10. Viral vector vaccines
Engineered vectors are a novel generation of vaccines that invoke
recombinant DNA technology to insert the encoding gene of pathogen
antigens into the genome of bacterial or viral vectors [100].
Following vaccination, the recombinant vector sometimes multiplies in
the host body and induces potent B and T cell immune responses by
expression and processing of pathogen antigens (Fig. 2) (Table
3). Escherichia coli, adenovirus (Ad) and poxvirus are among the most
widely used bacterial and viral vectors, respectively. Manufacturing of
vaccines against meningococcus, hepatitis B virus (HBV), human
papillomavirus (HPV), haemophilus influenza type b (Hib) and pertussis
are the most common examples of vector utilization in vaccine design
[27]. Viral vectors based on their ability to propagate in the host
cells are divided into two main categories including non-replicating and
replicating vectors. The non-replicating vectors have lost their
reproductive ability by deleting a certain part of their genome, but
retain the capacity of expressing a target gene. These are account for a
large share of vaccine production and are primarily designed based on
adenovirus as well as adeno-associated virus (AAV), Modified Vaccinia
virus Ankara (MVA), influenza, parainfluenza and Sendai viruses [60,
101, 102]. Most of these vectors are injected intramuscularly and
induced passable specific cellular and humoral immune responses.
Besides, high titers of these vectors can be achieved by the laboratory
instruments [101]. On the other hand, replicating vectors compose of
attenuated or vaccine type viruses that expressing the foreign antigen
and proliferate somewhat in the host cells. Animal viral vectors are
more popular in this case because of limited replication in human hosts
and significant innate immune induction due to specious heterogenicity.
Besides, mucosal administration of these xenogen vectors will
significantly stimulate mucosal immunity, which is important in
combating mucosal viruses such as SARS-CoV2 [103]. Currently, two
human vaccines based on viral vectors have been reported to fight Ebola
and cancer maladies. This platform of the Ebola vaccine has been
extensively studied and can be used as a model for other infectious
diseases, while the safe anti-cancer vector vaccine induced strong T
cell responses without the need of adjuvants [104, 105]. Meanwhile,
some viral vectors, such as Ad5 and ChAd, are preferred for use in
SARS-COV2 researches because they provide acceptable protection with a
single dose and demonstrate natural tendency for the respiratory mucosa
[49]. In addition, this technology is available for mass production
of clinical grade vaccines. Overall, 41 viral vector vaccine candidates
against COVID-19 are under preclinical stage and 16 candidates are
undergoing clinical trials [52] while only 3 vaccines based on
ChAdOx1, vesicular stomatitis virus (VSV) and Ad26 viral vectors have
been selected for the public–private Operation Warp Speed (OWS)
partnership of the US [106]. Viral vector vaccines with attenuated
or defective replication capacity against SARS-CoV2 are Ad5 or
MVA-dependent and mainly express
the epitopes of S protein and related RBD domain. Although the viral
vectors with suitable replicative competency are more common with
vaccine type of human (influenza and measles (or zoonotic (VSV)
pathogens. It is important to note that in some cases, due to previous
exposure of immune system to similar strains during a person’s lifetime
or prime-boost regimen, the viral vector is disarmed before any action
and does not work as well as it should. This can be overcome by using
animal-derived viral vectors such as ChAd or infrequent human vectors,
against which the probability of previous immunity is very low or near
to zero [49]. Besides, different priming and boosting vectors
greatly reduce the risk of previous vector immunity. Also, some viral
vectors, such as AAV, are weak stimulant of immune responses and mostly
used in human studies [103].
As of February 9, 2021, four adenovirus-based vector vaccines including
Ad5-nCoV (replication-defective
Ad5 containing S protein) by CanSino Biologics,
Sputnik V or Gam-Covid-Vac
(combination of Ad5 and Ad26 containing S protein) by Gamaleya Research
Institute, Ad26.COV2.S (optimized Ad26 containing S protein) by Johnson
& Johnson and AZD1222 (replication-deficient ChAdOx1 containing S
protein) by AstraZeneca company and university of Oxford are going
through phase ΙΙΙ clinical trials, and the Ad5-nCoV and Sputnik V have
received licenses of limited and early use in China and Russia,
respectively. Also, intranasal spray of influenza vector-based-RBD
vaccine, DelNS1-2019-nCoV-RBD- OPT1, as a phase ΙΙ clinical trial is
under investigation. Currently, an innovative COVID-19-artificial
antigen presenting cell (aAPC) vaccine was also developed by Shenzhen
Geno-Immune Medical Institute using the replication-competent NHP/TYF
lentiviral vector system in order to expressing the immunomodulatory and
viral genes in modified APCs. By doing so, T cells are likely to be
significantly activated, although the efficacy and safety of this
vaccine in a phase Ι clinical trial are being investigated. In addition,
a similar vaccine, named LV-SMENP-DC, is being evaluated in a phase Ι/ΙΙ
trial using non-replicating lentiviral vectors from the same company
that express the COVID-19 SMENP mini-gene along with immunomodulatory
genes in DC cells. However, other similar researches based on
replication-incompetent vectors including simian adenovirus (SAV), MVA,
Ad5 are in development [52].