Elevated Levels of IgG2 Antibodies Protect Some Types of Gram-Negative Bacteria

The finding that an overabundance of a certain class of antibodies protects some bacteria from the effects of antibiotics has marked implications for our understanding of the protection generated by natural infections and for the design of vaccines, which should avoid inducing such inhibitory antibodies.

Investigators at the University of Birmingham (United Kingdom) worked with patients that had bronchiectasis—a chronic infection characterized by persistent cough, shortness of breath, and chest pain—or lung infection caused by the bacterium Pseudomonas aeruginosa.

They reported in the August 2014 online edition of the Journal of Experimental Medicine that in a significant portion of these patients, antibodies protected the bacterium from complement-mediated killing. Strains that resisted antibody-induced, complement-mediated killing produced a lipopolysaccharide containing O-antigen. In particular, they found that inhibition of antibody-mediated killing was caused by excess production of O-antigen–specific antibodies of the IgG2 class. Depletion of IgG2 to O-antigen restored the ability of sera to kill strains with long-chain O-antigen.

Patients with impaired serum-mediated killing of P. aeruginosa by IgG2 were shown to have poorer respiratory function than infected patients who did not produce the inhibitory antibody.

The authors suggested that excessive binding of IgG2 to O-antigen shielded the bacterium from other antibodies that could induce complement-mediated killing. Since there is significant sharing of O-antigen structure between different Gram-negative bacteria, this IgG2-mediated impairment of killing could be operating in other Gram-negative infections as well. These findings have marked implications for understanding the nature of protection generated by natural infections and for the design of vaccines, which should avoid inducing IgG2 class inhibitory antibodies.

Related Links:
University of Birmingham