Broad Neutralizing Antibodies to HIV Env and Other Complex Viral Antigens from Vaccinated Cows

Abstract

The idea of using antibodies to restrain HIV viral replication has been a growing interest since many years ago. HIV-patient serum with elite virus-neutralizing breadth has led to the preparation of broadly neutralizing antibodies (BrNAbs) with long and highly mutated CDRH3 domains that can neutralize a broad array of viral strains and prevent transmission in animal models. Recent advances have resulted in the discovery of BrNAbs that are more potent and can neutralize many HIV-1 subtypes. However, elicitation of these antibodies in infected individuals usually requires a long time of antigen exposure. Though BrNAbs are shown to be successful either therapeutically or prophylactically against HIV-1, production of these antibodies in bulk, commercial-sized batches are expensive and non-affordable particularly for poor countries. Therefore, more durable preventative or therapeutic strategies are required. Immunization of the cows with HIV Env is shown to be capable of producing 20 kg purified anti-HIV-1 BrNAbs and this amount could be sufficient for 2 million × 10 mg doses for formulation and pre-clinical testing as an HIV microbicide. In addition, bovine immunoglobulins typically have variable third heavy complementarity determining regions (CDRH3) that may potentially facilitate access to antigenic epitopes that are very difficult for other species to engage. Thus, cows could be engaged to elicit anti-HIV antibodies with the features of human BrNAbs and bovine colostrum could be a promising and cheap resource for the development of combination microbicides.

Bovine-Origin Human Therapy; Need More Attention

“…immunity to human disease [7][8][9][10][11][12] . Bovine colostrum may be beneficial in people infected with HIV 13 , where IgG derived from colostrum enhances immune response to HIV. Antibodies from some leukemic cattle can inhibit HIV-1 reverse transcriptase activity in vitro 14 .…”

“…Bovine vaccination with a specific human virus results in production of antigen-specific antibodies in sera and colostrum (Hyperimmune milk) of bovine 13 .Bovine yields remarkably high BrNAbs titers rather than other animal species after vaccination. Indeed, bovine antibodies from vaccinated cows could ultimately benefit for individuals infected with HIV through their extraordinary characteristics.…”

“…Bovine could be used in the biological production of human polyclonal antibodies where transgenic calves and transgenic platforms were created to produce polyclonal antibodies derived from animals and human sequences 34,35 . Coping with the problem of that most polyclonal antibodies will target non-neutralizing epitopes 13 , through producing monoclonal BrNAbs targeting preserved epitopes among different subtypes of viruses with humanization of bovine monoclonal antibody 36 reducing antiantibody responses 37 .…”

Reprogramming the antigen specificity of B cells using genome-editing technologies

“…We wanted to add these features into the repertoire directly by modifying BCRs using genome-editing technologies. The existence of antibodies with protective paratopes encoded mostly within their HCs (Heydarchi et al, 2016;Lee et al, 2017;Sok et al, 2017;Sui et al, 2009) suggested that it might be possible to achieve this goal through replacement of the recombined HC variable region alone. In order for engineered HCs to then function as desired, they must pair with endogenous LCs and retain their ability to recognize antigen as chimeric cell surface-expressed BCRs (Feige et al, 2010).…”