Antibody class-switching as a strategy to improve HIV-1 neutralization. Issue 11 (November 2022)

• Record Type: Journal Article
• Authors: Scheepers, Cathrine; Richardson, Simone I.; Moyo-Gwete, Thandeka; Moore, Penny L.
• Is Part Of: Trends in molecular medicine. Volume 28:Issue 11(2022)
• Page Start: 979
• Page End: 988
• Publication Date: 2022-11
• Subjects: neutralization -- IgG3 hinge -- IgA CH1 -- class-switching -- isotype -- HIV-1 vaccine design; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; Physiology, Pathological -- Periodicals; 572.8
• DOI: 10.1016/j.molmed.2022.08.010
• Languages: English
• ISSNs: 1471-4914

Abstract

Abstract : Broadly neutralizing antibodies (bNAbs), when administered through passive immunization, are protective against HIV-1 infection. Current HIV-1 vaccine strategies are aimed at guiding the immune system to make bNAbs by mimicking their development during infection. Somatic hypermutation of the variable region is known to be crucial for the development of bNAbs. More recently, however, studies have shown how class-switch recombination (CSR) resulting in the generation of different antibody isotypes may serve as an additional mechanism through which antibodies can gain neutralization breadth and potency. In this review, we discuss the importance of different antibody isotypes for HIV-1 neutralization breadth and potency and how this information can be leveraged to improve passive and active immunization against HIV-1. Highlights: Class-switch recombination (CSR), which involves maintaining the antigen-binding variable region and swapping out the constant region of antibodies, enables diversity in immune responses to disease. Antibody isotype diversity is associated with increased neutralization breadth towards pathogens such as HIV-1. The constant region of antibodies, previously thought to only mediate Fc effector function, can also influence the neutralization breadth and potency of HIV-1-directed antibodies. Within HIV-1 directed antibody lineages, CSR represents another mechanism through which antibodies can counter viral immune escape. Antibody IgG3 and IgA1 isotypes mediate enhanced function through different mechanisms. IgG3 relies on increased flexibility, while IgA1 depends on conformational changes within the paratope.