vectors covers the use of low-pathogenicity viruses genetically modified with the

purpose of vectoring the expression or display of the dominant antigens related to the

targeted infectious diseases to induce a humoral and cellular response.

Both AdV- and VSV-based vectors led to the development of approved vaccines

for human use against emerging and re-emerging infectious diseases, especially

different serotypes of AdV-vectored vaccines in the case of the COVID-19 pan-

demic and VSV-vectored vaccine in the case of the Ebola epidemic [1,2]. These two

viral vectors, representative of the classes of non-enveloped (AdV) and enveloped

viruses (VSV) as well as DNA (AdV) and RNA (VSV) viruses, involve a broad

range of biological and structural properties that would determine their modes of

production, purification, and formulation [3,4].

Apart from AdV- and VSV-vectored vaccines exemplified in this chapter, many

other viral vectors have been developed for vaccination including yellow fever

virus, poxvirus, paramixovirus, and alphavirus and they have been used for control

of infectious diseases [5–8]. Chimeric vaccines, such as yellow fever virus-based

vaccines including Japanese encephalitis and Dengue vaccines from Sanofi-Pasteur

would fall under the general definition of vectored vaccines [9,10]. The yellow

fever virus backbone is modified to express antigens related to the Japanese en-

cephalitis virus infection. Similarly, the tetravalent dengue vaccine uses the yellow

fever virus backbone to express proteins from different serotypes of the dengue

virus. These vectored vaccines have been evaluated for safety and efficacy in nu-

merous clinical trials at different phases, as shown in Table 11.1.

From the perspective of design and processing, some of the vectors and particu-

larly adenovirus-vectored vaccines benefited from extensive background knowledge

and expertise originally developed within the field of gene therapy and virotherapy

extending the vaccinology application field to oncotherapy and therapeutic vaccines.

Replication-defective vectors are mostly used in oncotherapy; however, replication-

competent viruses such as reovirus and NDV are currently used in many clinical trials

in virotherapy targeting specifically tumor cells [11,12].

11.2

ADENOVIRUS-VECTORED VACCINES

AdV vectors derive from Adenoviridae, a diverse family of non-enveloped, icosahedral,

double-stranded DNA viruses [3]. The first use of AdV as a vaccine vector can be

traced back to the 1980s [13]. Since then, AdV vectors have shown great promise and

consequently have been extensively explored. AdV vectors hold attractive advantages

as vaccine vectors including safety, stability, and efficacy. As a replication-defective

vector, there is no serious risk of horizontal transmission when using AdV. The genome

of AdV vectors does not integrate into the chromosome of the host cells, which avoids

the risk of insertional mutagenesis [14]. AdV vectors possess a robust transgene ex-

pression ability that can be strengthened by strong heterologous promoters. AdV vectors

can be efficiently produced in large-scale cell cultures. AdV can infect a wide range of

vertebrates, including humans and non-human primates. AdV vectors can activate

strong immunoreaction when administered via intramuscular or mucosal routes.

Additionally, AdVs were the first viral gene transfer vectors developed for use in

humans due to their high transduction efficiency and relatively low virulence. The

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Bioprocessing of Viral Vaccines