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    Fc Receptor-Mediated Activities of Env-Specific Human Monoclonal Antibodies Generated from Volunteers Receiving the DNA Prime-Protein Boost HIV Vaccine DP6-001

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    Authors
    Costa, Matthew R.
    Pollara, Justin
    Edwards, Regina Whitney
    Seaman, Michael S.
    Gorny, Miroslaw K.
    Montefiori, David C.
    Liao, Hua-Xin
    Ferrari, Guido
    Lu, Shan
    Wang, Shixia
    Student Authors
    Matthew R. Costa
    UMass Chan Affiliations
    Department of Medicine
    Document Type
    Journal Article
    Publication Date
    2016-10-28
    Keywords
    Immunology and Infectious Disease
    Virology
    
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    Abstract
    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. 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.
    Source

    J Virol. 2016 Oct 28;90(22):10362-10378. Print 2016 Nov 15. Link to article on publisher's site

    DOI
    10.1128/JVI.01458-16
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/33493
    PubMed ID
    27630232
    Related Resources

    Link to Article in PubMed

    Rights
    Publisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.
    ae974a485f413a2113503eed53cd6c53
    10.1128/JVI.01458-16
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