Introduction
Although the spread of the virus can be mitigated through physical distancing, face coverings, and testing and tracing—and potentially with therapeutics—the risk of outbreaks and disruption to economic and social life will probably remain until effective vaccines are administered to large portions of the global population to prevent hospitalisation and severe disease, and preferably achieve herd immunity to halt transmission of the virus.
Figure 1Four dimensions of an effective global immunisation strategy against COVID-19
We focused on characteristics that distinguish individual vaccine candidates from one another. We used a traffic-light system to signal the potential contributions of each candidate to achieving global vaccine immunity, with the colour red indicating high risks to achieving widespread immunity, amber indicating medium risk, and green indicating little or no risk. Appendix 1 outlines the methodology for constructing the dashboard, including the criteria for assigning a green, amber, or red light for each characteristic. Although specific datapoints and their corresponding traffic-light categorisations are subject to change as the pandemic response progresses, the dashboard will continue to provide a useful lens through which to analyse the key issues affecting the use of COVID-19 vaccines.
Figure 2Key characteristics of leading vaccine candidates with traffic-light system signalling potential for achieving global vaccine immunity
and can itself grant emergency use listing or prequalification for vaccines. †Clinical trial designs, including efficacy endpoints, differed for the various vaccine candidates; the efficacy figures might therefore not be perfectly comparable. Some of these results are interim analyses from phase 3 studies. Due to the emergence of new variants of the virus, the conditions under which trials take place vary, and not all vaccines are tested against the same variants. ‡These prices are the lowest the developers offered to any country or purchasing bloc; median prices for a range of countries are presented in figure 3. §The COVAX Facility has first right of refusal for a potential combined total of more than 1 billion doses in 2021 of vaccine candidates being developed by CEPI-funded companies: Biological E, Clover Pharmaceuticals, CureVac, Inovio, Moderna, Novavax, Oxford University/AstraZeneca, SK Biosciences, and the University of Hong Kong.
¶This was the result in the main efficacy analysis for participants receiving two standard doses, as specified in the protocol. The result in the out-of-protocol arm (a half dose followed by a standard dose) was 90%. This first-generation vaccine might offer less protection against a strain of SARS-CoV-2 first identified in South Africa. ||For the assignment of risk levels, we treated a single dose of a one-dose vaccine as equivalent to two doses of a two-dose vaccine. **One HIC (Hungary) has purchased 2 million doses, corresponding to 0·4% of all purchased doses; due to rounding, the figure presented in the dashboard is 0%. ††These interim phase 3 results have not been published in peer-reviewed journals; the figures were sourced from press releases by companies or researchers running the clinical trials. ‡‡The developer is also testing a two-dose version. §§This was the efficacy reported from a phase 3 trial in the UK; Novavax reported a lower efficacy level in a smaller phase 2b clinical trial in South Africa (49%). These results have not yet been published in peer-reviewed journals. ¶¶Sinovac and its research partners have reported a range of efficacy levels on the basis of phase 3 trials in Brazil (50%), Indonesia (65%), Turkey (91%), and the United Arab Emirates (86%), but none of these results have been published in peer-reviewed journals.
Development and production
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The world now needs more doses of COVID-19 vaccines than it has done for any other vaccine in history to inoculate enough people for global vaccine immunity.
but that has not been the case in this pandemic. As of Feb 3, 2021, there were 289 experimental COVID-19 vaccines in development, 66 of which were in different phases of clinical testing, including 20 in phase 3. Only five of these 66 vaccines—those developed by AstraZeneca in partnership with Oxford University, BioNTech in partnership with Pfizer, Gamaleya, Moderna, and Sinopharm in partnership with the Beijing Institute—have been authorised by stringent regulatory authorities (as per WHO criteria of such authorities
) or WHO (figure 2). Another five—from China, India, Kazakhstan, and Russia—have received approval or been authorised for emergency use by other regulatory agencies; some of the organisations developing these vaccines have submitted documentation to WHO for emergency use listing or prequalification, but these submissions are still under review.
Additional vaccines from Novavax and Johnson & Johnson are expected to be authorised on the basis of positive interim phase 3 results. Several vaccines have shown high levels of efficacy (ie, more than 70%) in clinical trials, although not all developers have published their results; most of the authorised vaccines have been shown to provide strong protection against hospitalisations and deaths due to COVID-19.
the urgent need to develop COVID-19 vaccines and scale up supply has inspired new ways of aiding research, development, and production activities and enlisting broad participation among private companies.
Governments and non-profit organisations have financed clinical trials, invested in the building and expansion of production facilities, and established contract manufacturing and distribution networks to enable the rapid roll-out of successful vaccines.
TablePublic and non-profit funding for the research, development, and production of leading vaccine candidates
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Before this pandemic, there were no existing networks of contract manufacturers for several of the leading vaccine candidates that feature novel technologies, including those relying on mRNA delivery platforms. Additionally, the volume of vaccines that is needed places pressure on global supply chains for inputs, such as glass vials, syringes, and stabilising agents.
and the relationships established between lead developers and contract manufacturers. A successful solution to the production bottleneck would probably require widespread technology transfer to enable the expansion of manufacturing capacity. Currently, few countries have the domestic capacity to rapidly produce COVID-19 vaccines on their own and instead will need companies to actively share knowledge, technology, and data with domestic manufacturers.
