The trial will evaluate the safety, tolerability and immunogenicity of the prophylactic mRNA candidate in preventing genital lesions caused by the viruses.
Herpes Simplex Virus-1 (HSV-1) and Herpes Simplex Virus-2 (HSV-2) cause two highly prevalent viral infections globally. Up to 95% of the global population are estimated to be infected by herpes with most of the infections remaining asymptomatic, but symptoms of herpes include painful blisters or ulcers that can recur over time.
HSV-2 is a sexually transmitted disease that causes genital herpes. Furthermore, HSV-2 infection increases the risk of acquiring HIV infections by approximately three-fold, and co-infections with both HIV and HSV-2 increase the likelihood of transmitting HIV to others, according to the WHO.
HSV-1 is mainly transmitted by oral contact and causes lesions around the mouth but in some cases can also lead to genital infections and respective lesions.
As neurotropic and neuroinvasive viruses, HSV-1 and -2 persist in the body by hiding from the immune system in the cell bodies of neurons where they reside lifelong, and thus cannot be eradicated with current treatments (Currently available HSV therapies only reduce the severity and frequency of symptoms.)
No vaccine has been approved for prevention of genital lesions caused by HSV to date.
The vaccine
The mRNA vaccine candidate encodes three HSV-2 glycoproteins with the aim of helping to prevent HSV cellular entry and spread, as well as counteract the immunosuppressive properties of HSVs.
It has been developed via a research collaboration and license agreement between BioNTech and The University of Pennsylvania as part of a 2018 agreement to develop novel mRNA vaccine candidates for infectious diseases. (Under the terms of the agreement, BioNTech can obtain an exclusive worldwide license to further develop and commercialize product candidates arising from the research collaboration.) After completion of all IND-enabling studies, BNT163 is the first candidate from this collaboration to enter the clinic.
A placebo-controlled, observer blinded, dose-escalation Phase 1 trial is expected to enroll around 100 healthy volunteers aged 18 to 55 years without current or history of symptomatic genital herpes infections in the US. The study consists of a first dose escalation part that will focus on safety evaluations and assess the optimal dose-response in various dose levels.
The second part of the trial is designed to expand the safety characterization for the selected dosing of BNT163 for a more comprehensive assessment of the impact of pre-existing immunity to HSV-1 and -2 on the safety and BNT163-induced immune responses.
“This program is part of our strategy to help address diseases with a high unmet medical need and of global health relevance by combining our new technologies such as mRNA and our expertise in immune engineering,” said Prof. Özlem Türeci, M.D., Chief Medical Officer and Co-Founder of BioNTech. “BNT163 is based on three non-infectious mRNA-encoded HSV-2 glycoproteins. We aim to induce a broad immune response which is directed against multiple antigens of the virus and mobilizes various immune effectors to support virus neutralization and clearance.”