Retroviral Pseudotypes – From Scientific Tools to Clinical Utility

Abstract

Retroviral pseudotypes are important research and diagnostic tools for basic and clinical virology studies, facilitating the detailed investigation of individual genes, cellular receptors, antibody responses, serosurveillance and antiviral therapies. Importantly, pseudotypes enable the study of highly pathogenic viruses, without the need for high containment. Their use as gene therapy vectors is widely documented, but other uses, once less well known, are becoming more prominent. The substitution of envelope proteins expressed on the virion surface enables pseudotypes to be employed as surrogates for wildtype viruses in antibody neutralisation or antiviral screening assays and for the study of cell–virus receptor interactions. In addition, they are increasingly being utilised as vaccine immunogens, expressing the antigen either on the particle surface or as a transfer gene for cellular expression. These studies demonstrate the potential for using pseudotypes for both scientific and clinical applications. Key Concepts Students will learn: What are retroviral pseudotypes. How they are constructed and titrated. The common elements that comprise a retroviral pseudotype. How retroviral pseudotypes can be used to deliver genes. How they can be used as tools for the study of viral attachment, entry and receptor identification. About using pseudotypes as surrogate viruses in antibody neutralisation assays. The use of pseudotypes to measure vaccine immunogenicity and screen for antiviral activity and resistance. How pseudotypes can be used as experimental vaccines.

Evaluation of a Pseudotyped Virus Neutralisation Test for the Measurement of Equine Influenza Virus-Neutralising Antibody Responses Induced by Vaccination and Infection

“…Pseudotyped viruses presenting the surface proteins of numerous viruses have been exploited for different applications: from basic cell tropism and receptor studies [ 12 , 13 ], through to antiviral screening, serological surveillance [ 14 , 15 ] vaccine efficacy evaluation, and even as vaccine antigens themselves [ 16 , 17 , 18 ]. A major use of PVs is in the sensitive measurement of neutralising antibody responses in sera following natural infection or vaccination.…”

Generation of Arctic-like Rabies Viruses Containing Chimeric Glycoproteins Enables Serological Potency Studies

“…Serological studies are required to define VnAb titres as part of vaccination and antiviral development and treatment schedules, while also allowing surveillance of the epidemiological spread of emerging viruses. As PV incorporate envelope proteins identical to the wildtype virus in their envelope they are antigenically similar, mimic the action of live virus in neutralisation tests and have proven to be a safe, robust and flexible alternative for use in serological assays (Mather et al , 2013; Temperton et al , 2015). The PVNA can be undertaken in containment level 1 and 2 laboratories as it does not require the handling of live virus, as opposed to other rabies virus neutralisation tests.…”

“…Pseudotyped virus (PV), a replication defective viral particle acting as a surrogate for live virus, has been used in a range of applications including serological assays and as vaccine immunogens (Mather et al , 2013; Temperton et al , 2015). The development of a PV neutralisation assay (PVNA) for the measurement of anti-rabies virus neutralising antibodies (VnAbs) in vaccine recipients, along with further large scale in-field sero-surveillance within a developing country has previously been described, providing sensitive and specific results which correlate with live virus assays and distinguishes between lyssavirus species (Temperton et al, 2015; Wright et al, 2008, 2009, 2010). As the use of PV allows neutralisation assays to be undertaken in biosafety level 1 or 2 laboratories, along with having a lower cost implication, the serological study of rabies can be expanded to resource-limited laboratories in regions where the virus is endemic.…”

A review of Phase I trials of Ebola virus vaccines: what can we learn from the race to develop novel vaccines?

“…PVs are chimeric virions, which comprise the structural and enzymatic core of one virus with a heterologous envelope protein, e.g. EBOV glycoproteins [ 47 ]. Typically, retroviruses (lentiviruses and gammaretroviruses) or rhabdoviruses (vesicular stomatitis virus) are used as pseudotype cores.…”