a century. IVs have been successfully used against polio, hepatitis A, rabies, and

influenza. Similarly, LAVs have been used against measles, mumps, rubella, var-

icella, rotavirus, polio, yellow fever, and influenza [17,19]. Because the development

of whole virus vaccines does not require very much knowledge of the viral compo-

nents and involves mainly cell-culture, this method of vaccine production, especially

IVs, can be relied upon in circumstances when a new pathogen emerges, and a

vaccine is rapidly needed [1]. However, since their production involves the propa-

gation of live virus, they must be manufactured in biosafety level 3 facilities [56].

There are several IVs that have been developed against SARS-CoV-2, including

two vaccines from the Chinese biotech companies Sinovac and Sinopharm, as well

as a candidate from the Indian Bharat Biotech. Both Chinese vaccines use Vero

cells to propagate the virus. Sinopharm’s vaccine, also known as BBIBP-CorV, was

designed and produced as follows: several different strains of SARS-CoV-2 were

isolated from the bronchoalveolar lavage samples of hospitalized patients. These

strains were then grown in Vero cells and serially passaged over 10 generations in a

basket reactor. The strain with the highest replication and viral yields was selected,

because highly efficient proliferation and high genetic stability are key features for

the development of IV vaccines [57]. The selected strain, known as HB02, was

sequenced and compared to other global strains of SARS-CoV-2 demonstrating

sequence homology and 100% homology of the S-protein. It was, subsequently,

purified and inactivated with ß-propiolactone at a ratio of 1:4000 at 2–8°C [57].

Phase 3 trial results for the Sinopharm vaccine showed efficacies of 79.34% [56].

Sinovac’s vaccine, also known as CoronaVac, was propagated in African green

monkey kidney cells (WHO Vero 10–87 cells). At the end of the incubation period,

the virus was harvested, inactivated with β-propiolactone, concentrated, purified,

and then adsorbed onto aluminium hydroxide. The aluminium hydroxide complex

was then diluted in sodium chloride, phosphate-buffered saline, and water before

being sterilized and filtered for injection [58,59]. Phase 3 trial results for the

Sinovac vaccine showed varying results ranging from efficacies of 50.7% in Brazil

to 83.5% in Turkey [60].

12.4.4

PROTEIN SUB-UNIT VACCINES

Protein sub-unit vaccines have been successfully used for many decades. They

consist of antigenic proteins produced by the purification of specific viral proteins

or via the production of recombinant proteins in host cells [4]. They may be pro-

duced using bacterial, yeast, insect, or even mammalian cells depending on the need

for specific post-translational modifications [9]. They are widely used due to their

high safety profiles with little adverse effects and because they do not include whole

viruses, they are safe for use in immunocompromised individuals. Furthermore,

from a production standpoint, they are advantageous since they do not require the

handling of live viruses and are readily scalable for mass production at GMP

standards [26]. Further, their distribution is not as dependent on cold-chain systems

as some of the other vaccine platforms. However, their manufacturing processes

may be expensive in the event they require animal cell expression systems [4].

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Bioprocessing of Viral Vaccines