Creating Live Attenuated HSV-2 Vaccine Candidate Strains Through Codon Pair Bias Deoptimization

Abstract

Herpes simplex virus 2 (HSV-2) is the primary causative agent of genital herpes, a disease characterized by painful recurrent anogenital lesions, higher risks for HIV and other STD transmissions, and potential childbirth complications. Despite the large medical burden of HSV-2, no vaccines are currently available. Most HSV-2 vaccine candidates have been subunit vaccines due to safety concerns, but live attenuated vaccines (LAVs) should be considered. Codon pair bias (CPB) is the phenomenon that specific codons pairs appear more frequently than expected. CPB deoptimization (CPBD) has been shown to significantly attenuate polio, influenza, and Streptococcus pneumoniae, indicating that CPBD is a viable attenuation method and LAV strategy. However, CPBD has never been used to attenuate DNA viruses, so its ability to attenuate these viruses remains unknown. This thesis describes the usage of CPBD to deoptimize specific HSV-2 genes to create potential HSV-2 LAV candidates.