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

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 107–1010 viral particles in mouse studies and 108–1011 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.

Heterologous Combination of ChAdOx1 and MVA Vectors Expressing Protein NS1 as Vaccination Strategy to Induce Durable and Cross-Protective CD8+ T Cell Immunity to Bluetongue Virus

“…The dose of the viral vectors ChAdOx1 (10 9 UI/sheep) and MVA (10 8 PFU/sheep) used in our immunization strategy have been previously assessed in other sheep immunization assays and have been shown to be safe and efficient against RVFV [ 61 , 65 ]. These doses are below those used in human studies where even doses of 10 11 viral particles have been used for vaccines based on ChAdOx1 [ 66 ]. The augmented antigenic load has been suggested to affect qualitative aspects of CD8+ T-cell memory/effector responses [ 67 , 68 ] and, despite our results indicate that sheep immunized with ChAdOx1/MVA-NS1 were protected against BTV-4M infection, it would be interesting to analyze whether higher doses of vaccine are still safe for ruminants and completely reduce viremia after BTV infection.…”

Uncovering drivers of dose-dependence and individual variation in malaria infection outcomes

“…Conversely, it has been shown that higher doses trigger distinct, and sometimes more robust, activation of innate and adaptive immune pathways [25][26][27][28]. From an applied perspective, a better understanding of the immunogenic dose-response relationship is pertinent for optimising vaccine dosing to ensure improved safety and efficacy [21,[29][30][31]. However, because the functional output of immune activities (e.g., the rate of immune-mediated iRBC clearance) is Exchange Award).…”

Establishing a Robust Manufacturing Platform for Recombinant Veterinary Vaccines: An Adenovirus-Vector Vaccine to Control Newcastle Disease Virus Infections of Poultry in Sub-Saharan Africa

“…Adenovirus vectors are known to induce strong humoral, mucosal, and cellular immune responses to the encoded antigens. Based on data generated in numerous clinical protocols, adenovirus vectors are considered very effective vectored vaccines [ 43 , 44 ] and their mass production has been previously documented in an important number of studies [ 20 , 45 , 46 , 47 ], seeking significant improvements to reduce the cost of goods and to achieve economical viability. In this study, the production process supported cell growth of HEK293 cells to a density over 4.5 × 10 6 cells/mL during the virus production phase, in which high levels of volumetric and specific cell production yields were achieved.…”

“…It is interesting to note that no hemagglutination inhibition titers were detected in the chickens fully protected by vaccination. This protection could have been mediated by antibodies produced against the F protein that neutralize the virus by binding and preventing attachment to the host cells [ 43 , 54 , 55 ]. This reinforces a key role of the F antigen in its ability to induce a sufficiently potent response against NDV.…”