Researchers offer new insights into how herpes simplex virus antibodies work

Results of a new study led by a team of researchers from the Geisel School of Medicine and the Thayer School of Engineering at Dartmouth and published in Cell Reports Medicine provide new insights into how antibodies work in fighting herpes simplex virus (HSV) infections. The research could lead to possible new treatments for neonatal herpes.

Herpes simplex virus infections are common and usually affect the skin and nervous system. They are caused by two related but distinct viruses: type 1 (HSV-1), which more commonly causes infections around the mouth and occurs in up to 80 to 90% of older people, and type 2 (HSV- 2), which more frequently causes infections around the mouth. genital infections and can be found in 20-30% of adults.

Although these viruses often remain latent in the body and generally do not pose serious health risks, HSV can be more dangerous for people with weakened immune systems. In some cases, HSV can cause corneal blindness and brain infections, and may also be associated with neurodegeneration and Alzheimer’s disease. Neonatal herpes simplex virus infections are particularly devastating – serious infections can spread to internal organs and the brain – and are one of the deadliest neonatal infections.

“Despite three decades of effort, the scientific community has been unable to develop an effective herpes vaccine, and I think the main problem is that we haven’t fully understood what we need, in terms of antibodies and their specific functions, to fight against herpes. protect against this disease,” says David Leib, Ph.D., chair and professor of microbiology and immunology at Geisel, who served as corresponding author of the study with Margaret Ackerman, Ph.D., professor of engineering at Thayer.

As they have often done in the past, Leib and Ackerman partnered on the project, combining the expertise and resources of their laboratories while co-supervising the work of Matthew Slein, a Ph.D. candidate in the Leib and Ackerman laboratories, and Iara Backes, MD-Ph.D. student at Geisel, who served as co-first author of the study.

In their experiments, the research team used a neonatal mouse model to mimic human neonatal infections, creating antibodies with different properties to explore how they provide protection.

“What Matt and Iara discovered was something unexpected,” says Leib. “It is not only the neutralizing capacity of antibodies, that is to say their ability to bind directly to the virus and prevent it from entering the cell, that is important. The effector functions, which allow antibodies to interact with other parts of the immune system, also play a crucial role, a role that has been largely overlooked in the past.”

Slein and Backes also discovered key differences between HSV-1 and HSV-2 infections and that each requires different antibody properties for optimal protection. Importantly, their results suggest a better way to design vaccines and could help explain why many vaccine candidates have failed to provide protection in clinical trials in the past.

“Another important aspect of the work that Matt and Iara are doing is that we now have very good monoclonal antibodies that we have made in the laboratory that could potentially be used directly as a drug to treat acute neonatal herpes infections, which are “life-threatening diseases for newborns,” says Leib.

“Monoclonal antibodies have been used to treat cancer and other diseases and show promise as a therapy for infectious diseases,” he says. “This would be a tremendous breakthrough, because antiviral drugs like acyclovir have only been shown to be partially effective in treating these very sick children.”