and Ad26). Phase 3 trials reported an efficacy of 91.6% after two doses with 100%

protection against moderate to severe COVID-19 infection [54]. The vaccine re-

sulted in activation of both humoral and cellular immunity, 42 and 28 days after the

first dose, respectively [54].

In terms of efficacy against variants, it was found to vary among the different

vaccines and variants. For example, the J&J vaccine was shown to be effective

against all variants including the delta variant, whereas the OA vaccine has shown

mixed results ranging from complete immune escape from the beta variant to 67%

efficacy against the delta variant [2,13,55].

12.4.3

WHOLE VIRUS VACCINES

The next class of vaccines to discuss is the whole virus vaccines consisting of

inactivated vaccines and live attenuated viruses. IVs are whole viruses that have

been inactivated by heat or chemical treatment [18]. See Chapter 9 for more details

on an inactivated vaccine against influenza virus infections. Vaccines against polio

infections, another example of IVs, are mostly produced using Vero cell lines to

propagate the live virus for several generations and are subsequently harvested,

purified and then inactivated [9]. Because they are inactivated, they cannot cause an

infection, and therefore have a high safety profile. While formaldehyde was tra-

ditionally used to inactivate the pathogens, it is now known to damage or alter the

antigenic properties of proteins potentially leading to altered immune responses [9].

Therefore, β-propiolactone is now commonly used as an inactivating agent.

LAVs differ in that they are weakened forms of the virus that can replicate to a

limited extent, but are unable to cause the actual disease [18]. LAVs are weakened

through repeated passage in cell-culture [4]. Because both IVs and LAVs use whole

viruses, they lead to a polyclonal response to multiple viral proteins, rather than

single antigen-based vaccines. Therefore, the extensive T-cell and B-cell response

makes it unlikely for the virus to mutate enough to render the vaccine ineffective

[17]. However, despite this polyclonal response, IVs have been shown to have low

to moderate immunogenicity requiring the use of adjuvants or multiple dosing to

elicit a robust immune response. They have also been shown to enhance disease

pathology through ADE [4,26].

LAVs induce stronger immune responses than IVs due to their ability to replicate

and mimic a natural infection. They induce strong immune responses at mucosal

surfaces as well, which is vital for respiratory pathogens. Furthermore, because the

vaccine components can replicate, they can spread to non-vaccinated individuals, thus

extending the impact of vaccination to the whole population [19]. However, before a

LAV can be used, it must be shown that it cannot revert to virulence as this can

have devastating effects. In fact, this phenomenon was seen in the oral polio LAV

vaccine, resulting in paralysis in 1 out of 2 million patients [19]. Furthermore, they have

limited use in the immunocompromised and pregnant women due to the weakened

immune systems of these populations. This danger of reversion to pathogenesis also

means that LAVs are usually not good vaccine strategies for highly pathogenic viruses.

Both IVs and LAVs are relatively simple and cost-effective to make, which ex-

plains their ubiquitous use. IVs and LAVs have been used for many vaccines for over

COVID-19 vaccines

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