Study Sheds Light on Antibody Functions in Herpes Simplex Virus Defense

The results of a recent study led by the Geisel School of Medicine and Thayer School of Engineering at Dartmouth, and published in Cell Reports Medicine, provide new information about the role that antibodies play in preventing herpes simplex virus (HSV) infections. The study could result in novel therapies for newborn herpes. 
Infections with the Herpes simplex virus are frequent and usually affect the skin and nervous system.

These are brought on by two closely related but different viruses: type 1 (HSV-1), which affects 80–90% of older individuals and is more common to cause oral infections, and type 2 (HSV-2), which affects 20–30% of adults and is more common to cause genital infections.  

Although HSV can be more harmful to those with weakened immune systems, these viruses often don’t pose a major risk to health because they often remain latent in the body. HSV may occasionally result in brain infections and corneal blindness. It may also be linked to neurodegeneration and Alzheimer’s disease. One of the deadliest infections in babies is the herpes simplex virus, which can spread to the brain and other organs. Severe infections can be extremely damaging.  

“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,” says David Leib, Ph.D., chair and professor of microbiology and immunology at Geisel, who served as a corresponding author on the study with Margaret Ackerman, Ph.D., professor of engineering at Thayer. “Despite three decades of trying, the scientific community has not been able to develop an effective vaccine against herpes,” he says.  
Leib and Ackerman collaborated on the project, as they frequently have, pooling their labs’ resources and experience to co-supervise the work of Matthew Slein, a Ph.D. candidate in their labs, and Iara Backes, an MD-Ph.D. candidate at Geisel, who were co-first authors on the study.  

The research team engineered antibodies with diverse properties to investigate how they mediate protection, and they utilized a newborn mouse model to imitate human neonatal illnesses.  
“What Matt and Iara have discovered is something unexpected,” Leib explains. “What matters is not merely an antibody’s neutralizing potential, or its capacity to attach itself to the virus and stop it from infecting a cell. A crucial role that has previously been mostly disregarded is played by effector functions, which enable the antibodies to interact with other immune system components.”  

Additionally, Slein and Backes discovered that HSV-1 and HSV-2 infections differ significantly from one another and that distinct antibody characteristics are needed for the best defense. Notably, their findings suggest a more effective approach to vaccine development and could assist to clarify the reasons behind the numerous vaccine candidates that have not proven to be protective in previous clinical trials.  
“Another important aspect of the work that Matt and Iara have done is that we now have some really good monoclonal antibodies that we’ve made in the lab that could potentially be used directly as a medication to treat acute neonatal herpes infections, which are life-threatening to newborns,” Leib adds.  
 
“Monoclonal antibodies have been used to treat cancer and other diseases and show promise as a therapy for infectious disease,” according to him. This would be a wonderful development, as antiviral drugs like acyclovir have only proven to be partially effective in treating these very sick kids. 

Journal Reference  

Matthew D. Slein et al, Effector functions are required for broad and potent protection of neonatal mice with antibodies targeting HSV glycoprotein D, Cell Reports Medicine (2024). DOI: 10.1016/j.xcrm.2024.101417