Hioe et al.
Jan 5, 2022
This study explores the potential of non-neutralizing antibodies targeting HIV-1 envelope regions (V1V2 and V3) to reduce mucosal infection and virus burden in humanized mice.
This study explores the potential of non-neutralizing antibodies targeting HIV-1 envelope regions (V1V2 and V3) to reduce mucosal infection and virus burden in humanized mice. The research aimed to assess the antiviral activity of monoclonal antibodies (mAbs) 2158 (anti-V1V2) and 2219 (anti-V3), which have poor neutralizing activity but bind to immunogenic sites on the virus envelope.
Key findings:
Virus Control: Neither mAb fully prevented infection, but treatment with mAb 2219 significantly reduced plasma vRNA and viral load in tissues, particularly in the spleen. In contrast, mAb 2158 had minimal impact on viral burden.
Fc Functions: mAb 2219 demonstrated stronger Fc-mediated functions, including antibody-dependent cellular phagocytosis (ADCP) and complement activation, contributing to viral suppression. This was confirmed by introducing mutations to the Fc region of 2219, which diminished its efficacy.
Mechanism of Action: The study highlighted the importance of non-neutralizing Fc-dependent mechanisms (like ADCP and complement activation) in controlling HIV-1, especially when neutralizing activity is weak. These results suggest that non-neutralizing antibodies may still play a role in limiting HIV-1 replication and viral burden.
Overall, the study provides evidence for the antiviral potential of non-neutralizing antibodies and emphasizes the importance of Fc-dependent functions in controlling HIV-1 infection. This could inform the development of future vaccine strategies leveraging these immune functions.
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010183