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

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dc.contributorLab. Bacteriologiapt_BR
dc.contributor.authorGenschmer, Kristopher R.pt_BR
dc.contributor.authorVadesilho, Cintia Fiuza Marquespt_BR
dc.contributor.authorMcDaniel, Larry S.pt_BR
dc.contributor.authorPark, Sang-Sangpt_BR
dc.contributor.authorHale, Yvettept_BR
dc.contributor.authorMiyaji, Eliane Namiept_BR
dc.contributor.authorBriles, David E.pt_BR
dc.date.accessioned2020-07-09T21:25:46Z-
dc.date.available2020-07-09T21:25:46Z-
dc.date.issued2019pt_BR
dc.identifier.citationGenschmer KR., Vadesilho CFM, McDaniel LS., Park S-S, Hale Y, Miyaji EN, et al. The modified surface killing assay distinguishes between protective and nonprotective antibodies to PspA. mSphere. 2019 Dec;4(6):e00589-19. doi:10.1128/mSphere.00589-19.pt_BR
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/2880-
dc.description.abstractPneumococcal 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 proline-rich domain of PspA. Two of the other most protective MAbs and the weakly protective MAb reacted with a fragment from PspA’s a-helical domain (aHD), containing amino acids (aa) 148 to 247 from the N terminus of PspA. The fourth highly protective MAb recognized none of the overlapping 81- or 100-aa fragments of PspA. The two nonprotective MAbs recognized a more N-terminal aHD fragment (aa 48 to 147). IMPORTANCE 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 aHD which seldom elicits protective antibody. Moreover, these data, in concert with prior data, strongly make the case that protective epitopes in the aHD are highly conformational (=100-amino-acid fragments of the aHD are required), whereas at least some protection-eliciting epitopes in the proline-rich domain are encoded by =15-amino-acid sequences.pt_BR
dc.description.sponsorship(NIH) National Institutes of Healthpt_BR
dc.description.sponsorship(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulopt_BR
dc.format.extente00589-19pt_BR
dc.language.isoEnglishpt_BR
dc.relation.ispartofmSpherept_BR
dc.rightsOpen accesspt_BR
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/pt_BR
dc.titleThe modified surface killing assay distinguishes between protective and nonprotective antibodies to PspApt_BR
dc.typeArticlept_BR
dc.rights.licenseCC BYpt_BR
dc.identifier.doi10.1128/mSphere.00589-19pt_BR
dc.identifier.urlhttps://doi.org/10.1128/mSphere.00589-19pt_BR
dc.contributor.external(UAB) University of Alabama at Birminghampt_BR
dc.contributor.externalUniversity of Mississippi Medical Centerpt_BR
dc.identifier.citationvolume4pt_BR
dc.identifier.citationissue6pt_BR
dc.subject.keywordPspApt_BR
dc.subject.keywordmodified surface killing assaypt_BR
dc.subject.keywordpneumococcal surface protein Apt_BR
dc.relation.ispartofabbreviatedmSpherept_BR
dc.identifier.citationabntv. 4, n. 6, p. e00589-19, dec. 2019pt_BR
dc.identifier.citationvancouver2019 Dec;4(6):e00589-19pt_BR
dc.contributor.butantanVadesilho, Cintia Fiuza Marques|:Aluno|:Lab. Bacteriologia|:pt_BR
dc.contributor.butantanMiyaji, Eliane Namie|:Pesquisador|:Lab. Bacteriologia|:pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2011/13671-5pt_BR
dc.sponsorship.butantanNational Institutes of Health (NIH)¦¦R01AI021548pt_BR
dc.sponsorship.butantanNational Institutes of Health (NIH)¦¦R01AI118805pt_BR
dc.sponsorship.butantanNational Institutes of Health (NIH)¦¦R01 DC006452pt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
dc.description.dbindexedYespt_BR
item.fulltextCom Texto completo-
item.languageiso639-1English-
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item.openairetypeArticle-
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