Hexon hypervariable region-modified adenovirus type 5 (Ad5) vectors display reduced hepatotoxicity but induce T lymphocyte phenotypes similar to Ad5 vectors

Jeffrey E. Teigler, Pablo Penaloza-MacMaster, Rebecca Obeng, Nicholas M. Provine, Rafael A. Larocca, Erica N. Borducchi, Dan H. Barouch*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Hexon modification of adenovirus type 5 (Ad5) vectors with the hypervariable regions (HVRs) of Ad48 has been shown to allow Ad5HVR48 vectors to circumvent the majority of the preexisting Ad5-neutralizing antibodies. However, it remains unclear whether modifying hexon HVRs impacts innate or adaptive immune responses elicited by this vector. In this study, we investigated the influence of the HVR substitution of Ad5 on innate and adaptive immune responses following vaccination. Ad5HVR48 displayed an intermediate level of innate immune cytokines and chemokines relative to those of Ad5 and Ad48, consistent with its chimeric nature. Hepatotoxicity was observed after Ad5 immunization but not after Ad5HVR48 or Ad48 immunization. However, the CD8 + T-cell responses elicited by Ad5HVR48 vectors displayed a partially exhausted phenotype, as evidenced by the sustained expression of programmed death 1 (PD-1), decreased effector-to-central memory conversion, and reduced memory recall responses, similar to those elicited by Ad5 vectors and in contrast to those induced by Ad48 vectors. Taken together, these results indicate that although Ad5HVR48 largely bypasses preexisting Ad5 neutralizing antibodies and shows reduced hepatotoxicity compared to that of Ad5, it induces adaptive immune phenotypes that are functionally exhausted similar to those elicited by Ad5.

Original languageEnglish (US)
Pages (from-to)1137-1144
Number of pages8
JournalClinical and Vaccine Immunology
Volume21
Issue number8
DOIs
StatePublished - Aug 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

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