tails, modified nucleotides and optimized ORFs [26]. Complexing the RNA with

protamine can also reduce degradation, while simultaneously improving TLR-

mediated adjuvant activity [18].

Another disadvantage that has been reported with the mRNA vaccines are the

rare occurrences of severe anaphylactic reactions. The source of these reactions is

not entirely certain. However, it is thought to be due to the PEG in the LNP [25].

All severe allergic reactions were seen in patients with previous history of ana-

phylactic reactions and allergic reactions to vaccines [43].

Since the original vaccine development occurred against the wild-type SARS-

CoV-2 virus, there has been much uncertainty as to the efficacy of the vaccines

against the emerging variants. In the case of the PB vaccine, its efficacy against the

alpha, beta, gamma, and epsilon variants was reduced by 2, 6.5, 6.7, and 4-fold,

respectively. Similarly, for the Moderna vaccine, efficacy against the same variants

was reduced by 1.8, 8.6, 4.5, and 2.8-fold, respectively. However, further studies

showed 48.7% (single dose) and 88% (double-dose) efficacy of the PB vaccine

against the delta variant, which is the most widely circulating variant at the time this

chapter was written [12,13]. Therefore, there is clearly very much incentive to

encourage mass vaccination of the completed two-dose regimen. Furthermore, the

very nature of mRNA vaccines allows for very minute modifications of the genetic

sequence to protect against emerging variants. Booster shots can be given annually

since the LNP vector is non-immunogenic and, therefore, the body should not build

an immunity against the vector itself.

12.4.2

VIRAL VECTOR VACCINES

The viral vector technology platform involves using a replication-deficient virus

to act as the delivery vector for a genetic sequence encoding the antigen of in-

terest. See details in Chapter 11. The genetic sequence (usually DNA) is an en-

gineered viral backbone modified to express a transgene of interest; in the case of

a vaccine, the transgene is an antigen. It is important to note that the viral vector

itself is usually not the viral pathogen being targeted by the vaccine. This should

also not be confused with LAVs or IVs, which are also virus-based vaccines, but

in those cases the viral component of the vaccine is the pathogen being targeted

by the vaccine.

The benefit of this technology is that viral vectors can be engineered to speci-

fically target certain types of cells. Furthermore, they can naturally enter the cells

using the virus’s own receptor for infection, resulting in an activation of the im-

mune system and a robust cellular and humoral response [1,44]. Once they enter the

cells, the natural mechanisms of infection result in an efficient translocation of

the genetic material to the nucleus and subsequent transcription and translation of

the antigen [45]. This technology was first developed close to 40 years ago using a

vaccinia viral vector expressing hepatitis B surface antigen for use in chimpanzees

exposed to hepatitis B [46].

Several different viruses have been used as vectors either for vaccine production

or for gene therapy. These include adenoviruses, alphaviruses, vesicular stomatitis

viruses (VSV), herpesviruses, arenaviruses, paramyxoviruses, flaviviruses, etc

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Bioprocessing of Viral Vaccines