• Timothy J Wells, Deborah Whitters, Yanina R Sevastsyanovich, Jennifer N Heath, John Pravin, Margaret Goodall, Douglas F Browning, Matthew K O'Shea, Amy Cranston, Anthony De Soyza, Adam F Cunningham, Calman A MacLennan, Ian R Henderson, and Robert A Stockley.
• Institute of Microbiology and Infection, School of Immunity and Infection, School Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, England, UK Institute of Microbiology and Infection, School of Immunity and Infection, School Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, England, UK.
• J. Exp. Med. 2014 Aug 25; 211 (9): 1893-904.

AbstractAlthough specific antibody induced by pathogens or vaccines is a key component of protection against infectious threats, some viruses, such as dengue, induce antibody that enhances the development of infection. In contrast, antibody-dependent enhancement of bacterial infection is largely unrecognized. Here, we demonstrate that in a significant portion of patients with bronchiectasis and Pseudomonas aeruginosa lung infection, antibody can protect the bacterium from complement-mediated killing. Strains that resist antibody-induced, complement-mediated killing produce lipopolysaccharide containing O-antigen. The inhibition of antibody-mediated killing is caused by excess production of O-antigen-specific IgG2 antibodies. Depletion of IgG2 to O-antigen restores the ability of sera to kill strains with long-chain O-antigen. Patients with impaired serum-mediated killing of P. aeruginosa by IgG2 have poorer respiratory function than infected patients who do not produce inhibitory antibody. We suggest that excessive binding of IgG2 to O-antigen shields the bacterium from other antibodies that can induce complement-mediated killing of bacteria. As there is significant sharing of O-antigen structure between different Gram-negative bacteria, this IgG2-mediated impairment of killing may operate in other Gram-negative infections. These findings have marked implications for our understanding of protection generated by natural infection and for the design of vaccines, which should avoid inducing such blocking antibodies. © 2014 Wells et al.

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