About Zika Virus. Zika disease is a rapidly spreading emerging infection caused by the Zika virus (ZIKV) and is linked to microcephaly in infants and Guillain-Barre syndrome (a neurodegenerative disease) in adults. ZIKV is a member of the Flaviviridae family, which includes medically important pathogens such as dengue fever, yellow fever, Japanese encephalitis, tick-borne encephalitis, and West Nile viruses. ZIKV, which was first discovered in 1947 in the Zika forest of Uganda, was considered only a minor public health concern for 60 years. Recently, with its appearance and rapid spread in the Americas, it has emerged as a serious threat with pandemic potential. Symptoms of Zika infection have historically been mild. In the recent epidemic, however, an alarming association between ZIKV infection and fetal brain abnormalities including microcephaly were suspected and later confirmed by strong scientific evidence. No approved preventive or therapeutic products are currently available to fight the Zika epidemic. Public health officials recommend avoiding exposure to ZIKV, delaying pregnancy, and following basic supportive care (fluids, rest, and acetaminophen) after infection. A vaccine is urgently needed to prevent a Zika pandemic.
Our Vaccine. To address the unmet need for a ZIKV vaccine, we are developing a novel vaccine candidate by expressing the ZIKV NS1 protein (designated GEO-ZM02) in our MVA-vector platform, which has already shown great promise in our HIV and Ebola vaccines. We have received a Small Business Innovative Research (SBIR) grant of $600,000 from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), in support of advanced preclinical development of this novel Zika vaccine candidate. The grant, entitled "Advanced Preclinical Testing of a Novel Recombinant Vaccine Against Zika Virus", will support preclinical testing of GeoVax's vaccine candidates in non-human primates in preparation for the initiation of a Phase 1 human clinical study. The studies funded by this grant will build upon previous work demonstrating the protective efficacy of recombinant vaccines using GeoVax's MVA live viral vector. We are particularly excited about GEO-ZM02, which recently demonstrated 100% single-dose protection in normal mice against a lethal dose of ZIKV delivered by intracerebral inoculation. GEO-ZM02 not only has the potential of a single-dose vaccine, which is practical to combat epidemics in resource-strained countries, but also does not bear the risk of enhancing other flavivirus infections, such as Dengue and West Nile viruses, in vaccinated subjects. This phenomenon, called Antibody Dependent Enhancement (ADE) of infection, has been shown to increase severity of DENV infection in vivo, and is a safety concern for other Zika vaccines under development that utilize the structural Envelope (E) protein of ZIKV for their vaccine construct. GEO-ZM02 is based on the non-structural-1 (NS1) protein of ZIKV, which is not packaged into the virions and is not involved in ADE. Moreover, the NS1 protein is abundantly secreted into the blood of a ZIKV-infected individual and plays a critical role in flavivirus acquisition by mosquitoes by overcoming the immune barrier of the mosquito midgut. Therefore, GEO-ZM02 has the potential to protect both humans and mosquitoes from ZIKV infection; a novel vaccination strategy that could stem epidemics at a low vaccine coverage. Our primary collaboration on the development of a ZIKV vaccine is with the US Centers for Disease Control (CDC) who performed all preclinical immunogenicity and efficacy studies. ZIKV and reagents will be supplied by the University of Texas Medical Branch (UTMB). Working with multiple collaborators and multiple candidate vaccines, we will manage risk by providing multiple paths toward the selection of the best vaccine candidate. The results of our preclinical immunogenicity and efficacy studies are published in Nature's Scientific Reports at: Scientific Reports 7, Article number: 14769(2017)doi:10.1038/s41598-017-15039-8.