Complex Explanation

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Science  11 Oct 2002:
Vol. 298, Issue 5592, pp. 327
DOI: 10.1126/science.298.5592.327c

Every so often vaccines don't quite work as planned, as occurred in the 1960s when a vaccination program against respiratory syncytial virus (RSV) led to worse, rather than better, responses in children who subsequently were exposed to the virus. The primary cause of enhanced RSV disease was traced to the use of formalin as a means of inactivating the virus in vaccine preparations, although why this should adversely affect immunity to RSV remained unclear.

Polack et al. report that enhanced RSV disease in mice is characterized by deposition of antibody-containing immune complexes and by activation of components of the complement system; signs also detected in lung tissue preserved from affected children. Mice lacking either the complement component C3 or B cells did not develop enhanced RSV disease when immunized with formalin-inactivated RSV vaccine. The requirement for both antibodies and complement agrees with the interpretation that vaccination might stimulate excessive production of antibodies that, while failing to neutralize the virus itself, could nevertheless form immune complexes and activate complement-mediated damage in the lungs. Potentially, this could result from disruption of critical viral epitopes by formalin treatment or from diminished maturation of B cells that produce high-affinity antibodies. — SJS

J. Exp. Med.196, 859 (2002).

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