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dc.contributor.authorCosta, Matthew R.
dc.contributor.authorPollara, Justin
dc.contributor.authorEdwards, Regina Whitney
dc.contributor.authorSeaman, Michael S.
dc.contributor.authorGorny, Miroslaw K.
dc.contributor.authorMontefiori, David C.
dc.contributor.authorLiao, Hua-Xin
dc.contributor.authorFerrari, Guido
dc.contributor.authorLu, Shan
dc.contributor.authorWang, Shixia
dc.date2022-08-11T08:08:56.000
dc.date.accessioned2022-08-23T16:12:53Z
dc.date.available2022-08-23T16:12:53Z
dc.date.issued2016-10-28
dc.date.submitted2017-09-06
dc.identifier.citation<p>J Virol. 2016 Oct 28;90(22):10362-10378. Print 2016 Nov 15. <a href="https://doi.org/10.1128/JVI.01458-16">Link to article on publisher's site</a></p>
dc.identifier.issn0022-538X (Linking)
dc.identifier.doi10.1128/JVI.01458-16
dc.identifier.pmid27630232
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33493
dc.description.abstractHIV-1 is able to elicit broadly potent neutralizing antibodies in a very small subset of individuals only after several years of infection, and therefore, vaccines that elicit these types of antibodies have been difficult to design. The RV144 trial showed that moderate protection is possible and that this protection may correlate with antibody-dependent cellular cytotoxicity (ADCC) activity. Our previous studies demonstrated that in an HIV vaccine phase I trial, the DP6-001 trial, a polyvalent Env DNA prime-protein boost formulation could elicit potent and broadly reactive, gp120-specific antibodies with positive neutralization activities. Here we report on the production and analysis of HIV-1 Env-specific human monoclonal antibodies (hMAbs) isolated from vaccinees in the DP6-001 trial. For this initial report, 13 hMAbs from four vaccinees in the DP6-001 trial showed broad binding to gp120 proteins of diverse subtypes both autologous and heterologous to vaccine immunogens. Equally cross-reactive Fc receptor-mediated functional activities, including ADCC and antibody-dependent cellular phagocytosis (ADCP) activities, were present with both immune sera and isolated MAbs, confirming the induction of nonneutralizing functional hMAbs by the DNA prime-protein boost vaccination. Elicitation of broadly reactive hMAbs by vaccination in healthy human volunteers confirms the value of the polyvalent formulation in this HIV vaccine design. IMPORTANCE: The roles of Fc receptor-mediated protective antibody responses are gaining more attention due to their potential contribution to the low-level protection against HIV-1 infection that they provided in the RV144 trial. At the same time, information about hMabs from other human HIV vaccine studies is very limited. In the current study, both immune sera and monoclonal antibodies from vaccinated humans showed not only high-level ADCC and ADCP activities but also cross-subtype ADCC and ADCP activities when a polyvalent DNA prime-protein boost vaccine formulation was used.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=27630232&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsPublisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.
dc.subjectImmunology and Infectious Disease
dc.subjectVirology
dc.titleFc Receptor-Mediated Activities of Env-Specific Human Monoclonal Antibodies Generated from Volunteers Receiving the DNA Prime-Protein Boost HIV Vaccine DP6-001
dc.typeJournal Article
dc.source.journaltitleJournal of virology
dc.source.volume90
dc.source.issue22
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3041&amp;context=gsbs_sp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/2018
dc.identifier.contextkey10714521
refterms.dateFOA2022-08-23T16:12:54Z
html.description.abstract<p>HIV-1 is able to elicit broadly potent neutralizing antibodies in a very small subset of individuals only after several years of infection, and therefore, vaccines that elicit these types of antibodies have been difficult to design. The RV144 trial showed that moderate protection is possible and that this protection may correlate with antibody-dependent cellular cytotoxicity (ADCC) activity. Our previous studies demonstrated that in an HIV vaccine phase I trial, the DP6-001 trial, a polyvalent Env DNA prime-protein boost formulation could elicit potent and broadly reactive, gp120-specific antibodies with positive neutralization activities. Here we report on the production and analysis of HIV-1 Env-specific human monoclonal antibodies (hMAbs) isolated from vaccinees in the DP6-001 trial. For this initial report, 13 hMAbs from four vaccinees in the DP6-001 trial showed broad binding to gp120 proteins of diverse subtypes both autologous and heterologous to vaccine immunogens. Equally cross-reactive Fc receptor-mediated functional activities, including ADCC and antibody-dependent cellular phagocytosis (ADCP) activities, were present with both immune sera and isolated MAbs, confirming the induction of nonneutralizing functional hMAbs by the DNA prime-protein boost vaccination. Elicitation of broadly reactive hMAbs by vaccination in healthy human volunteers confirms the value of the polyvalent formulation in this HIV vaccine design.</p> <p>IMPORTANCE: The roles of Fc receptor-mediated protective antibody responses are gaining more attention due to their potential contribution to the low-level protection against HIV-1 infection that they provided in the RV144 trial. At the same time, information about hMabs from other human HIV vaccine studies is very limited. In the current study, both immune sera and monoclonal antibodies from vaccinated humans showed not only high-level ADCC and ADCP activities but also cross-subtype ADCC and ADCP activities when a polyvalent DNA prime-protein boost vaccine formulation was used.</p>
dc.identifier.submissionpathgsbs_sp/2018
dc.contributor.departmentDepartment of Medicine
dc.source.pages10362-10378
dc.contributor.studentMatthew R. Costa


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