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Polyfunctionality and breadth of HIV-1 antibodies are associated with delayed disease progression
Marloes Grobben1,2, Margreet Bakker1,2, Angela I Schriek1,2
1Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Amsterdam, The Netherlands.
Plos Pathogens
|December 11, 2024
Summary
Broad, polyfunctional antibodies, particularly IgG1, are linked to slower HIV-1 disease progression. This finding offers new insights for developing effective antibody-based HIV therapies and potential cures.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- HIV-1 infection necessitates lifelong treatment, driving the search for cures and vaccines.
- Antibody effector functions are crucial in combating HIV-1, but their specific beneficial properties remain unclear.
- Understanding antibody features associated with delayed disease progression is vital for therapeutic development.
Purpose of the Study:
- To identify specific antibody features correlating with delayed disease progression in untreated HIV-1 infection.
- To investigate the association between antibody polyfunctionality and HIV-1 disease course.
Main Methods:
- Serum samples from untreated individuals in the Amsterdam Cohort Studies were analyzed at 6 months and 3 years post-seroconversion (post-SC).
- A Luminex antibody Fc array profiled 15 Fc features against 20 HIV-1 envelope glycoprotein antigens.
- Data on Fc features were compared with neutralization breadth and disease progression markers.
Main Results:
- Higher HIV-1 specific IgG1 and lower IgG2/IgG4 levels at 3 years post-SC were associated with delayed progression.
- Delayed disease progression correlated with broad and polyfunctional antibody responses.
- Antibody interaction with Fc γ receptors (FcγRs), especially FcγRIIa, and C1q positively correlated with delayed progression.
- Antibody Fc features strongly correlated with neutralization breadth.
Conclusions:
- Broad, polyfunctional antibodies are strongly associated with delayed HIV-1 disease progression.
- Specific antibody Fc features, including IgG1 levels and FcγR interactions, are key indicators of slower disease advancement.
- These findings support the development of novel antibody-based strategies for HIV-1 therapy and cure.
