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Polyfunctional Fc-effector profiles mediated by IgG subclass selection distinguish RV144 and VAX003 vaccines.

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The RV144 vaccine trial showed 31.2% efficacy against HIV infection, unlike the VAX003 trial. This protection was linked to specific antibody responses, not neutralizing antibodies, suggesting a new direction for HIV vaccine development.

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Area of Science:

  • Immunology
  • Vaccinology
  • Virology

Background:

  • The RV144 ALVAC-HIV vCP1521/AIDSVAX B/E vaccine trial in Thailand demonstrated modest efficacy against HIV.
  • The VAX003 trial, using only AIDSVAX B/E, did not confer protection, highlighting differences in vaccine regimens.

Purpose of the Study:

  • To investigate the immunological differences between the RV144 and VAX003 vaccine trials.
  • To understand the role of non-neutralizing antibodies and Fc-effector functions in HIV vaccine efficacy.

Main Methods:

  • Analysis of antibody subclass selection and Fc-mediated effector functions in participants of RV144 and VAX003 trials.
  • Characterization of antibody responses targeting the HIV envelope V2 loop.

Main Results:

  • The RV144 regimen induced coordinated Fc-mediated responses via selective induction of immunoglobulin G3 (IgG3).
  • VAX003 elicited monofunctional antibody responses, influenced by IgG4 selection due to protein boosts.
  • RV144 uniquely induced IgG1 and IgG3 antibodies targeting the HIV envelope V2 loop crown.

Conclusions:

  • Differences in vaccine efficacy may stem from subclass selection of antibodies and coordinated humoral functional responses.
  • Targeting strain-specific V2 loop epitopes with specific antibody subclasses could be crucial for effective HIV vaccine design.