

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“…Furthermore, expressing a mAb as a multivalent isotype, such as SIgA or IgM, can dramatically enhance the potency of an antibody by increasing the avidity (96) or agglutination activity (14). For example, an anti- Escherichia coli IgM was 1,000-fold more effective in protecting neonatal rats than its class-switched IgG (both in vitro and in vivo) (41). From a commercial standpoint, a 1,000-fold increase in avidity could translate into a 1,000-fold decrease in dose and subsequent cost.…”

Section: Recent Advances In Mab Technologymentioning

confidence: 99%

Using Monoclonal Antibodies to Prevent Mucosal Transmission of Epidemic Infectious Diseases

Zeitlin

Cone

Whaley

1999

Emerg. Infect. Dis.

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Passive immunization with antibodies has been shown to prevent a wide variety of diseases. Recent advances in monoclonal antibody technology are enabling the development of new methods for passive immunization of mucosal surfaces. Human monoclonal antibodies, produced rapidly, inexpensively, and in large quantities, may help prevent respiratory, diarrheal, and sexually transmitted diseases on a public health scale.

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Comparison of Functional Activities between IgG1 and IgM Class-Switched Human Monoclonal Antibodies Reactive with Group B Streptococci or Escherichia coli K1

Cited by 39 publications

References 33 publications

Binding properties and anti-bacterial activities of V-region identical, human IgG and IgM antibodies, against group B Neisseria meningitidis

Binding properties and anti-bacterial activities of V-region identical, human IgG and IgM antibodies, against group B Neisseria meningitidis

Older Adults Have a Low Capacity To Opsonize Pneumococci Due to Low IgM Antibody Response to Pneumococcal Vaccinations

Using Monoclonal Antibodies to Prevent Mucosal Transmission of Epidemic Infectious Diseases

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