Researchers from Yale School of Public Health used a previously published model of a COVID-19 vaccination program to quantify the speed-versus-efficacy tradeoff of vaccination deployment.
The model accounted for transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19 disease severity, and recovery or vaccination leading to protective immunity. According to the authors’ analysis, a 2-dose vaccination strategy would impose steep clinical and epidemiologic costs in the context of ongoing pandemic response.
Depending on the duration of protection conferred, a single-dose vaccine with 55% effectiveness may confer greater population benefit than a 95%-effective vaccine requiring two doses.
Authors from the University of Washington and Fred Hutchinson Cancer Research Center suggest that speed is essential for controlling the COVID-19 pandemic and offer four rationales supporting their conclusion:
- Doubling the vaccine coverage with a single dose compared with a 2-dose regimen will accelerate pandemic control because even lack of complete protection on an individual level is likely to lower transmission rates enough to stop epidemic growth;
- Providing effective protection for as many people as possible is more ethical because it distributes the scarce commodity more justly;
- A single-dose vaccine approach could mitigate the higher incidence of many vaccine-associated adverse events seen with the second dose;
- And administering a vaccine that is only partly protective may reduce risky behavior such as doffing masks or eliminating social distancing.
Researchers from Stanford University developed a decision analytic cohort model to estimate direct benefits of vaccination against COVID-19 under alternative strategies for dose allocation. First, they analyzed a fixed strategy based on the current U.S. model of two doses, timed about one month apart.
Second, they analyzed a flexible strategy that would reserve 10% of the supply for second doses during the first three weeks, 90% during each of the next three weeks, and 50% thereafter.
They estimate that the flexible strategy would result in an additional 23% – 29% of COVID-19 cases averted compared with the fixed strategy.
In both scenarios, 24 million people received at least one dose of the vaccine by week 8, whereas 2.4 million additional people received two doses of vaccine in the flexible strategy because million more received an initial dose during the first three weeks.
According to the researchers, these findings suggest that vaccinating more people as soon as possible using a flexible approach could increase the benefits of vaccines while enabling most recipients to receive second doses on schedule.
Global strategies for allocation of vaccine resources
With the aim of mapping and planning vaccine production efforts, the Coalition for Epidemic Preparedness Innovations (Oslo, Norway) surveyed vaccine manufacturers and found production capacity to lie between 2 and 4 billion doses by the end of 2021, presuming clinical trials are successful.
Airfinity (London, UK), a market analytics firm, projected that only 1 billion doses could become available by the end of 2021 after adjusting for vaccine developers’ characteristics and chances of success [12]. Despite the efforts aimed at scaling up manufacturing capacity, vaccines will be scarce, especially in the first phases of deployment.
Wealthy countries have already signed purchase commitments for more than 2 billion doses [12], limiting equitable access and international efforts for global allocation appear unsuccessful so far. Three main international allocation models have been proposed.
In the first model, the WHO suggested a population-proportional distribution model, starting with 3% of the population receiving vaccines and continuing with allocation until all countries have vaccinated 20% of their population [5].
In the second model, the WHO suggested allocation to be based on the number of frontline workers, incidence of comorbidities and proportion of the population over 65 years of age [5].
These two models present limitations. A population-proportional allocation system fails to consider differences in mortality and economic effects of COVID-19 in different countries. The second proposal may penalise low and middle-income countries which often have a younger population and fewer healthcare workers per capita [13].
The third model, the Fair Priority Model, strives to address some of the aforementioned limitations by using health and socioeconomic metrics to gauge and allocate vaccine doses based on quantified effects on health and economies [13].
Transmission rates, standard expected years of life lost averted per dose of vaccine, absolute improvement in gross national income and reduction in the absolute size of the poverty gap per vaccine dose are used as allocation criteria. The WHO and World Bank (DC, USA) could play a crucial role in defining a framework to calculate these variables. Nevertheless, the Fair Priority Model is heavily dependent on the integrity and transparency in data reporting and analysis.
