Immunologic Dose-Response to Adenovirus-Vectored Vaccines in Animals and Humans: A Systematic Review of Dose-Response Studies of Replication Incompetent Adenoviral Vaccine Vectors when Given via an Intramuscular or Subcutaneous Route

Afrough, S. and Rhodes, S. and Evans, T. and White, R. and Benest, J.

Vaccines (Basel) (2020) 8:

DOI: 10.3390/vaccines8010131

Abstract

Optimal vaccine dosing is important to ensure the greatest protection and safety. Analysis of dose-response data, from previous studies, may inform future studies to determine the optimal dose. Implementing more quantitative modelling approaches in vaccine dose finding have been recently suggested to accelerate vaccine development. Adenoviral vectored vaccines are in advanced stage of development for a variety of prophylactic and therapeutic indications, however dose-response has not yet been systematically determined. To further inform adenoviral vectored vaccines dose identification, historical dose-response data should be systematically reviewed. A systematic literature review was conducted to collate and describe the available dose-response studies for adenovirus vectored vaccines. Of 2787 papers identified by Medline search strategy, 35 were found to conform to pre-defined criteria. The majority of studies were in mice or humans and studied adenovirus serotype 5. Dose-response data were available for 12 different immunological responses. The majority of papers evaluated three dose levels, only two evaluated more than five dose levels. The most common dosing range was 10(7)-10(10) viral particles in mouse studies and 10(8)-10(11) viral particles in human studies. Data were available on adenovirus vaccine dose-response, primarily on adenovirus serotype 5 backbones and in mice and humans. These data could be used for quantitative adenoviral vectored vaccine dose optimisation analysis.

Citation

Afrough, S., Rhodes, S., Evans, T., White, R., & Benest, J. (2020). Immunologic Dose-Response to Adenovirus-Vectored Vaccines in Animals and Humans: A Systematic Review of Dose-Response Studies of Replication Incompetent Adenoviral Vaccine Vectors when Given via an Intramuscular or Subcutaneous Route. Vaccines (Basel), 8(1). https://doi.org/10.3390/vaccines8010131 adenoviral vector vaccines using the vectors ChAdOx1 and ChAdOx2., adenovirus-vectored vaccines, clinical, dose-response, dosing, immunogenicity, pre-clinical

Keywords

• adenoviral vector vaccines using the vectors ChAdOx1 and ChAdOx2.
• adenovirus-vectored vaccines
• clinical
• dose-response
• dosing
• immunogenicity
• pre-clinical