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A Strategic Approach To COVID-19 Vaccine R&D: Lawrence Corey, John R. Mascola, Anthony S. Fauci, Francis S. Collins
A Strategic Approach To COVID-19 Vaccine R&D: Lawrence Corey, John R. Mascola, Anthony S. Fauci, Francis S. Collins
A public-private partnership and platform for harmonized clinical trials aims to accelerate licensure and
distribution.
There is an unprecedented need to manufacture and dis- ies to the spike protein, have been shown to be protective
First release: 11 May 2020 www.sciencemag.org (Page numbers not final at time of first release) 1
symptomatic disease, especially amelioration of disease se- been suggested. Such experiments, if designed to define po-
verity, including the frequency of disease requiring high- tential immune correlates or winnow out less effective vac-
intensity medical care with some assessment of a decrease cine approaches, may have utility. However, this approach
in hospitalization. This requires the close evaluation of the has shortcomings with respect to pathophysiology and safe-
effect of vaccination on the severity of COVID-19 disease in ty (12). Although the risk of severe disease or death in young
a wide variety of epidemiological and medical settings healthy individuals from COVID-19 is quite low, it is not
among both younger and elderly populations as well as un- zero, and we do not yet have proven effective therapies for
derserved minorities. All of these issues need to be evaluat- COVID-19 to rescue volunteers with complications from
ed in the context of these initial efficacy trials. Achieving such a challenge. It is likely that a SARS-CoV-2 challenge
these endpoints could also be associated with reduced strain will, by design, cause mild illness in most volunteers
transmissibility on a population basis. and thus may not recapitulate the pulmonary pathophysiol-
Primary endpoints that involve reduction of disease re- ogy seen in some patients. Moreover, partial efficacy in
quire greater numbers of enrollees into trials, given that young healthy adults does not predict similar effectiveness
asymptomatic infection is estimated to be 20 to 40% of total among older adults with major cofactors associated with
cases of COVID-19 (8). Initial efficacy trials may then re- COVID-19 disease, nor would it prove reduction of transmis-
First release: 11 May 2020 www.sciencemag.org (Page numbers not final at time of first release) 2
safety while addressing the lack of commercial experience of generating surrogate markers that ultimately speed licen-
with them. sure and an overall comparison of efficacy. A common Insti-
Traditional recombinant protein technology can be used tutional Review Board as well as a common cross-trial Data
to express the spike protein (e.g., Sanofi, Novavax), and alt- and Safety Monitoring Board (DSMB) should be used so
hough the time to establish cell lines needed for manufac- that the regulatory framework for the entire enterprise is
turing is longer than for nucleic acid vaccines, there is a coordinated and the regulatory agencies and the public can
robust commercial experience with protein and protein par- make objective assessment of the effect sizes between ap-
ticle vaccines, including licensed vaccines for hepatitis B, proaches. As vaccine candidates are poised to enter phase 1,
human papillomavirus, varicella zoster, and influenza. Pro- the collective planning for phase 3 must be undertaken. Alt-
tein vaccines will require a potent adjuvant, which can be hough much of this focus is on trials in the United States,
critical for inducing a predominantly TH1-type immune re- the COVID-19 Prevention Networks established under the
sponse; however, the availability of certain adjuvants may ACTIV program have a global focus, and coordination with
be limited. Viral vector vaccines encode the viral gene of the World Health Organization, Coalition for Epidemic Pre-
interest into one of several well-characterized vectors, in- paredness Innovations, and other global philanthropic part-
cluding adenovirus (Ad) and vesicular stomatitis virus ners must also occur.
First release: 11 May 2020 www.sciencemag.org (Page numbers not final at time of first release) 3
factories can be developed to sustain production, there is an 9. S. M. Kissler, C. Tedijanto, E. Goldstein, Y. H. Grad, M. Lipsitch, Projecting the
immediate need to fund the necessary biomanufacturing transmission dynamics of SARS-CoV-2 through the postpandemic period.
Science 368, eabb5793 (2020). doi:10.1126/science.abb5793 Medline
infrastructure, including the fill/finish steps that provide
10. W. Liu, A. Fontanet, P.-H. Zhang, L. Zhan, Z.-T. Xin, L. Baril, F. Tang, H. Lv, W.-C.
vialed vaccine products for distribution. Cost, distribution Cao, Two-year prospective study of the humoral immune response of patients
system, cold chain requirements, and delivery of widespread with severe acute respiratory syndrome. J. Infect. Dis. 193, 792–795 (2006).
coverage are all potential constriction points in the eventual doi:10.1086/500469 Medline
delivery of vaccines to individuals and communities. All of 11. T. Bedford et al., Cryptic transmission of SARS-CoV-2 in Washington State.
these issues require global cooperation among organizations medRxiv 2020.04.02.20051417 [preprint]. 16 April 2020.
involved in health care delivery and economics. 12. S. K. Shah, F. G. Miller, T. D. Darton, D. Duenas, C. Emerson, H. Fernandez Lynch,
E. Jamrozik, N. S. Jecker, D. Kamuya, M. Kapulu, J. Kimmelman, D. MacKay, M. J.
To return to a semblance of previous normality, the de- Memoli, S. C. Murphy, R. Palacios, T. L. Richie, M. Roestenberg, A. Saxena, K.
velopment of SARS-CoV-2 vaccines is an absolute necessity. Saylor, M. J. Selgelid, V. Vaswani, A. Rid, Ethics of controlled human infection to
To achieve this goal, all the resources in the public, private, study COVID-19. Science 10.1126/science.abc1076 (2020).
and philanthropic sectors need to participate in a strategic doi:10.1126/science.abc1076
manner. The ACTIV public-private partnership and collabo- 13. K. A. Dowd, S.-Y. Ko, K. M. Morabito, E. S. Yang, R. S. Pelc, C. R. DeMaso, L. R.
Castilho, P. Abbink, M. Boyd, R. Nityanandam, D. N. Gordon, J. R. Gallagher, X.
rative harmonized efficacy trials are enabling models to
Chen, J.-P. Todd, Y. Tsybovsky, A. Harris, Y. S. Huang, S. Higgs, D. L.
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Downloaded from http://science.sciencemag.org/ on May 16, 2020
The ACTIV model for SARS-CoV-2 vaccine development.
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A strategic approach to COVID-19 vaccine R&D
By Lawrence Corey, John R. Mascola, Anthony S. Fauci and Francis S. Collins
published online May 11, 2020originally published online May 11, 2020
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