Generating an effective vaccine against genital herpes infections has been a major research challenge for decades. Likewise, a protective microbicide has been a dream as well. Scientists at the University of Illinois at Chicago, USA, and at Kiel University, Germany, have recently developed a unique method to combine microbicide efficacy with a new vaccine platform to give rise to the "Microbivac" concept. "Using specially designed nanoparticles by the Functional Nanomaterials group at Kiel University, our study develops this exciting concept and demonstrates the proof-of-principle that the Microbivac concept actually works. This could lead the way towards developing an effective microbicide as well as an effective intravaginal vaccine to curb genital herpes, a growing health problem and a prime cofactor in the spread of HIV/AIDS", says Professor Deepak Shukla from the University of Illinois at Chicago. The co-first authors of the study, Drs. Thessicar Antoine and Satvik Hadigal (UIC), reemphasize that a non-traditional vaccine design, such as the one developed by the team, is the only solution to this growing health problem. The results of the study have been published in the Journal of Immunology.

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Both pictures show zinc oxide tetrapods; right: virus is bound to tetrapod
Image Credit: Deepak Shukla

The promising "Microbivac" concept relies on complex shaped ZnO tetrapods that have been synthesized by the novel "flame transport synthesis technology" in the laboratory in Kiel. Since this technique involves a solvent-free synthesis approach without the use of additional chemicals, the obtained structures are quite pure, which facilitates interesting biomedical applications. "These ZnO tetrapods are significantly biocompatible. At the same time, their unique nanoscale physical and chemical features are suitable for antiviral treatments and improving immunological activity. For this purpose, we artificially created further defects on the crystal surface with ultraviolet light, and thus enabled the binding of viral particles. Usually the defects play an important role as doping sites in ZnO-based electronics. It is fascinating to see that they have proved to be useful in an entirely different context by also being able to immobilize the genital herpes virus", says Professor Adelung from Kiel University.

"These ZnO tetrapods not only exhibit antiviral features, they can also improve the immunological responses of cells around lesions, encouraging faster wound recovery", explains Professor Bellur S. Prabhakar from the University of Illinois at Chicago. This means that when bound to ZnO, dendritic cells interact with the virus and thus trigger the production of antibodies, which work like the body's own vaccine. These antiviral and immune-activating properties make ZnO tetrapods a microbiocide and vaccine in one. The researchers call this combination Microbivac.

"The flame based technique offers large scale production of these tetrapods and hence this developed genital herpes treatment approach could be extended to industrial level in any desired form in the future, once it has been approved", says Dr. Yogendra Kumar Mishra from Kiel University. The production of the tetrapodal ZnO is currently upscaled as T-ZnO with a startup company from the university and intends to utilize a joint patent in future, with contributions from Kiel University and the University of Illinois at Chicago.

Following several years of a very successful animal testing phase, clinical studies on humans are planned for the next step. If these are equally successful then nothing will stand in the way of approving the ZnO vaccine as a medicine in the coming years. The scientists are positive that the further studies will be successful, because according to Adelung, zinc oxide has very few side effects and is already used today in a number of external treatments, such as zinc creams.

Article: Intravaginal Zinc Oxide Tetrapod Nanoparticles as Novel Immunoprotective Agents against Genital Herpes, Thessicar E. Antoine, Satvik Hadigal, Abraam Yakoub, Yogendra Kumar Mishra, Palash Bhattacharya, Christine Haddad, Tibor Valyi-Nagy, Rainer Adelung, Bellur S. Prabhakar, Deepak Shukla, Journal of Immunology, doi: 10.4049/jimmunol.1502373, published online 27 April 2016.