Influenza-Specific Antibody-Dependent Phagocytosis

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• Immunity to influenza A virus (IAV) is not fully understood.
• Non-neutralizing antibodies' role in reducing IAV disease severity is unclear.

Purpose of the Study:

• To investigate antibody-dependent phagocytosis (ADP) against diverse influenza hemagglutinin (HA) subtypes.
• To characterize ADP in healthy donors, IVIG, and following IAV infection in humans and macaques.

Main Methods:

• Measuring internalization of influenza protein-coated beads and live IAV into monocytic cells.
• Analyzing HA-specific ADP in human sera, IVIG, and animal models post-infection.

Main Results:

• Healthy adult sera and IVIG showed broad ADP against seasonal HA and weak cross-reactivity to non-circulating HA.
• ADP in infected macaques and humans facilitated phagocytosis of homologous and heterologous IAVs.
• Phagocytosed IAV exhibited reduced infectivity in vitro.

Conclusions:

• IAV infection induces influenza-specific ADP in humans and macaques, contributing to in vitro viral clearance.
• Repeated human IAV exposures likely generate cross-reactive ADP against novel strains.
• Further research into the protective potential of broadly reactive influenza-specific ADP is necessary.