U.S. Navy Advances Dengue DNA Vaccine Using Vical's Vaxfectin® Adjuvant
SAN DIEGO, March 5, 2012 (GLOBE NEWSWIRE) -- Vical Incorporated (Nasdaq:VICL) today announced that the Naval Medical Research Center (NMRC) has initiated a Phase 1 human clinical trial of a tetravalent dengue DNA vaccine formulated with the company's Vaxfectin® adjuvant. The trial is based on exciting efficacy data from a nonhuman primate study recently published in the journal Vaccine1. Vical manufactured the vaccine and the adjuvant for both the preclinical and clinical studies, and is providing regulatory and clinical expertise to NMRC for the dengue program.
Vical completed three prior Phase 1 trials, with no safety issues and no dose-limiting toxicity, of Vaxfectin®-formulated DNA vaccines against H5N1 and H1N1 pandemic influenza.
Under a prior Collaborative Research and Development Agreement (CRADA) with Vical, NMRC developed a tetravalent DNA vaccine (TVDV) containing genes encoding the pre-membrane (prM) and envelope (E) proteins for all four serotypes of dengue virus, and formulated with Vical's Vaxfectin® adjuvant. Both Vaxfectin®-formulated and unformulated vaccines are now being evaluated in Phase 1 human testing. A total of 40 subjects will be assigned to three dose groups: a low dose TVDV without adjuvant, a low dose TVDV with Vaxfectin® adjuvant, or a high dose TVDV with Vaxfectin® adjuvant. Vaccines will be administered by intramuscular injections on days 0, 30 and 90, with follow-up through approximately one year. Key endpoints in the trial will be safety and immunogenicity.
The recently published preclinical TVDV immunogenicity and challenge data indicated that Vaxfectin® significantly improved neutralizing antibody responses and significantly enhanced protection against challenge. Nonhuman primates received the tetravalent DNA vaccine, formulated with or without the Vaxfectin® adjuvant, or a blank DNA control, on days 0, 28, and 84. All four (100%) rhesus macaques receiving the Vaxfectin®-formulated vaccine developed neutralizing antibodies to all four serotypes of dengue by one month after the second injection, compared with none of the four (0%) macaques receiving the unformulated vaccine and none of the three (0%) unvaccinated control animals. By one month after the third injection, all (100%) macaques in both vaccine groups (Vaxfectin®-formulated and unformulated) developed neutralizing antibodies to all four serotypes of dengue, compared with none (0%) of the unvaccinated control animals.
Macaques receiving the Vaxfectin®-formulated vaccine were highly protected against challenge with DEN-2, exhibiting very limited viremia (group mean 0.75 days). Macaques receiving unformulated vaccine were only partially protected against challenge (group mean 2.00 days). Unvaccinated control macaques were unprotected against challenge, exhibiting typical viremia (group mean 3.33 days).
According to the World Health Organization (WHO), up to 2.5 billion people across the world are at risk for dengue infections. Dengue virus infects up to 100 million and results in over 500,000 hospitalizations and 12,500 deaths each year. Its impact is magnified by the lack of effective antiviral drugs and vaccines.
Dengue fever can be caused by any one of four serotypes of dengue virus: DEN-1, DEN-2, DEN-3 and DEN-4. These viruses are part of the Flavivirus family, which includes West Nile virus and yellow fever virus. Dengue virus is spread by mosquitoes, and is most common during the rainy seasons throughout the world's tropical and subtropical regions. Dengue does not spread directly from person to person. An individual infected by one serotype of dengue virus develops lifelong immunity against that serotype, but not against other serotypes.
Symptoms of classic dengue fever include high fever, severe headache and/or pain behind the eyes, severe joint and muscle pain, nausea and vomiting. A few days after fever onset, a rash often develops over most of the body and lasts for one to two days. The rash can reappear several days later. These symptoms typically begin within a week after infection, and usually resolve without treatment.
Dengue hemorrhagic fever is a more serious form of disease which can include all of the symptoms of classic dengue fever plus leakage of blood plasma into tissues caused by noticeable damage to blood vessels and lymph vessels, bleeding from the nose and gums, and conspicuous bruising under the skin. Dengue hemorrhagic fever can lead to death. The most severe form of dengue disease is dengue shock syndrome, which includes all of the symptoms of classic dengue and dengue hemorrhagic fever, plus massive leaking of blood plasma outside of blood vessels, extensive bleeding, and shock caused by extremely low blood pressure. Dengue shock syndrome most often occurs in children infected for a second time (with a different serotype of dengue), and can be fatal.
Dengue disease, including classic dengue, dengue hemorrhagic fever and dengue shock syndrome, is increasing in both incidence and severity throughout many tropical regions of the world, especially in Southeast Asia, the Indian subcontinent, Central and South America, and Africa.
Vical researches and develops biopharmaceutical products based on its patented DNA delivery technologies for the prevention and treatment of serious or life-threatening diseases. Potential applications of the company's DNA delivery technology include DNA vaccines for infectious diseases or cancer, in which the expressed protein is an immunogen; cancer immunotherapeutics, in which the expressed protein is an immune system stimulant; and cardiovascular therapies, in which the expressed protein is an angiogenic growth factor. The company is developing certain infectious disease vaccines and cancer therapeutics internally. In addition, the company collaborates with major pharmaceutical companies and biotechnology companies that give it access to complementary technologies or greater resources. These strategic partnerships provide the company with mutually beneficial opportunities to expand its product pipeline and address significant unmet medical needs. Additional information on Vical is available at www.vical.com.
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This press release contains forward-looking statements subject to risks and uncertainties that could cause actual results to differ materially from those projected. Forward-looking statements include statements about the continued development of a tetravalent, Vaxfectin®-formulated DNA vaccine for dengue, and the potential effect of the company's Vaxfectin® adjuvant on vaccine performance. Risks and uncertainties include the completion of Phase 1 testing and whether any further development of the dengue vaccine will continue; whether dengue vaccine or other results in animal studies can be duplicated in human clinical trials; whether the dengue vaccine will be effective in protecting humans against dengue infection or disease; whether the dengue vaccine will achieve the safety and immunogenicity endpoints in the Phase 1 trial; whether Vical or its collaborative partners will seek or gain approval to market any product candidates; whether Vical or its collaborative partners will succeed in marketing any product candidates; and additional risks set forth in the company's filings with the Securities and Exchange Commission. These forward-looking statements represent the company's judgment as of the date of this release. The company disclaims, however, any intent or obligation to update these forward-looking statements.
1Porter, KR, et al. Immunogenicity and protective efficacy of a Vaxfectin-adjuvanted tetravalent dengue DNA vaccine. Vaccine 30 (2012) 336-341; doi:10.1016/j.vaccine.2011.10.085 .
CONTACT: Alan R. Engbring