A possible solution to ensure further cooperation and transparency could be to create an international multi-tasking platform coordinating contracts between pharmaceutical companies, contractors, distributors, governments and donors. The platform could be supervised by an international entity, such as the WHO, and it would work at its full potential if funding provisions from governments and other donors could be allocated exclusively to the companies that partake in the platform.
For the pharmaceutical companies involved, partaking into the platform ensures that their capabilities are saturated and that they have a clear timeline of commitments. If their candidate fails, then they would be automatically enrolled as a vaccine manufacturer that can license-in a successful vaccine compatible with their production capabilities.
For governments, allocating funds to a platform with a wide vaccine portfolio decreases the risks of failure connected to engaging only with few vaccine producers whose candidates may fail.
Scaling-up manufacturing capabilities
As promising data on vaccine efficacy is released, vaccine developers are rushing to build manufacturing capacity. Based on the vaccination guidelines suggested by the WHO (Geneva, Switzerland), the initial vaccination strategy requires 4265 Mn doses of vaccine to protect at-risk populations [5].
It took 9 years to take the global production capacity of pandemic influenza vaccines from 1500 Mn doses in 2006 to 6400 Mn doses in 2015 [6]. Reaching similar results with SARS-CoV-2 candidates in a much shorter timeframe requires a considerable manufacturing effort, regardless of the vaccine type.
Synthetic manufacturing methods used for mRNA and DNA vaccines offer a streamlined manufacturing line and favourable characteristics, such as low batch-to-batch variability and more agile equipment; however, these methods have never been used to produce vaccines at large scale.
On the other hand, cell-culture-based approaches used for live-attenuated virus vaccines, inactivated and subunit vaccines can rely on a much longer history of good manufacturing practices. However, cell-culture-based approaches entail several cell culture expansion and purification steps which are time consuming and require large-scale equipment.
No single vaccine approach is currently emerging as a winner and it is likely that multiple safe vaccines will be approved. In fact, the diversity in vaccine technologies may provide the potential for scalable production required for widespread vaccine deployment [7].
The large demand for doses will likely require vaccine manufacturers to engage in collaborations and partnerships. In an initial call for collaboration, the WHO encouraged key stakeholders to voluntarily pool knowledge, data and intellectual property in the COVID-19 Technology Access Pool [8].
The initiative was received with resistance by the pharmaceutical industry, especially in the field of biologics and vaccine manufacturing where traditionally much of the knowhow is never publicly shared nor contained in patents [9], as it represents competitive advantage and is the result of considerable R&D investment.
However, with increasing pressure on development pipelines, secrecy may hinder progress and some companies have started to seek knowledge transfer and sharing. Six biopharmaceutical companies working on monoclonal antibody candidates were recently granted permission by the US Department of Justice to exchange ‘technical information’ on each other’s manufacturing processes and platforms under antitrust law [10].
Such knowledge transfer agreements may also occur among vaccine firms. It is likely that several manufacturers and developers will engage in various forms of licensing deals to produce enough doses of the candidates that prove efficacious. Moreover, several, if not all, of the funding provisions and advanced purchase commitments undersigned by various countries and organisations may already contain conditions that encourage knowledge sharing [11].
Overall, policy makers should facilitate and encourage knowledge sharing to produce vaccines as broadly and efficiently as possible.
reference link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737565/
More information: A. David Paltiel et al. Speed Versus Efficacy: Quantifying Potential Tradeoffs in COVID-19 Vaccine Deployment, Annals of Internal Medicine (2021). DOI: 10.7326/M20-7866
Ruanne V. Barnabas et al. A Public Health COVID-19 Vaccination Strategy to Maximize the Health Gains for Every Single Vaccine Dose, Annals of Internal Medicine (2021). DOI: 10.7326/M20-8060
Ashleigh R. Tuite et al. Alternative Dose Allocation Strategies to Increase Benefits From Constrained COVID-19 Vaccine Supply, Annals of Internal Medicine (2021). DOI: 10.7326/M20-8137
