Profiles of human serum antibody responses elicited by three leading HIV vaccines focusing on the induction of Env-specific antibodies.

Michael Vaine,James Arthos,David Montefiori,Qin Liu,Paul Goepfert,Shan Lu,Shixia Wang,M Juliana Mcelrath,Cheryl A Stoddart

doi:10.1371/journal.pone.0013916

Abstract

In the current report, we compared the specificities of antibody responses in sera from volunteers enrolled in three US NIH-supported HIV vaccine trials using different immunization regimens. HIV-1 Env-specific binding antibody, neutralizing antibody, antibody-dependent cell-mediated cytotoxicity (ADCC), and profiles of antibody specificity were analyzed for human immune sera collected from vaccinees enrolled in the NIH HIV Vaccine Trial Network (HVTN) Study #041 (recombinant protein alone), HVTN Study #203 (poxviral vector prime-protein boost), and the DP6-001 study (DNA prime-protein boost). Vaccinees from HVTN Study #041 had the highest neutralizing antibody activities against the sensitive virus along with the highest binding antibody responses, particularly those directed toward the V3 loop. DP6-001 sera showed a higher frequency of positive neutralizing antibody activities against more resistant viral isolate with a significantly higher CD4 binding site (CD4bs) antibody response compared to both HVTN studies #041 and #203. No differences were found in CD4-induced (CD4i) antibody responses, ADCC activity, or complement activation by Env-specific antibody among these sera. Given recent renewed interest in realizing the importance of antibody responses for next generation HIV vaccine development, different antibody profiles shown in the current report, based on the analysis of a wide range of antibody parameters, provide critical biomarker information for the selection of HIV vaccines for more advanced human studies and, in particular, those that can elicit antibodies targeting conformational-sensitive and functionally conserved epitopes.

Highlights

Developing a safe and effective vaccine to control the global transmission of Human Immunodeficiency Virus Type 1 (HIV-1) remains one of the greatest challenges
In-depth analysis of antibody responses elicited in RV144 trial volunteers requires baseline information on the qualities of human anti-Env antibody responses elicited by other types of HIV-1 vaccines
All three candidate HIV vaccines included in the current analysis were designed to elicit HIV-1 Env-specific antibody responses (Table 1)

Summary

Introduction

Developing a safe and effective vaccine to control the global transmission of Human Immunodeficiency Virus Type 1 (HIV-1) remains one of the greatest challenges. Recently completed Phase III human HIV-1 vaccine trial, RV144, using a canarypox vector prime-recombinant envelope (Env) protein boost design, showed a low but significant 31% reduction of infection compared with placebo [11]. The mechanism for such protection in RV144 is unknown but protective antibody is suspected to play a key role. In-depth analysis of antibody responses elicited in RV144 trial volunteers requires baseline information on the qualities of human anti-Env antibody responses elicited by other types of HIV-1 vaccines. Several new vaccination approaches have significantly improved the magnitude or quality of HIV-1 Env-specific antibody responses in humans and, provide the opportunity to compare the unique profiles of antibody responses elicited by different HIV vaccine strategies

Methods

Results

Conclusion