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ST109 Antigenic specificity and neutralizing activity of antibody responses elicited by different gp120/mAb immune complex vaccines

Kumar Rajnish; Tuen, Michael; Hioe, Catarina
JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2013
doi: 10.1097/01.qai.0000429271.36210.4f
Abstracts: PDF Only

HIV-1 envelope gp120 antigen is an important target for neutralizing antibody (NAb) responses against the virus. However, constructing gp120-based vaccines that elicit potent and broad NAbs has proven to be a formidable challenge. Previously, enhanced immunogenicity of gp120 and especially its V3 epitopes was observed when gp120 was administered as immune complex vaccines with monoclonal antibodies (mAbs) specific for the CD4bs. In this study, we compared antibody (Ab) responses generated by immunization with gp120 complexed with mAbs specific for CD4-binding site (CD4bs), C2, V3, and V2. The gp120/CD4bs complex induced high level and high avidity of anti-gp120 Abs. Cross-reactive anti-V3 NAbs were generated and were effective against a panel of heterologous Tier 1 subtype B HIV-1 isolates. The gp120/V2 complex also elicits anti-V3 Nabs, albeit at lower titer and avidity. The gp120/C2 complex elicited gp120-binding Abs that were not against V3 and had no neutralizing activity, whereas the gp120/V3 complex was less immunogenic than uncomplexed gp120. These results demonstrate the capacity of immune complexes to modulate Ab responses and this activity is dependent on the fine specificity of Abs used to form the complexes. Moreover, we observed that the superior immunogenicity of the gp120/CD4bs complex correlated with stable high-affinity complex formation and enhanced resistance of V3 and other Ab epitopes from proteolysis. Immune complexes offer a promising vaccine platform for Ab-based HIV vaccine; however, further development is needed to achieve broader Nab response including the targeting of other gp120 epitopes and the utilization of a cocktail of gp120/mAb complexes in a prime/boost protocol.

© 2013 Lippincott Williams & Wilkins, Inc.