entry mechanisms and vaccines. Additionally, pseudotyped viruses have some ap-

plications in the research on viruses with high risk [65].

Another recombinant mode of VSV is generated by replacing the gene encoding

for VSV G by the gene encoding for another viral envelope protein (Figure 11.2).

The rVSV is replication-competent both in vivo and in vitro. Unlike the pseudo-

typed virus which can realize single-step infection, the recombinant VSV can serve

as an authentic tool for viral infection to produce a replication-competent vaccine or

non-neurotropic oncolytic virus (Figure 11.3).

11.3.2.2

VSV As a Vaccine Vector

Many advantages have been demonstrated using vectored vaccines to tackle infectious

diseases in recent years. The proteins expressed by the vectors aim to stimulate a

specific and balanced immune response. Compared with most existing live-attenuated

versions of vaccines, modified viral vectored vaccines serve as an alternative strategy

when tackling high-risk diseases such as HIV and Ebola. VSV-based vaccines possess

many advantages in stability, safety, and efficacy. VSV vector shows high capacity

and stability in insertion of transgenes and relatively low toxicity since they do not

integrate into the host cell genome when replicating. As a rare virus type in humans,

pre-existing immunity for VSV is less an issue than it is for AdV. In addition, the

results from preclinical and clinical studies demonstrate that VSV-based vaccines can

induce strong cellular and humoral immune responses.

The recent VSV success story was the FDA-approved Ebola vaccine using a re-

combinant replication-competent VSV-based vector carrying the glycoprotein of a

Zaire Ebolavirus (ZEBOV), the main antigen of the Ebolavirus [66]. The progress

achieved with rVSV-ZEBOV indicates the potential to use this rVSV vector as a

platform against other emerging viral infections. Recently, three novel rVSV con-

structions have been reported, which harbor distinct glycoproteins of the human

immunodeficiency virus (HIV) [67]. Additionally, several rVSV-based vectored

vaccines are in progress, including vaccines against measles, Middle East respiratory

syndrome (MERS), Lassa fever, and Marburg virus disease [68–71]. Numerous

clinical trials have been initiated with the VSV vector. As shown in Table 11.3,

clinical studies involving VSV were performed to control the diseases in situations of

pandemics or cancers.

Despite some successes, there are two main drawbacks using VSV-based vaccines.

First, the natural VSV is a neurotropic virus. Therefore, the concern of neurotoxicity-

related diseases such as encephalitis raises when using the live replication-competent

virus. Second, when comes to the second dose, the pre-existing immunologic re-

sponse issue occurs because of the administration of the same vaccine vector.

However, research on heterologous prime-boost regimens has had some successes.

11.3.2.3

Cell-Line Selection

The Vero (African green monkey kidney) cells, recommended by the World Health

Organization for human-use vaccine production, are the most widely used con-

tinuous cell line for vaccine production. The original Vero cells are anchorage-

dependent cells. The current rVSV-ZEBOV vaccine is manufactured using adherent

Vectored vaccines

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