Multiantibody Strategies for HIV

Abstract

Vaccination strategies depend entirely on the appropriate responsiveness of our immune system against particular antigens. For this active immunization to be truly effective, neutralizing antibodies (nAbs) need to efficiently counter the infectivity or propagation of the pathogen. Some viruses, including HIV, are able to take advantage of this immune response in order to evade nAbs. This review focuses on viral immune evasion strategies that result directly from a robust immune response to infection or vaccination. A rationale for multi-Ab therapy to circumvent this phenomenon is discussed. Progress in the formulation, production, and regulatory approval of monoclonal antibodies (mAbs) is presented.

Pharmacokinetics and Preliminary Safety of Pod-Intravaginal Rings Delivering the Monoclonal Antibody VRC01-N for HIV Prophylaxis in a Macaque Model

“…A subset of bNAbs, including VRC01, has been shown to block HIV-1 transmission by cell-associated virus (57). Two vaginal gel formulations have both completed phase 1 clinical trials: the Mabgel triple combination of 2F5, 2G12, and 4E10 (25) and 2G12 manufactured in a Nicotiana-based process (26). A phase 1 clinical trial to assess the safety of a vaginal film containing VRC01-N is ongoing (58).…”

“…Intravenously delivered 2G12 (21) and 2F5 and 4E10 (21,22), as well as topically applied b12 (23,24), protected against simian-human immunodeficiency virus (SHIV) infection in challenge studies using rhesus and cynomolgus macaques. Both vaginal gel formulations of a triple MAb combination of 2F5, 2G12, and 4E10 (Mabgel) (25) and 2G12 manufactured in a Nicotiana-based process (26) have completed phase 1 clinical trials.…”

Antibody-based concepts for multipurpose prevention technologies

“…Many of the new monoclonal antibodies against HIV (PGT121-PGT128) are almost 10-fold more potent than the recently described PG9, PG16 and VRC01, and 100-fold more potent that the original prototype HIV neutralizing antibodies (b12, 2G12, 4E10) (Walker et al, 2011; Hiatt et al, 2013). Analysis of the anti-HIV broadly neutralizing monoclonal antibodies (bnAbs) now available suggests that certain combinations of potent antibodies have superior coverage of the enormous diversity of global circulating viruses and should be sought in active or passive immunization regimes.…”

Filovirus Neutralising Antibodies: Mechanisms of Action and Therapeutic Application

“…A major drawback of mAbs is that they are specific to one epitope. Consequently, they are more vulnerable to immune escape from rapidly mutating viruses, and this has been observed with many other viruses such as influenza, HIV or SARS-CoV-2 [ 77 , 152 , 153 , 154 , 155 ]. In an experimental setting, Steeds et al showed that GP variants G74R, P330S and H407Y were capable of readily escaping the WHO research neutralisation standard KZ52.…”