Novel Mucosal Adjuvant for an HIV DNA Vaccine

DESCRIPTION provided by applicant Our primary approach to develop an effective prophylactic vaccine against HIV utilizes a novel immunogen called the Full Length Single Chain FLSC that consists of gp derived from HIV genetically linked via a amino acid linker to the D D domains of human CD When rhesus macaques were inoculated with versions of FLSC that contain CD derived from rhesus macaques and either HIV gp or SIV gp significant protection against rectal challenge with multiple low doses of either an R tropic heterologous SHIV P or heterologous SIVmac was observed These observations propelled FLSC into preclinical development and evaluation in a phase clinical trial supported by BMGF MHRP NIAID Further vaccination with DNA expressing FLSC and IL administered by electroporation in macaques induces multifunctional T cells that are known to correlate with protection and improved efficacy In our most recent macaque study a FLSC DNA prime protein boost regimen yielded efficacy against a cross clade challenge In collaboration with others we have also developed a DNA protein co delivery regimen that evokes higher titered longer lived anti FLSC responses However we believe that our approach can be dramatically improved by targeting these anti FLSC responses to mucosal sites where HIV enters the host and establishes infections To improve mucosal immune responses we sought to develop a mucosal homing DNA adjuvant that targets lymphocytes to mucosal immune effector sites after systemic vaccination In preliminary studies we identified two putative mucosal homing DNA adjuvants Under phase I we demonstrated that one of these putative adjuvants does indeed induce the homing of lymphocytes to mucosal immune effector sites after systemic i m immunization Under phase II we intend to expand upon these observations and demonstrate that this adjuvant targets vaccine specific immune responses to mucosal sites in primates PUBLIC HEALTH RELEVANCE The objective of this project is to determine if a mucosal homing DNA adjuvant will improve the immune responses generated by our HIV SIV vaccine regimen