Immune Complex Vaccine Strategies to Combat HIV-1 and Other Infectious Diseases—Tang 2021

Immune complexes (ICs) comprising antibody-bound antigens have immunomodulatory properties that can improve vaccine effectiveness. Fc fragments of antibody components engage Fc receptors, complement, and complement receptors on immune cells to modulate ICs. Fc-mediated actions help innate and adaptive immune systems interact to affect adaptive response quality and quantity. The Fab fragment immunoregulates in addition to Fc. The Fab fragment's high-affinity antigen-binding regions sterically occlude their specific epitopes from other antibodies. Fab-mediated binding also causes allosteric changes at close or distant antigenic sites. We examine published studies to show how ICs' immunomodulatory properties have been investigated or used in a vaccination strategy to fight a variety of infectious diseases, including HIV-1. We highlight IC vaccine candidates that use Fab-mediated steric and allosteric effects to guide antibody responses away or toward the V1V2 domain, V3 loop, and other antigenic regions on the HIV-1 envelope gp120 glycoprotein. IC-based HIV-1 vaccines, like other approaches, face major obstacles before reaching the clinic, but studies of this vaccine strategy have revealed antibodies' multifaceted activities beyond their host defense against HIV-1 and other microbial pathogens.

Tang, A. F., Enyindah-Asonye, G., & Hioe, C. E. (2021). Immune Complex Vaccine Strategies to Combat HIV-1 and Other Infectious Diseases. Vaccines, 9(2), 112. https://doi.org/10.3390/vaccines9020112