The COVID-19 pandemic has made the development of novel vaccines a high priority for public health. While many vaccines have focused on the generation of neutralizing antibodies, we have discovered a novel herpes simplex virus (HSV) vaccine candidate, designated ΔgD-2, that can preferentially elicit non-neutralizing antibodies that function through Fcγ receptor (FcγR) activation and thus effector function of antibodies. In particular, the ΔgD-2 vector elicits FcγRIV-activating antibodies of the IgG2c isotype, which are associated with antibody-dependent cellular cytotoxicity (ADCC). The recent paper by Kaugars et al. 2021, demonstrates that a strain of ΔgD-2 expressing the hemagglutinin (HA) protein from influenza, designated ΔgD-2::HAPR8, can be used as a vaccine vector to protect against both influenza and HSV. In immunized sera, ΔgD-2::HAPR8 elicits high levels of anti-HA FcγRIV-activating IgG2c antibodies. Based on recent studies with the ΔgD-2 vector and its interaction with dendritic cells, we hypothesize that the vaccine works by promoting dendritic cell survival, allowing these cells to potently activate helper T cells, and ultimately leading to the immunoglobulin class switch in B cells. In this article, we discuss lessons from analyzing the ΔgD-2 vectors to elucidate antibody-dependent cellular killing. This work highlights the importance of combining antibody effector function and neutralization for optimal protective vaccine-induced immune responses.
Cancer immunology, Clinical immunology, Immunochemistry