Incorporating the cluster a and v1v2 targets into a minimal structural unit of the hiv-1 envelope to elicit a cross-clade response with potent fc-effector functions

Rebekah Sherburn, William D. Tolbert, Suneetha Gottumukkala, Andrew P. Hederman, Guillaume Beaudoin-Bussières, Sherry Stanfield-Oakley, Marina Tuyishime, Guido Ferrari, Andrés Finzi, Margaret E. Ackerman, Marzena Pazgier*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


The generation of a potent vaccine for the prevention and/or control of HIV-1 has been unsuccessful to date, despite decades of research. Existing evidence from both infected individuals and clinical trials support a role for non-neutralizing or weakly neutralizing antibodies with potent Fc-effector functions in the prevention and control of HIV-1 infection. Vaccination strategies that induce such antibodies have proven partially successful in preventing HIV-1 infection. This is largely thought to be due to the polyclonal response that is induced in a vaccine setting, as opposed to the infusion of a single therapeutic antibody, which is capable of diverse Fc-effector functions and targets multiple but highly conserved epitopes. Here, we build on the success of our inner domain antigen, ID2, which incorporates conformational CD4-inducible (CD4i) epitopes of constant region 1 and 2 (C1C2 or Cluster A), in the absence of neutralizing antibody epitopes, into a minimal structural unit of gp120. ID2 has been shown to induce Cluster A-specific antibodies in a BALB/c mouse model with Fc-effector functions against CD4i targets. In order to generate an immunogen that incorporates both epitope targets implicated in the protective Fc-effector functions of antibodies from the only partially successful human vaccine trial, RV144, we incorporated the V1V2 domain into our ID2 antigen generating ID2-V1V2, which we used to immunize in combination with ID2. Immunized BALB/c mice generated both Cluster A-and V1V2-specific antibodies, which synergized to significantly improve the Fc-mediated effector functions compared to mice immunized with ID2 alone. The sera were able to mediate both antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). We therefore conclude that ID2-V1V2 + ID2 represents a promising vaccine immunogen candidate for the induction of antibodies with optimal Fc-mediated effector functions against HIV-1.

Original languageEnglish
Article number975
Issue number9
StatePublished - Sep 2021
Externally publishedYes


  • ADCC
  • ADCP
  • Fc-effector functions
  • HIV-1
  • ID2
  • ID2-V1V2
  • Vaccines


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