Human immunodeficiency virus (HIV) infections continues to be a major public health problem worldwide. Though the initial work towards HIV-1 vaccine development began over a decade ago, an efficacious prophylactic HIV vaccine does not exist, and only a few candidate vaccines have reached Phase I and II clinical trials. Two major obstacles have significantly hampered these efforts: a) limitations on the current vectors being employed for delivery of HIV immunogens and b) lack of appropriate envelope neutralizing antibody response against primary isolates. The purpose of this proposal is twofold: 1) to evaluate the immunogenicity of an HIV envelop glycoprotein from a primary isolate, which will be incorporated into HIS or HIV psuedovirions to preserve its native structure and 2) top develop genetically engineered herpes simplex viruses (HSV) as a vehicle for delivery of these pseudovirions. For these studies, the investigations will adapt a prototype HSV vaccine vector previously tested in humans to serve as the backbone for this HIV vaccine.
The specific aims of this proposal are: 1. Develop genetically engineered HSV which express HIV or SIV gag genes and HIV env genes as candidate vaccines against HIV infection. 2. Evaluate the recombinant HSV in vitro for (a) replicative competence, (b) continued sensitivity to common antiviral drugs (c) expression of HIV/SIV Gag and HIV Env proteins, and (c) assembly and release of HIV or SIV pseudovirions containing HIV envelope glycoproteins. 3. Assess the humoral immune responses elicited by these viruses in a murine model for specificity and neutralization activity.
| Parker, Scott D; Rottinghaus, Scott T; Zajac, Allan J et al. (2007) HIV-1(89.6) Gag expressed from a replication competent HSV-1 vector elicits persistent cellular immune responses in mice. Vaccine 25:6764-73 |
| Parker, Jacqueline N; Pfister, Luz-Andrea; Quenelle, Debra et al. (2006) Genetically engineered herpes simplex viruses that express IL-12 or GM-CSF as vaccine candidates. Vaccine 24:1644-52 |
