title: Conformational Masking and Receptor-Dependent Unmasking of Highly Conserved Env Epitopes Recognized by Non-Neutralizing Antibodies That Mediate Potent ADCC against HIV-1.
abstract: The mechanism of antibody-mediated protection is a major focus of HIV-1 vaccine development and a significant issue in the control of viremia. Virus neutralization, Fc-mediated effector function, or both, are major mechanisms of antibody-mediated protection against HIV-1, although other mechanisms, such as virus aggregation, are known. The interplay between virus neutralization and Fc-mediated effector function in protection against HIV-1 is complex and only partially understood. Passive immunization studies using potent broadly neutralizing antibodies (bnAbs) show that both neutralization and Fc-mediated effector function provides the widest dynamic range of protection; however, a vaccine to elicit these responses remains elusive. By contrast, active immunization studies in both humans and non-human primates using HIV-1 vaccine candidates suggest that weakly neutralizing or non-neutralizing antibodies can protect by Fc-mediated effector function, albeit with a much lower dynamic range seen for passive immunization with bnAbs. HIV-1 has evolved mechanisms to evade each type of antibody-mediated protection that must be countered by a successful AIDS vaccine. Overcoming the hurdles required to elicit bnAbs has become a major focus of HIV-1 vaccine development. Here, we discuss a less studied problem, the structural basis of protection (and its evasion) by antibodies that protect only by potent Fc-mediated effector function.
authors.affiliation: Division of Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA. glewis@ihv.umaryland.edu.
authors.forename: George K
authors.initials: GK
authors.lastname: Lewis
authors.affiliation: Centre de Recherche du CHUM, Department of Microbiology, Infectiology, and Immunology, Université de Montréal, Montreal, QC H2X 0A9, Canada. andres.finzi@umontreal.ca.
authors.forename: Andrés
authors.initials: A
authors.lastname: Finzi
authors.affiliation: Division of Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA. adevico@umaryland.edu.
authors.forename: Anthony L
authors.initials: AL
authors.lastname: DeVico
authors.affiliation: Division of Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA. mpazgier@umaryland.edu.
authors.forename: Marzena
authors.initials: M
authors.lastname: Pazgier
mesh_terms: D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D000939:Epitopes / Q000276:immunology*; D015483:HIV Antibodies / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D011323:Primates; D011487:Protein Conformation; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000276:immunology*
chemical_list: D000939:Epitopes; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus
keywords: AIDS; Fc; HIV-1; antibody; effector-function; protection; vaccine