Comparison of Replication-Competent, First Generation, and Helper-Dependent Adenoviral Vaccines

Authors

Eric A. Weaver, University of Nebraska-Lincoln & Mayo Clinic, RochesterFollow
Pramod N. Nehete, The University of Texas M.D. Anderson Cancer Center, Houston
Stephanie S. Buchl, The University of Texas M.D. Anderson Cancer Center, Houston
Julien S. Senac, Baylor College of Medicine, Houston
Donna Palmer, Baylor College of Medicine, Houston
Philip Ng, Baylor College of Medicine, HoustonFollow
K. Jagannadha Sastry, The University of Texas M.D. Anderson Cancer Center, Houston & he University of Texas M.D. Anderson Cancer Center, Houston
Michael A. Barry, Mayo Clinic, RochesterFollow

Document Type

Article

Date of this Version

2009

Citation

Weaver EA, Nehete PN, Buchl SS, Senac JS, Palmer D, et al. (2009) Comparison of Replication-Competent, First Generation, and Helper-Dependent Adenoviral Vaccines. PLoS ONE 4(3): e5059. doi:10.1371/journal.pone.0005059

Comments

2009 Weaver et al

Abstract

All studies using human serotype 5 Adenovirus (Ad) vectors must address two major obstacles: safety and the presence of pre-existing neutralizing antibodies. Helper-Dependent (HD) Ads have been proposed as alternative vectors for gene therapy and vaccine development because they have an improved safety profile. To evaluate the potential of HD-Ad vaccines, we compared replication-competent (RC), first-generation (FG) and HD vectors for their ability to induce immune responses in mice. We show that RC-Ad5 and HD-Ad5 vectors generate stronger immune responses than FG-Ad5 vectors. HD-Ad5 vectors gave lower side effects than RC or FG-Ad, producing lower levels of tissue damage and anti-Ad T cell responses. Also, HD vectors have the benefit of being packaged by all subgroup C serotype helper viruses. We found that HD serotypes 1, 2, 5, and 6 induce anti-HIV responses equivalently. By using these HD serotypes in heterologous succession we showed that HD vectors can be used to significantly boost anti-HIV immune responses in mice and in FG-Ad5-immune macaques. Since HD vectors have been show to have an increased safety profile, do not possess any Ad genes, can be packaged by multiple serotype helper viruses, and elicit strong anti-HIV immune responses, they warrant further investigation as alternatives to FG vectors as gene-based vaccines.