The Modified Surface Killing Assay Distinguishes between Protective and Nonprotective Antibodies to PspA

Abstract

The most important finding of this study is that the MSKA can be used as an in vitro functional assay. Such an assay will be critical for the development of PspA-containing vaccines. The other important findings relate to the locations and nature of the protection-eliciting epitopes of PspA. There are limited prior data on the locations of protection-eliciting PspA epitopes, but those data along with the data presented here make it clear that there is not a single epitope or domain of PspA that can elicit protective antibody and there exists at least one region of the αHD which seldom elicits protective antibody. Moreover, these data, in concert with prior data, strongly make the case that protective epitopes in the αHD are highly conformational (≥100-amino-acid fragments of the αHD are required), whereas at least some protection-eliciting epitopes in the proline-rich domain are encoded by ≤15-amino-acid sequences.

Diverse Mechanisms of Protective Anti-Pneumococcal Antibodies

“…This suggests that the complement deposition induced by these anti-PspA mAbs facilitates phagocytic uptake and killing by neutrophils (Kristian et al, 2016). In support of this observation, increased C3 deposition on the surface of bacteria via anti-PspA mAb binding has been demonstrated in numerous studies (Ren et al, 2004;Ren et al, 2012;Bitsaktsis et al, 2012;Goulart et al, 2013;Khan et al, 2015;Genschmer et al, 2019;Wiedinger et al, 2020). Additional functions for anti-PspA mAbs include inhibition of lactoferrin by anti-PspA mAbs (Bitsaktsis et al, 2012), and enhanced trapping and killing of S. pneumoniae by neutrophil extracellular traps (Martinez et al, 2019).…”