Abstract
Adenovirus vectored vaccines are a highly effective strategy to induce cellular immune responses which are particularly effective against intracellular pathogens. Recombinant simian adenovirus vectors were developed to circumvent the limitations imposed by the use of human adenoviruses due to widespread seroprevalence of neutralising antibodies. We have constructed a replication deficient simian adenovirus-vectored vaccine (ChAdOx2) expressing 4 genes from the Mycobacterium avium subspecies paratuberculosis (AhpC, Gsd, p12 and mpa). Safety and T-cell immunogenicity results of the first clinical use of the ChAdOx2 vector are presented here. The trial was conducted using a ‘three-plus-three’ dose escalation study design. We demonstrate the vaccine is safe, well tolerated and immunogenic.
Highlights
Viral vectored vaccines are known to be an effective mechanism to induce cellular responses compared with subunit vaccines and can induce protective T cell responses against intracellular pathogens [1]
Twelve male and female healthy adult volunteers aged 18–50 years were enrolled into 3 groups and received a single dose of ChAdOx2 HAV (CONSORT diagram), using a dose escalation approach as described in the Methods section
Recombinant human and simian adenovirus vectored vaccines have been extensively used in clinical trials of infectious diseases and cancer vaccines and thousands of volunteers have been enrolled in studies of investigational vaccines against Human Immunodeficiency Virus (HIV), Malaria, Tuberculosis, Influenza and, most recently, Ebola [35,44,45,46,47]
Summary
Viral vectored vaccines are known to be an effective mechanism to induce cellular responses compared with subunit vaccines and can induce protective T cell responses against intracellular pathogens [1]. Recombinant viruses are excellent vehicles for vaccine delivery as viral proteins can act as potent adjuvants and can directly infect antigen-presenting cells [2]. Adenoviruses are highly attractive vectors for human vaccination as they possess a stable genome which prevents inserts of foreign genes from being deleted and they can infect large numbers of cells without any evidence of insertional mutagenesis [3]. The ubiquity of human adenovirus infections generates levels of host anti-vector immunity that may limit the utility of this vector [18]. Pre-existing immunity can be circumvented by employing vectors based on closely related simian adenoviruses, which have significantly lower seroprevalence rates in human populations [19,20]. Replication-deficient adenovirus vectors may be produced by removing the E1
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