Science - USA (2022-04-29)

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gens than haemagglutinin, this would also

simplify the manufacturing process ( 7 ).

However, although longer-duration im-

munity could have important public health

benefits, it could also pose important con-

siderations for manufacturers. For example,

comparing a vaccine that needs to be ad-

ministered every year against one that is

only required every 5 years, over time the

former would have five times the potential

market as the latter. This simple compari-

son could be moderated by any increase in

demand associated with longer-duration

immunity; understanding such effects will

be important in planning for manufactur-

ing and distribution of future vaccines.

Vaccines conferring longer-duration im-

munity will also require careful planning

in their manufacturing and deployment.

As an extreme but illustrative example, if a

country’s immunization program involves

mass vaccination every 5 years, this would

naturally lead to boom-and-bust cycles in

demand; in intervening years, manufactur-

ers will need to repurpose production lines

for other vaccines. Where different coun-

tries follow different immunization pro-

grams, this could lead to demand volatility,

potentially compromising sustainability

for manufacturers. Alternative immuni-

zation schedules could help to smooth

demand over time, such as “cohort” vac-

cination strategies focused each year on

5-year-olds, 10-year-olds, and so on. Such

strategies are routinely used for childhood

vaccines such as DTaP against diphtheria,

tetanus, and pertussis.

Other approaches to address demand

volatility could include centralized purchas-

ing mechanisms to coordinate and stag-

ger vaccine procurement among different

countries, helping to create a market that

remains stable over time. Examples of such

mechanisms include the Pan American

Health Organization (PAHO) revolving fund

and the United Nations Children’s Fund

(UNICEF) Supply Division, which acts on

behalf of Gavi, the Vaccine Alliance.

GLOBAL PRODUCTION CAPACITY

At present, production of influenza vaccines

is heavily concentrated in high-income set-

tings. Manufacturers in high-income coun-

tries, accounting only for 16% of the global

population, account for an estimated 69%

of seasonal influenza vaccine production

and 80% of potential pandemic vaccine

production ( 8 ). These disparities mirror

global imbalances in the uptake of influ-

enza vaccines: Although the United States

has among the world’s largest coverage of

routine influenza vaccination as a propor-

tion of its population, uptake is much more

limited in India and other low- and middle-

income countries (LMICs). Reasons for

such low uptake ( 9 ) include lack of aware-

ness of the disease burden of influenza, as

well as the need to vaccinate annually, and

the cumbersome process of deploying vac-

cines that must be reformulated regularly

as the virus evolves. It is likely that a future,

broadly protective vaccine, with similar ef-

ficacy to that of current vaccines but offer-

ing multiyear protection while not needing

to be reformulated so often, would address

some key issues for uptake in LMICs.

Alongside increasing uptake to facilitate

the emergence of a global market, we ar-

gue that there will be several benefits to

promoting regional production to meet

local needs while leveling current imbal-

ances in global production capacity. From

an epidemiological perspective, future in-

fluenza vaccines could be used strategically

for pandemic preparedness and response.

As demonstrated during the COVID-19

pandemic, global supply of pandemic vac-

cination is not always aligned with global

need because countries prioritize coverage

among their own populations. If increased

future demand for new influenza vaccines

facilitates the establishment of regional

production capacity to meet local needs,

this distributed capacity will be valuable

in ensuring that all countries have the

necessary access to vaccines for pandemic

response. This benefit need not be limited

to influenza pandemics, with new technolo-

gies such as mRNA and viral vectors be-

ing applicable to other infections as well.

As long as regional vaccine manufacturing

sites are sufficiently flexible, they could be

deployed rapidly against a wide array of

emerging infections ( 10 ). New initiatives al-

ready underway to expand manufacturing

capacity for COVID-19 and other vaccines

in Africa and elsewhere could represent im-

portant steps toward equitability in global

pandemic preparedness.

From an economic perspective, for both

seasonal and pandemic vaccination, an ex-

panded market with the right number of

manufacturers allows production to benefit

from economies of scale ( 11 ), potentially al-

lowing lower vaccine prices at least for the

poorest countries. A large, globally distrib-

uted market could establish a virtuous cycle

by reducing local costs of broadly protec-

tive vaccines, which in turn could facilitate

increased uptake (and consequently com-

mercial attractiveness). Gavi exerted such

effects on the global market for the pen-

tavalent vaccine: Their coordinated market-

shaping initiatives led to more manufac-

turers entering the market, which in turn

reduced vaccine prices ( 12 ).

A much-expanded market could also

lower costs by facilitating entry of new

manufacturers. Currently, only a few low-

or lower-middle-income countries have

capacity to produce vaccines that meet

stringent quality standards [approved by

stringent regulatory authorities or be-

ing World Health Organization (WHO)–

Ye a r s

Duration of protection

Breadth of protection

Narrow Broad

Vaccinated Waned

Months

Strong population immunity

Economics

• Vaccines needing to be updated less often:
  more predictable demand over time


• If increased breadth leads to greater
  demand, consequent increase in market size

Epidemiology

• Vaccines needing to be updated less often:
  simplified annual vaccine recommendations


• Broader, more eective protection against
  pandemic viruses


• For seasonal viruses, smaller protection gap
  to be filled

Economics

• Potential for higher demand
  volatility year-to-year if
  country purchasing is not
  coordinated/staggered


• Potentially reduced market
  size over time

Epidemiology

• For individuals, repeat
  vaccination required less
  frequently over life course


• Impact of annual
  vaccination can be
  amplified by accumulating
  population immunity


• Potential for enhanced
  protection from new,
  pandemic viruses

Economic and epidemiologic considerations

Boxes show key factors associated with improving vaccine performance in terms of duration (vertical axis)

and breadth of protection (horizontal axis).