Comparison of replication-competent, first generation, and helper-dependent adenoviral vaccines

Eric A Weaver, Pramod N. Nehete, Stephanie S. Buchl, Julien S. Senac, Donna Palmer, Philip Ng, K. Jagannadha Sastry, Michael A. Barry

Research output: Contribution to journalArticle

52 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere5059
JournalPloS one
Volume4
Issue number3
DOIs
StatePublished - Mar 31 2009

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Adenoviridae
serotypes
Vaccines
vaccines
immune response
Helper Viruses
HIV
Safety
Adenovirus Vaccines
viruses
gene therapy
mice
vaccine development
Macaca
Neutralizing Antibodies
Viruses
neutralizing antibodies
Genetic Therapy
Genes
genes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Weaver, E. A., Nehete, P. N., Buchl, S. S., Senac, J. S., Palmer, D., Ng, P., ... Barry, M. A. (2009). Comparison of replication-competent, first generation, and helper-dependent adenoviral vaccines. PloS one, 4(3), [e5059]. https://doi.org/10.1371/journal.pone.0005059

Comparison of replication-competent, first generation, and helper-dependent adenoviral vaccines. / Weaver, Eric A; Nehete, Pramod N.; Buchl, Stephanie S.; Senac, Julien S.; Palmer, Donna; Ng, Philip; Sastry, K. Jagannadha; Barry, Michael A.

In: PloS one, Vol. 4, No. 3, e5059, 31.03.2009.

Research output: Contribution to journalArticle

Weaver, EA, Nehete, PN, Buchl, SS, Senac, JS, Palmer, D, Ng, P, Sastry, KJ & Barry, MA 2009, 'Comparison of replication-competent, first generation, and helper-dependent adenoviral vaccines', PloS one, vol. 4, no. 3, e5059. https://doi.org/10.1371/journal.pone.0005059
Weaver, Eric A ; Nehete, Pramod N. ; Buchl, Stephanie S. ; Senac, Julien S. ; Palmer, Donna ; Ng, Philip ; Sastry, K. Jagannadha ; Barry, Michael A. / Comparison of replication-competent, first generation, and helper-dependent adenoviral vaccines. In: PloS one. 2009 ; Vol. 4, No. 3.
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