Broadly Neutralizing Bovine Antibodies: Highly Effective New Tools against Evasive Pathogens?
Matthew J BurkePeter G StockleyJoan BoyesPublished in: Viruses (2020)
Potent antibody-mediated neutralization is critical for an organism to combat the vast array of pathogens it will face during its lifetime. Due to the potential genetic diversity of some viruses, such as HIV-1 and influenza, standard neutralizing antibodies are often ineffective or easily evaded as their targets are masked or rapidly mutated. This has thwarted efforts to both prevent and treat HIV-1 infections and means that entirely new formulations are required to vaccinate against influenza each year. However, some rare antibodies isolated from infected individuals confer broad and potent neutralization. A subset of these broadly neutralizing antibodies possesses a long complementarity-determining 3 region of the immunoglobulin heavy chain (CDR H3). This feature generates unique antigen binding site configurations that can engage conserved but otherwise inaccessible epitope targets thus neutralizing many viral variants. Remarkably, ultralong CDR H3s are a common feature of the cow antibody repertoire and are encoded by a single variable, diversity, joining (VDJ) recombination that is extensively diversified prior to antigen exposure. Recently, it was shown that cows rapidly generate a broadly neutralizing response upon exposure to HIV-1 and this is primarily mediated by these novel ultralong antibody types. This review summarises the current knowledge of these unusual CDR H3 structures and discusses their known and potential future uses.
Keyphrases
- dengue virus
- antiretroviral therapy
- hiv positive
- hiv infected
- hiv testing
- genetic diversity
- human immunodeficiency virus
- hepatitis c virus
- hiv aids
- men who have sex with men
- zika virus
- gram negative
- machine learning
- healthcare
- high resolution
- deep learning
- south africa
- multidrug resistant
- antimicrobial resistance
- sars cov
- dna damage
- high density
- quality improvement
- dna methylation
- high throughput sequencing