Christy K. Jurgens

Viral vector delivery of Env trimer immunogens

Methods We are using vesicular stomatitis virus (VSV) as a vector platform for delivery of Env immunogens as transmembrane glycoproteins. We have investigated a variety of vector designs and Env modifications to identify combinations that balance the practical requirement for vector genetic stability with factors influencing antibody responses including immunogen abundance, efficient post-translational processing, and presentation of antigenic determinants representative of a functional trimeric spike.

Optimizing expression of functional HIV envelopes in rVSV-ΔG vaccine vectors.

Methods Using a combination of nucleotide sequence optimization and protein domain swapping, we have generated a panel of novel gene inserts for VSV vectors that encode chimeric HIV-1 and VSV glycoprotein immunogens (EnvG). A stable VERO cell line engineered to express human CD4 and CCR5 was used to rescue rVSV vectors in which the G gene was replaced with coding sequence for several different EnvG proteins.

Development of candidate HIV vaccines using VSV vectors to express membrane-anchored MPER immunogen

Background The HIV-neutralizing activity of monoclonal antibodies 2F5, 4E10, and Z13 have shown that the membrane-proximal external region (MPER) of HIV Env is an important vaccine target, but development of an immunogen that elicits similar virus-neutralizing antibody responses against the MPER from a wide range of subtypes has been difficult to achieve. It has been proposed that a MPER immunogen must be membrane-associated to adopt the conformation needed to elicit broadly neutralizing antibodies, and accordingly, we have developed Vesicular Stomatitis Virus (VSV) Vectors that express membrane-anchored MPER epitopes.