The modified surface killing assay distinguishes between protective and nonprotective antibodies to PspA

Academic Article

Abstract

  • © 2019 Genschmer et al. Pneumococcal surface protein A (PspA) elicits antibody protective against lethal challenge by Streptococcus pneumoniae and is a candidate noncapsular antigen for inclusion in vaccines. Evaluation of immunity to PspA in human trials would be greatly facilitated by an in vitro functional assay able to distinguish protective from nonprotective antibodies to PspA. Mouse monoclonal antibodies (MAbs) to PspA can mediate killing by human granulocytes in the modified surface killing assay (MSKA). To determine if the MSKA can distinguish between protective and nonprotective MAbs, we examined seven MAbs to PspA. All bound recombinant PspA, as detected by enzyme-linked immunosorbent assay and Western blotting; four gave strong passive protection against fatal challenge, two were nonprotective, and the seventh one only delayed death. The four that were able to provide strong passive protection were also most able to enhance killing in the MSKA, the two that were not protective in mice were not effective in the MSKA, and the MAb that was only weakly protective in mice was weakly effective in the MSKA (P<0.001). One of the four most protective MAbs tested reacted to the prolinerich domain of PspA. Two of the other most protective MAbs and the weakly protective MAb reacted with a fragment from PspA's <-helical domain (
  • Published In

  • mSphere  Journal
  • Digital Object Identifier (doi)

    Author List

  • Genschmer KR; Vadesilho CFM; McDaniel LS; Park SS; Hale Y; Miyaji EN; Briles DE
  • Volume

  • 4
  • Issue

  • 6