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Fc receptor mediated activities by Env-specific human mAbs generated from volunteers receiving the DNA prime-protein boost HIV vaccine DP6-001.

Fc receptor mediated activities by Env-specific human mAbs generated from volunteers receiving the DNA prime-protein boost HIV vaccine DP6-001.
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Costa M, Pollara J, Edwards RW, Seaman M, Gorny MK, Montefiori D, Liao HX, Ferrari G, Lu S, Wang S,


Costa M, Pollara J, Edwards RW, Seaman M, Gorny MK, Montefiori D, Liao HX, Ferrari G, Lu S, Wang S, (click to view)

Costa M, Pollara J, Edwards RW, Seaman M, Gorny MK, Montefiori D, Liao HX, Ferrari G, Lu S, Wang S,

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Journal of virology 2016 9 14() pii

Abstract

HIV-1 is able to elicit broadly potent neutralizing antibodies in a very small subset of individuals only after several years’ infection and, therefore, vaccines that elicit these types of antibodies have been difficult to design. The RV144 trial showed that a moderate protection is possible, which may correlate with ADCC activity. Our previous studies demonstrated that in an HIV vaccine phase I trial, DP6-001, a polyvalent Env DNA prime-protein boost formulation, could elicit potent and broadly reactive, gp120-specific antibodies with positive neutralization activities. Here we report the production and analysis of HIV-1 Env-specific human monoclonal antibodies (mAbs) isolated from DP6-001 vaccinees. For this initial report, 13 mAbs from four DP6-001 vaccinees showed broad binding activities to gp120 proteins of diverse subtypes, both autologous and heterologous to vaccine immunogens. Equally cross-reactive Fc-mediated functional activities, including ADCC and ADCP, were present with both immune sera and isolated mAbs, confirming the induction of non-neutralizing functional mAbs by the DNA prime-protein boost vaccination. Elicitation of broadly reactive mAbs by vaccination in healthy human volunteers confirms the value of the polyvalent formulation in this HIV vaccine design.

IMPORTANCE
The roles of FcR mediated protective antibody responses are gaining more attention due their potential contribution to the low level protection against HIV-1 infection in RV144 trail. At the same time, the information from other HIV vaccine studies from humans is very limited. In the current report, both immune sera and monoclonal antibodies from vaccinated humans showed not only high level but also cross-subtype ADCC and ADCP activities using a polyvalent DNA prime-protein boost vaccine formulation.

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