A Protective Tetravalent Vaccine Candidate for Dengue Fever Virus

DESCRIPTION provided by applicant There are approximately million cases of dengue fever each year with billion people at risk mostly in low income countries There are four serotypes of dengue fever virus DENV and in its uncomplicated form the disease is worthy of its indigenous name andquot break bone feverandquot An individual may suffer sequential infections with multiple DENV serotypes and a second infection is associated with increased risk of dengue hemorrhagic fever dengue shock syndrome DHF DSS a much more serious and potentially fatal disease Altravax Inc AVI has developed a particulate single molecule tetravalent immunogen capable of inducing neutralizing antibodies directed against all four serotypes of DENV Global Vaccines Inc GVI a not for profit vaccine company has developed a novel adjuvant which is not only capable of promoting neutralizing antibody responses induced by other DENV immunogens but also catalyzing the induction of cell mediated immunity As recent evidence suggests that both arms of the immune response contribute to protection against DENV these two companies will collaborate to determine the effect of combining their respective technologies in an improved DENV vaccine The AVI immunogen will be tested in two forms First the protein immunogen will be produced in F cells and purified It then will be administered to Sv mice either alone with the GVI adjuvant or with alum as a positive adjuvant control In a second approach the gene for the AVI immunogen will be cloned into a Venezuelan equine encephalitis virus replicon particle VRP and the VRP will be administered to Sv mice for in vivo expression of the immunogen These formulations will be evaluated for induction of neutralizing antibodies and T cells to each of the four DENV serotypes The polyclonal sera also will be evaluated to determine whether the antibodies induced by the AVI tetravalent immunogen are directed to serotype specific neutralizing epitopes or to a neutralizing epitope s that is are conserved in each of the four serotypes The best of the formulations will be used to immunize Sv mice Serum T cells or a mixture of the two from the fully immunocompetent Sv mice will be transferred to na ve AG mice a congenic DENV sensitive mouse model to assess the ability of the induced immune responses to protect against challenge with each of the four DENV serotypes These experiments are the first to combine these two promising vaccine technologies and represent an important step in the preclinical development of a safe DENV vaccine candidate which induces both protective humoral and cellular responses and is appropriately inexpensive for the majority of persons at risk PUBLIC HEALTH RELEVANCE One third of the worldandapos s population is at risk for dengue fever virus infection Altravax Inc and Global Vaccines Inc a not for profit company will merge ther respective technologies in a new dengue vaccine candidate utilizing a single immunogen and a novel adjuvant to induce protective humoral and cellular immunity to all four dengue virus serotypes The overall goal is to advance this safe effective and inexpensive dengue vaccine approach through pre clinical studies and ultimately to clinical trials