Skip to main content
Breadcrumb

Development of a vaccine against herpes simplex virus 2 infection

Research project
Active research
Project owner
Institute of Biomedicine

Short description

Herpes simplex virus 2 (HSV-2) causes genital herpes and infects the genital mucosa followed by a lifelong infection of the nervous system. Globally, about 500 million people are infected. After primary infection, HSV-2 reactivates and sometimes produces painful genital blisters and ulcers, but most often the virus is excreted without symptoms. We develop a vaccine against HSV-2 infection based on the HSV-2 type-specific protein gG. We are now in the final phase of preclinical development and are now planning a phase I clinical trial.

Herpes simplex virus 2 (HSV-2) is the most prevalent sexually transmitted infection causing painful and recurrent genital blisters, sometimes with meningitis. HSV-2 can also cause life-threatening encephalitis in newborns and immunocompromised patients. Finally, HSV-2 infected patients suffer a three-fold increased risk of HIV acquisition. We conclude that there is a great need for both a therapeutic and a prophylactic vaccine.

We use a novel strategy to develop a vaccine against HSV-2 infection. Based on the observations that cross- reactive immune responses from a prior HSV-1 infection do not provide protection against subsequent HSV-2 infection, and that several human vaccine trials using cross-reactive antigens have failed, we suggest that a vaccine should be based on a component type-specific for HSV-2. This protein is glycoprotein G-2 (gG-2).

The proof of concept is:

  • Identification of a lead vaccine candidate of 25 gG-2 molecules analyzed
  • The vaccine is based on a truncated variant of gG-2
  • The protein is highly immunogenic together with adjuvant (CpG+alum) and induces 90% protection in a mouse vaccination model
  • Definition of production by recombinant technique in CHO cells and a purification process
  • The modified gG-2 has a great potential to be the lead diagnostic antigen for detection of HSV- 2 specific antibodies

The concept to use a type-specific recombinant protein as a vaccine for herpes virus infections has recently been supported by the registration of the very effective vaccine (GSK) against herpes zoster based on the type-specific protein (gE). Interestingly, the gE-vaccine induced higher and more prolonged Th1 responses as compared with live attenuated zoster virus.

We have collaborated with NIH and evaluated the vaccine in a guinea pig vaccination model and showed that high antibody anti-gG-2 IgG levels were detected after vaccination.

To further develop the vaccine with the goal to evaluate the vaccine in clinical trials, the next challenges are i) optimize production of the gG-2 antigen by recombinant technique in CHO cells to increase the yield, and ii) production of antigen for toxicity and safety program as well as for clinical studies, iii) commercial production of the antigen, and iv) to get financial support for further development.

Group leader

Jan-Åke Liljeqvist

jan-ake.liljeqvist@gu.se

 

List of Publication

Group member

Tomas Bergström

Staffan Görander