manufacturers have a 6-month window to produce and provide vaccines for vac-

cination campaigns around the world [15,16]. Numerous factors may challenge this

production timeline: the generation of egg-adapted virus seed stocks and a con-

tinuous egg supply, as ~80% of influenza vaccines are produced in embryonated

hens’ eggs [17]; the lack of specific reagents for vaccine quantification; the need for

full characterization of the product and the fulfilment of regulatory aspects [18,19].

In spite of WHO’s extensive efforts to increase global influenza vaccine production

to respond to the threat of a global pandemic, manufacturing capacity is still not

sufficient. According to Sparrow, et al. [17], an estimated 8.31 billion doses could

be produced in a 12-month period by current active manufacturers, an estimation

made based on various assumptions such as a sufficient supply of eggs and other

reagents, which might not be the case if manufacturers are in the middle of seasonal

vaccine production. Furthermore, multiple doses might be required for vaccine

effectiveness, and some pandemic strains, such as the H5N1, have already shown

suboptimal production in egg-based systems [20].

9.4

INFLUENZA VACCINES

Vaccination is the most cost-effective and efficient way to minimize the impact of flu

outbreaks in society [21]. However, the influenza disease can also be treated with the

use of antiviral drugs, although resistance to some of these drugs has already been

reported [22]. Tables 9.1 and 9.2 summarize the different types of vaccines and an-

tiviral drugs, respectively, available for influenza prevention and treatment.

Three types of vaccines are currently approved and available on the market for

influenza: inactivated influenza vaccine (IIV), live attenuated influenza vaccine

(LAIV), and recombinant vaccine (RV). Manufacture of IIVs and LAIVs, which

together correspond to almost 90% of production capacity [17], relies on the gen-

eration of master viral seed stocks. As some influenza strains present limited yields

when produced in vitro, master virus stocks are composed of high growth re-

assortants (HGR), a modified virus expressing the antigenic proteins HA and NA

from the targeted strain within the backbone of a high growth strain such as the A/

PR/8/34 H1N1. While critical for egg-based influenza vaccine production, it is yet

not clear if HGRs are necessary for cell-culture−based vaccine manufacturing, with

evidence suggesting no significant improvement in virus yields for cell-base

TABLE 9.1

Different types of Influenza vaccines available in the market

Vaccine type

Composition

% of global capacity

(seasonal) [ 17]

Inactivated influenza

vaccine (IIV)

trivalent, quadrivalent,

adjuvanted

89.6%

Live attenuated vaccine (LAIV)

trivalent, quadrivalent

5.0%

Recombinant vaccine (RV)

trivalent, quadrivalent

5.4%

228

Bioprocessing of Viral Vaccines