INSIGHTS | POLICY FORUM
464 29 APRIL 2022 • VOL 376 ISSUE 6592 science.org SCIENCE
prequalified]. Use of newer platforms such
as recombinant proteins, adenovirus vec-
tored, or lipid-encased mRNAs is largely
limited to India and China ( 13 ). Developing
such manufacturing capacity in other coun-
tries requires intensive “soft” infrastructure
in the form of chemistry, manufacturing,
and control (CMC) staff and “hard” infra-
structure in the form of new equipment for
manufacturing and laboratory and analyti-
cal testing. New manufacturers who invest
in this infrastructure are likely to operate
on a smaller scale compared with that of
manufacturers in India and China and are
therefore likely to see increased costs of
production. A much expanded market could
therefore facilitate the entry of these manu-
facturers by offsetting these increased costs.
ROLES FOR DONORS AND POLICY-MAKERS
Catalyzing the development of such a global
market is likely to require effective partner-
ships between industry, policy-makers, and
academia. There will be a critical role for
international agencies and donors to play,
not only in the research and development of
new vaccines but also in their manufactur-
ing and distribution.
Mechanisms such as advance market
commitments could attract greater industry
participation in the process of vaccine de-
velopment. To the extent that new vaccines
depend on new technologies, they will also
require new mechanisms for evaluation of
their performance. Pathways for regulatory
approval will need to be updated, to incor-
porate these new mechanisms. A global
market will require updates to regulatory
approval to be coordinated at a global level
to facilitate the deployment of new vaccines
worldwide. It is likely that licensure of fu-
ture vaccines will proceed in steps rather
than leaps—for example, with breadth and
duration of protection being steadily im-
proved with each successive generation of
vaccine development. Therefore, although
“target product profiles” that identify ideal
characteristics for future vaccines would of-
fer helpful reference points in vaccine de-
velopment and international regulatory co-
ordination, it will be equally important for
donors and international agencies to plan
how best to recognize and reward interme-
diate stages toward achieving those ideals.
Once vaccines are developed and licensed,
there will be a need for further interventions
in their distribution, both on the demand side
and the supply side. Creating a sustainable
demand side requires mechanisms for long-
term public funding of vaccine purchases by
country governments, global coordination of
influenza vaccines for LMICs, and if needed,
using pooled procurement structures such
as UNICEF and the PAHO revolving fund
for LMIC purchase of influenza vaccines.
On the supply side, there will be a need
for concessional loans and other forms of
investment from development finance insti-
tutions (such as the International Finance
Corporation) to finance the capital expen-
diture for setting up new sites in LMICs for
influenza vaccine manufacturing.
In addition to plant and equipment and
technical know-how, vaccine manufactur-
ing—especially using newer cell-based plat-
forms and mRNA—requires many complex
input components, some of which have
limited sources of supply. A globally coor-
dinated mechanism is needed to manage
the material, know-how, and other criti-
cal resources required for the global mar-
ket to operate. The WHO Global Action
Programme initiative offers an example of
such a coordinated mechanism, in the con-
text of current influenza vaccines ( 8 ). As
new technology platforms emerge, new co-
ordination architectures may have to be de-
signed to accommodate their deployment.COMPARISONS WITH OTHER INFECTIONS
To illustrate how the value propositions
for future vaccines for other diseases could
depend on the disease in question, we
consider two other respiratory diseases,
COVID-19 and tuberculosis (TB).
