Pre-existing immunity against vaccine vectors – friend or foe?

Abstract

Over the last century, the successful attenuation of multiple bacterial and viral pathogens has led to an effective, robust and safe form of vaccination. Recently, these vaccines have been evaluated as delivery vectors for heterologous antigens, as a means of simultaneous vaccination against two pathogens. The general consensus from published studies is that these vaccine vectors have the potential to be both safe and efficacious. However, some of the commonly employed vectors, for example Salmonella and adenovirus, often have pre-existing immune responses in the host and this has the potential to modify the subsequent immune response to a vectored antigen. This review examines the literature on this topic, and concludes that for bacterial vectors there can in fact, in some cases, be an enhancement in immunogenicity, typically humoral, while for viral vectors pre-existing immunity is a hindrance for subsequent induction of cell-mediated responses.

Self-Amplifying mRNA Vaccines

“…However, a significant Self-Amplifying mRNA Vaccines limitation of this approach is interference by antivector immunity, either from previous exposure to live infection (e.g., adenovirus) or by prior immunization (e.g., smallpox). Neutralizing antibody responses directed toward the viral proteins present on the surface of the vector or T cell responses against expressed proteins of the vector can blunt the effectiveness of the vaccine and the ability to obtain useful responses from booster doses (Saxena, Van, Baird, Coloe, & Smooker, 2013).…”

An Overview on Oncolytic Viruses as Cancer Therapy

“…The use of vectors of non-canine origin like e.g., MV or removing key neutralizing epitopes on the surface of viral capsid proteins might help to avoid pre-existing immunity. In addition, intratumoral or mucosal virus application or administration of higher virus doses could also be a solution for pre-existing immunity problems [60].…”

Cold-adapted influenza viruses as a promising platform for viral-vector vaccines

“…The potential advantages include strong immune responses, capacity for large gene inserts, genetic stability and good expression of the constructs, and the availability of various strains. Among the potential disadvantages are preexisting immunity in the population because of widespread viral infection or immunization campaigns, immunogenicity of vector itself, and the pathogenic and tumorigenic potential of viruses with a doublestranded DNA genome [5,6]. In addition, it is sometimes impossible to find a proper balance between attenuation, immunogenicity, and growth properties of a viral vector, as was demonstrated in preclinical studies of engineered vectored vaccines based on vesicular stomatitis virus [7].…”