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The Journal of Immunology, 1972, 108: 622-632.
Copyright © 1972 by The American Association of Immunologists, Inc.

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Sensitization and Neutralization of Adenovirus by Specific Sera Against Capsid Subunits

Göran Wadell

Department of Virology, School of Medicine, Karolinska Institutet, Stockholm, Sweden

Abstract

The relative importance of the two different type-specific determinants (one on the hexons, the other on the distal part of the vertex projections) on the adenovirus capsid for the induction of antibodies capable of neutralizing virus infectivity in vitro was studied. Rabbit antisera against fibers or pentons displayed no demonstrable or low neutralizing activity when assayed by end point titration in tubes. Antisera against hexons of members of subgroup I and II and of serotype 4 consistently displayed high ratios of neutralizing capacity over type-specific complement fixation (CF) activity. However, sera against hexons of adenovirus types belonging to subgroup III showed a lower neutralizing capacity relative to type-specific CF activity. Two different populations of hexons of serotype 2 (subgroup III) could be separated by anion exchange chromatography and iso-electric focusing. Sera against certain preparations of hexons obtained by these techniques displayed very low neutralizing activity in spite of the presence of large amounts of type-specific CF antibodies.

Neutralization by sera against hexons of members of subgroup III (except type 4) was enhanced after addition of sheep anti-rabbit sera, whereas the high titers of the corresponding sera of the remaining serotypes remained unaffected. By employing the same technique, dramatic enhancement of the neutralizing capacity of sera against fibers or pentons of members of all subgroups was demonstrated. Fab and F(ab')2 fragments of hexon or fiber specific antibodies were totally devoid of virus-neutralizing activity but retained the capacity to interact with antigenic determinants on fibers and hexons as demonstrated by hemagglutination enhancement, hemagglutination inhibition and an antibody blocking test based on CF. Combined with sheep anti-rabbit antibodies, these virus-specific antibody fragments were capable of neutralizing adenovirus infectivity indicating that Fc fragments of virus-specific antibodies were not required.







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