Like influenza, coronaviruses are estab-
lished in the human population and have
proven pandemic potential. Although li-
censed vaccines to SARS-CoV-2) raise im-
munity to the surface spike protein, there
is increasing interest in targeting more
conserved antigens to raise more broadly
protective immunity. Although it will be
challenging to achieve a truly universal
coronavirus vaccine, recent work has shown
promising signs of raising broad protection
against sarbecoviruses [for example, ( 14 )], a
lineage to which SARS-CoV-2 belongs, along
with SARS-CoV-1, which first emerged in
humans in 2003. Owing to the global bur-
den of SARS-CoV-2, and the need to pro-
tect against future coronavirus pandemics,
many of the considerations raised here (see
the figure) would apply to future corona-
virus vaccines as well. However, endemic
coronaviruses have only modest contribu-
tion to the burden of respiratory illness,
particularly in comparison with seasonal
influenza; SARS-CoV-2 may, over time, simi-
larly transition to being an endemic virus
causing mostly mild illness. Accordingly,
compared with influenza vaccines, the pub-
lic health value proposition of future coro-
navirus vaccines may have a greater empha-
sis on pandemic protection than on routine
immunization. However, a sizable burden
of “long covid” after endemic SARS-COV-2
infection could alter this balance.For TB, the world’s leading cause of death
from infectious disease, the public health
case for new, effective vaccines is clear.
However, with global TB burden overwhelm-
ingly concentrated in LMICs, the potential
market for future TB vaccines is not as com-
mercially promising as for other vaccines.
Hence, despite a recent phase 2b trial of the
M72/AS01e vaccine showing promising signs
of efficacy ( 15 ), it has been challenging to
find industry partners who are willing and
capable of taking this candidate forward to
phase 3 trials. The Bill and Melinda Gates
Medical Research Institute (Gates MRI) will
support clinical trials of the vaccine, having
recently acquired the license from Glaxo
SmithKline. Even though future vaccines
against TB and other diseases of poverty may
well benefit from new technologies deployed
against COVID-19, international public
health agencies and donors will need to play
an even more active role than in the context
of influenza vaccines.
A globally distributed market for influenza
vaccines, supported by regional production
capacity to meet regional need, would be one
way of aligning public health, supply resil-
ience, and commercial interests but will not
necessarily develop on its own; international
public health agencies and donors will have
a key role to play, in catalyzing the creation
of such a truly global system. jREFERENCES AND NOTES- M. T. Osterholm, N. S. Kelley, A. Sommer, E. A. Belongia,
Lancet Infect. Dis. 12 , 36 (2012). - R. Subramanian, A. L. Graham, B. T. Grenfell, N.
Arinaminpathy, PLOS Comput. Biol. 12 , e1005204
(2016). - S. Sridhar et al., Nat. Med. 19 , 1305 (2013).
- R. D. Antrobus et al., Mol. Ther. 22 , 668 (2014).
- R. Nachbagauer et al., Nat. Med. 27 , 106 (2021).
- D. M. Weinberger, R. Malley, M. Lipsitch, Lancet 378 ,
1962 (2011). - L. J. Kornish, R. L. Keeney, O p e r. Re s. 56 , 527 (2008).
- E. Sparrow et al., Va c c i n e 39 , 512 (2021).
- J. R. Ortiz, K. M. Neuzil, J. Infect. Dis. 219 (Suppl_1), S97
(2019). - P. Yadav, A. Desir, INSEAD Knowl. 3 November 2021;
https://knowledge.insead.edu/operations/boosting-
vaccine-production-needs-the-right-degree-of-flexibil-
ity-17621. - S. Plotkin, J. M. Robinson, G. Cunningham, R. Iqbal, S.
Larsen, Va c c i n e 35 , 4064 (2017). - M. Malhame et al., Va c c i n e X 2, 100033 (2019).
- National Academies of Sciences, Engineering, and
Medicine, National Academy of Medicine, Globally
Resilient Supply Chains for Seasonal and Pandemic
Influenza Vaccines (The National Academies Press, 2021). - D. R. Martinez et al., Science 373 , 991 (2021).
- D. R. Tait et al., N. Engl. J. Med. 381 , 2429 (2019).
ACKNOWLEDGMENTS
The authors thank S. Suvanand and D. Lewinsohn for helpful
comments on future TB vaccines. In addition to the funding
for this work from FluLab, C.M.S.-R. acknowledges support
from a Postgraduate Doctoral Scholarship of the Natural
Sciences and Engineering Research Council of Canada and
from a Charlotte Elizabeth Procter Fellowship of Princeton
University. N.A. acknowledges support from the MRC Centre
for Global Infectious Disease Analysis (reference MR/
R015600/1).
10.1126/science.abm8894