The Role of Viral Immunology in Development of Vaccines and Immunotherapy for HIV Herpesviruses and COVID-19

Professor Anthony (Tony) Cunningham, AO, FAHMS, MD, FRACP, FRCPA is an infectious diseases physician, clinical virologist and scientist, well known internationally for his research on the immunobiology of HIV and herpesviruses, his work on vaccine development and trialling, especially for shingles and herpes, and as an antivirals expert. He has served on numerous international expert panels on HIV/HSV, antivirals and vaccines and is Director, Centre for Virus Research at The Westmead Institute for Medical Research; Director, Australian Centre for HIV and Hepatitis Virology Research and Professor in the Faculty of Medicine and Health at the University of Sydney.

Abstract: Recombinant Zoster vaccine (RZV) has recently been developed as a highly efficacious vaccine for Herpes zoster, especially in the ageing, yet there is still no vaccine for HIV or Herpes simplex virus (HSV). Immunologic studies can assist in developing vaccines in several ways:

1. Understanding the mechanism of action of successful vaccines like RZV to apply to HSV.
2. Understanding the initial interactions of the immune system with these viruses and how this can inform stimulation of these initial defences with vaccines.

We have developed and used human explant systems to explore both of these fields. Lymph node explants are being used to define the mechanism of action the adjuvants responsible for the remarkable efficacy of RZV. Anogenital mucosal explants are being used to examine the entry of HIV and HSV and their interactions with dendritic cells in the epidermis and other immune cells in the dermis. Surprisingly, the latter studies have defined a new epidermal dendritic cell which more readily takes up HIV and HSV than Langerhans cells (Bertram et al Nat Comms 2019; Bertram/Truong et al PloS Pathogens 2021). Both cell types mediate transfer of virus or antigen to other immune cells with different outcomes for the immune system. Furthermore, HIV blocks interferon production in its mucosal target cells but this is counteracted in novel ways by early infiltration of interferon alpha secreting plasmacytoid dendritic cells (Tong et al PloS Pathogens 2021).

The role and difficulty of measuring the specific T cell response to natural and vaccine
SARS-CoV-2 immunity and its duration has been underemphasized. We are using unique immuno informatic algorithms to define peptide pools to examine T cell responses specifically to SARS-CoV-2 for studies of duration of immunity and vaccine development.