Some of the lead developers of COVID-19 vaccines have collaboration agreements with manufacturers in middle-income countries—AstraZeneca has such agreements with the Serum Institute of India, Fiocruz in Brazil, mAbxience Buenos Aires in Argentina, and Siam Bioscience in Thailand; Johnson & Johnson has an agreement with Aspen Pharmacare in South Africa; and Novavax with the Serum Institute of India—although the terms of these partnerships, including the extent to which the licensed manufacturers can negotiate their own supply arrangements with countries, are unclear.
Discussion
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In doing so, appeals to values of fairness and solidarity are common. By contrast, the widespread disregard for a global approach to vaccine allocation shown by national governments misses an opportunity to maximise the common good by reducing the global death toll,
supporting widespread economic recovery,
and mitigating supply chain disruptions.
More equitable distribution of COVID-19 vaccines would help contain the pandemic sooner, and thus minimise the risk of new variants of the virus arising, against which existing vaccines might be less effective.
In this Health Policy paper, we have stressed the interactions among the four dimensions involved in the global COVID-19 vaccination challenge. It is not enough to have new vaccines developed; they must be affordable, accessible, trusted, and, to maximise impact, used efficiently.
Governments and other vaccine purchasers must now decide which vaccines to procure, as well as how to secure funding for COVID-19 vaccines and vaccination programmes. To reach these decisions, government officials and partners in international organisations will need to assess the suitability of various vaccines for their respective health systems and populations—for example, in terms of availability, affordability, efficacy, and dosing and storage requirements.
Differences in product characteristics might become particularly salient in 2021, while vaccines remain in short supply. If additional vaccines are successful in clinical testing and developers meet their production targets, then COVAX could allocate vaccines, in part, on the basis of their suitability for local conditions. For instance, should single-dose vaccines that can be stored in refrigerators become available, which seems increasingly likely given the promising interim results by Johnson & Johnson, then these could be prioritised for distribution in low-income and middle-income countries that lack ultra-cold supply chains or national vaccine registries for two-dose regimens.
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Funders could also negotiate clear timelines for the recovery of research, development, and production costs by companies; for example, initial doses might be sold at higher prices in the first year in high-income countries and then sold closer to their marginal cost in subsequent years.
Determining these prices will require governments to audit the financial records of vaccine makers.
These allocation challenges also relate to production: conflicts over priority access to scarce vaccine doses could be made less acute with greater output (ie, with reduced scarcity of vaccine doses). To that end, WHO has called for member states, manufacturers, and other organisations to commit to sharing knowledge, intellectual property, and data related to COVID-19 health technologies, through the COVID-19 Technology Access Pool (C-TAP). Similarly, several countries have proposed to suspend World Trade Organization rules on intellectual property rights during the pandemic, suggesting that doing so could facilitate scale-up. Yet, as of February, 2021, no manufacturers of leading vaccine candidates have engaged with C-TAP, and the World Trade Organisation reform proposal has not gained traction.
In this domain too, the extensive public role in funding vaccine development potentially provides opportunities. Funders could encourage vaccine developers receiving public support to share their technologies and know-how systematically and widely to expand global production. Funders could also work with developers to alleviate supply chain constraints and accelerate the scaling up of production. To the extent that international control of COVID-19 is regarded as a priority for individual countries, governments might have an incentive to exercise these levers.
Equally, vaccine manufacturers should aim for maximum transparency and scrutiny of their clinical trial data to build public trust. Regulatory bodies safeguard public health by assessing whether the benefits of pharmaceuticals outweigh their risks. Regulatory decisions and their rationale should be clearly communicated to the public to provide reassurance that authorised products are safe and efficacious. It is in the interest of vaccine developers to seek approval or emergency use authorisation from a stringent regulatory body or WHO: only vaccines that have gone through one of these regulatory pathways will be eligible for purchase through COVAX or through funds made available by major development banks.
MS-K reports receiving grants from Health Action International, outside the submitted work. AJP is Chair of the UK Department of Health & Social Care’s Joint Committee on Vaccination & Immunisation (JCVI) but does not participate in policy advice on coronavirus vaccines. He is also a member of the WHO Strategic Advisory Group of Experts (SAGE) and Chief Investigator of the clinical trials for vaccine candidate AZD1222 against COVID-19, sponsored by the University of Oxford. The University of Oxford has entered into a partnership with AstraZeneca on vaccine development for candidate AZD1222. The trials are funded by UK Research and Innovation (MC_PC_19055), Engineering and Physical Sciences Research Council (EP/R013756/1), the Coalition for Epidemic Preparedness Innovations (CEPI), the National Institute for Health Research (NIHR), the NIHR Oxford Biomedical Research Centre, and the German Center for Infection Research (DZIF). HJL reports receiving grants from Merck and GlaxoSmithKline, and honoraria from Merck (for serving on a vaccine confidence advisory board) and GlaxoSmithKline (for speaking at staff training sessions). MJ reports receiving grants from the Bill & Melinda Gates Foundation (INV-016832), European Commission’s Horizon 2020 programme (101003688), and National Institute for Health Research (NIHR200929, NIHR200908), outside the submitted work. All other authors declare no competing interests.
OJW, KCS, and MJ conceived of and designed the manuscript. OJW and MS-K collected and analysed the data. OJW drafted the manuscript. All authors had full access to all the data in the study, contributed to revisions to the article, and had final responsibility for the decision to submit for publication.
