In February 2024 a team from Dartmouth’s Geisel School of Medicine and Thayer School of Engineering announced that their research in Cell Reports offers “new insights” into how antibodies function in “combating” herpes simplex virus (HSV) infections. The study outlines how effector functions are “crucial” for protection by glycoprotein D (gD)-specific mAbs. It is hoped that this progress could facilitate treatments for neonatal herpes.
HSV
Herpes simplex virus infections are “common” and “typically” affect the skin and nervous system. They often lie dormant in the body without posing a serious health risk but can be “more dangerous for those with weak immune systems”. Neonatal herpes simplex virus infections are “particularly devastating”, with the potential for infections to spread to internal organs and the brain, causing “loss of life or long-term neurological disability”.
Although new treatment regimens have “improved outcomes”, the authors describe neonatal mortality following disseminated disease “unacceptably high”. Therefore, they identify a need for insights into “how Abs exert direct and indirect antiviral activities to protect against infection could aid in the design of both passive and active immunisation strategies”.
“Like other consequential early-life pathogens, most studies of HSV have focused on adult animal models. There is therefore a dearth of information on how Abs protect in the neonatal period.”
The team set out to investigate the mechanism(s) by which Abs that target gD mediate protection against nHSV-1 and nHSV-2 infections. Through a mouse model of nHSV infection they were able to demonstrate “distinct mechanisms” of Ab-mediated protection that differ between viral types.
Understanding the need
Dr David Leib, chair and professor of microbiology and immunology, commented that “despite three decades of trying, the scientific community has been unable to develop an effective vaccine against herpes”.
“I think the main issue has been that we haven’t fully understood what we need, in terms of antibodies and their specific functions, to protect against this disease.”
Dr Leib was surprised by the results, suggesting that the team discovered “something unexpected”.
“It’s not just the neutralising capability of antibodies, that is, their ability to bind directly to the virus and prevent it from entering the cell, that is important. Effector functions, which allow the antibodies to interface with other parts of the immune system, also play a critical role – one that has been largely overlooked in the past.”
The paper states that this research could contribute to mAb-based prevention and therapy as well as vaccine design. The authors emphasise the conclusion that “polyfunctional mAbs able to mediate both neutralisation and effector functions” will be the “best candidates” for therapeutic and prophylactic translation.
“Expanding the focus of vaccine research and development to include activities beyond viral neutralisation has the potential to accelerate the quest for interventions to reduce the global burden of HSV infection.”
How can we accelerate research and innovation to improve vaccine outcomes for neonates and older populations? To join the discussion at the Congress in Washington this April get your tickets here and don’t forget to subscribe!
